Evidence Table 6Observational studies of safety and adverse events in patients with schizophrenia

Author, year
Country
Data sourceProspective Retrospective UnclearSampling frameExposure periodInterventions mean dosePopulationAge
Gender
Ethnicity
Exposed
Eligible
Selected
Withdrawn Lost to fu AnalyzedEffectiveness outcomesSafety outcomesComments
Controlled studies
Advokat, 2004
United States
Hospital charts and medical records from the Eastern
Louisiana Mental Health System
RetrospectiveSeptember 1996 through September 2001NROlanzapine: 20.6mg/day
Risperidone: 5.3mg/day
Quetiapine: 320.6mg/day
Clozapine: 375mg/day
Patients reporting initial baseline value of 35 or greater on the Brief Psychiatric Rating Scale (BPRS) and had at least 3 successive monthly BPRS ratingsOlanzapine/Risperidone/Quetiapine/Clozapine
Mean age (years): 39.8/41.2/43.3/38.7
%male: 37/22/36/29
%African-American: 50/47/45/71
NR/NR/100NR/NR/100Maximum daily dosages
28 of 46 patients on olanzapine received 15mg or less per day as max dose
21 of 36 patients on risperidone received 4mg or less per day as max dose
8 of 11 patients on quetiapine received 400mg or less per day as max dose
7 of 7 patients on clozapine received 450mg or less per day as max dose
Average Length of stay in hospital
Olanzapine: 332 days
Risperidone: 376 days
Quetiapine: 558 days
Clozapine: 583 days
20% or more change from baseline on BPRS
Olanzapine: 33 of 46 ( 72%) patients
Risperidone: 16 of 36 (44%) patients
Quetiapine: 4 of 11 (36%) patients
Clozapine: 5 of 7 (71%) patients
Response latency
Olanzapine: 1.67 months
Risperidone: 1.47 months
Quetiapine: 2.00 months
Clozapine: 2.75 months
NR
Advokat, 2003Eastern Louisiana Mental Health SystemRetrospective1995–20015 yearsolanzapine 332 days
risperidone 376 days
quetiapine 558 days
clozapine 583 days
Schizoaffective/Bipolar Type, Paranoid
Schizophrenia, or Schizophrenia
Undifferentiated
Mean age=40.6 years
31% male
50% Africa American
398/100/100NR/NR/100length of hospitalization:
olanzapine (n=18) vs risperidone (n=9) = 634 days vs 1017 days, p=0.038
>20% decline from baseline in BPRS score:
olanzapine = 33/46 (72%)
risperidone = 16/36 (44%)
clozapine = 52/59 (88%)
clo vs ris, p<0.01; ola vs ris, p=0.012; clo vs ola, p=0.034
responders that retained or improved their BPRS scores:
olanzapine vs risperidone, NS
Latencies from responders:
olanzapine vs risperidone = 1.67 vs 1.47 months
NR
Agelink, 2001
Germany
Evangelical Hospital
Gelsenkirchen, Germany
RetrospectiveMean: 14.1 daysNRamisulpride: 400 mg/day, olanzapine: 20 mg/day, sertindole: 12 mg/day, clozapine: 100 mg/dayMedication-free inpatients with schizophreniaMean age: 33.7 years
68.8% Male
Ethnicity NR
NR/NR/510/0/51NRclozapine, olanzapine, sertindole had a prolonged mean frequency-corrected QTc times; P<0.05
HRr at endpoint: A: 77.2 vs O: 84.6 vs S: 88.7 vs C: 95.9
CVr at endpoint: A: 3.9 vs O: 3.9 vs S: 5.2 vs C: 2.3
Akkaya 2007
Turkey
Medical record review: Psychiatry Retrospective
Outpatient Clinic of Uludag
University Medical Faculty
January 1998 to October 2005Risperidone/Haloperidol/Olanzapine

Mean duration of treatment (d):
430.7±536.7/761.5±836.7/754.5±818.9
Risperidone/Haloperidol/Olanzapine

Mean dose (mg): 3 ±1.4/5.4±5.1/11.7±5.4
Patients diagnosed with schizophrenia and placed on drug treatmentRisperidone/Haloperidol/Olanzapine

Age (y): 34.5±13.5/34.6±12.5/32.5±14.8
Gender (% male): 57.1/58.2/60
Ethnicity: NR
NR
407
274
NR
NR
189 (63 risperidone, 91 haloperidol, 35 olanzapine)
Risperidone/Haloperidol/Olanzapine

Rates of discontinuation (%) over 18 months
68.3/51.6/54.3
Relapse under treatment (%)
No: 81/68.1/65.7
Yes: 19/31.9/34.3
Relapse resulting in hospitalization (%)
No: 33.3/44.6/41.7
Yes: 66.7/55.2/58.3
Reason of treatment discontinuation (%)
Compliance issues: 74.6/72.5/60
Side effect: 4.8/5.5/8.6
Relapse: 4.8/11/5.7
Hospitalization: 1.6/3.3/8.6
Treatment continued: 14.3/7.7/17.1
Risperidone/Haloperidol/Olanzapine

Side effects that caused treatment discontinuation (authors do not report if this figure is n or %)
EPS: 0/5/2
Prolactin increase: 2/0/0
Weight gain: 0/0/1
Sedation: 1/0/0
Al-Zakwani, 2003
United States
Multicenter, United StatesRetrospective24 months18 monthsDoses not reported. Interventions-Typical Antipsychotics: chlorpromazine, haloperidol, thioridazine, perphenazine, other; Atypical Antipsychotics: risperidone, olanzapine, quetiapine, clozapinePsychosis, neurotic, personality and sexual disorders, drug/alcohol dependence, psychological malfunction arising from mental disorders, depressive disorder, childhood emotional disturbance/developmental delays, mental retardation/Alzheimer’s/Parkinson’s diseasesMean age: 38.5 years
59% Male
Ethnicity NR
2710/833/469NR/NR/469Typical Antipsychotics:
# dose adjustments: 14(16.5%)
# treatment augmentation: 1(1.2%)
# requiring treatment switch: 11(12.9%)
# receiving mixed therapy: 1(1.2%)

Atypical Antipsychotics:
# dose adjustments: 128(30.4%)
# treatment augmentation: 3(0.8%)
# requiring treatment switch: 70(18.2%)
# receiving mixed therapy: 7(1.5%)
NR
Ascher-Svanum, 2004
Faries, 2005
USA
U.S. Schizophrenia Care and Assessment Program (US SCAP)ProspectiveJuly 1997 to 2003One yearOlanzapine
Risperidone
DSM-IV criteria for schizophrenia, schizoaffective, or schizophreniform disorder;
≥ 18 years; and understood and provided informed consent.
Excluded if participation in a controlled clinical drug trial in past month
Age at enrollment, Olanzapine 43.5 Risperidone 39.3
Male, Olanzapine 62.9% Risperidone 54.5%
Ethnicity
White Olanzapine 52.8% Risperidone 49.1%
Black Olanzapine 41.5% Risperidone 39.1%
Other Olanzapine 5.7% Risperidone 11.8%
NANR/NR/Olanzapine n = 159
Risperidone n = 112
Adherent group (n = 271)
Hospitalization rates risperidone 24.1% vs. olanzapine 14.4% P = 0.040
Hospitalization days risperidone 14.5 days vs. olanzapine 9.9 days P = 0.035.
Adherent and non-adherent groups combined (n = 516)
Hospitalization rates risperidone 31.5% vs. olanzapine 23.6% P = 0.045
Hospitalization days risperidone 17.6 days vs. olanzapine 19.1 days P = 0.755.

Odds of staying on monotherapy during the 1-year period (versus initiating polytherapy) (Faries 2005)
Olanzapine versus quetiapine: OR 2.08 (95% CI 1.30, 3.31)
Olanzapine versus risperidone: OR 1.36 (95% 1.01, 1.84)
NR
Ascher-Svanum 2008
US (21 sites in multiple states)
Data from a randomized, open- label study of the cost effectiveness of olanzapine, risperidone, and typical antipsychotics. Twenty sites in the US.RetrospectiveMay 1998–September 2002One yearolanzapine 13.3 mg
risperidone 4.85 mg
typical antipsychotics: perphenazine, haloperidol, loxapine, thiothixene, fluphenazine, trifuloperazine, mesoridazine, thioridazine, chlorpromazine, molindone
18 years of age or older, DSM-IV criteria for schizophrenia, schizoaffective or schizophreniform disorders, minimum scoreof 18 on BPRS.Mean age 43 years
63% male
54% white, 34% African American, 12% other race/ethnicity
664
664
648 (222 olanzapine, 217 risperidone, 209 typical antipsychotics)
None reported
None reported
648
Mean time (SD) to all-cause medication discontinuation:
Olanzapine: 277.2 days (123.9); p<0.001 vs typical antipsychotics; p<0.001 vs risperidone;
Risperidone: 231.9 days (142.2)
Typical antipsychotics: 193.5 days (137.9)
Perphenazine: 277.2 days (123.9)
One-year survival rates (SD):
Olanzapine: 55.3% (3.6%); p=0.007 vs risperidone
Risperidone: 46.8* (3.5%)
Typical antipsychotics: 31.7% (3.3%); p <0.001 vs olanzapine; p=0.002 vs risperidone
Perphenazine: 30.8% (6.8%); p<0.001 vs olanzapine; p=0.060 vs risperidone
NA
Barak, 2004
Israel
Abarbamel Mental Health Center, Bat-YamRetrospectiveJanuary 1998 to December 20025 yearsclozapine 445mg for 575 days
olanzapine 17.8mg for 492 days
risperidone 4.6mg for 466 days
Schizophrenia or schizoaffective disorder with attempted suicide in the 4 weeks preceding admissionsMean age=39.1 years
84.7% male
Ethnicity: NR
68000/4486/378NR/NR/378NRsuicide group vs control group
exposed to second generation antipsychotics: 16% vs 37%, p=0.0001

protective effect: OR (p, 95% CI)
overall: 3.54 (p=NR, 2.4–5.3)
risperidone: 3.16 (p=0.001, 1.9–5.3)
olanzapine: 1.76 (p=0.02, 1.2–3.3)
Barner, 2004
United States
Database: Central Texas
Veterans Health Care System
RetrospectiveDuration of treatment NR.
Mean number of persistent days (total number of continuous days the patient took an antipsychotic agent without a gap, I.e. a 15-day lapse in therapy):
AAPs: 3.9–5.6 months
Typical APs: 4.7–7.3 months
NRAny AAP or typical AP, dose and duration not reportedIncluded subjects aged 18+ who had not received a typical AP or AAP 6 months prior to the dispensing of a typical AP or AAP, and had not been diagnosed with DM or used an antidiabetic drug 12 months before being prescribed a typical AP or AAP.Mean age 59.4
94.3% male
69.9% white
6735
3469
3469
NR
NR
3469
NRFrequency of new-onset diabetes mellitus among patients taking AAPs:
AAP group (n=2477) 7.2% (ns)
Typical AP group (n=992) 7.0% (ns)
Risperidone 7.5% (ns)
Quetiapine 5.8% (ns)
Olanzapine 6.4% (ns)
Adjusted OR of new-onset diabetes mellitus (95% CI):
Olanzapine 0.976 (0.594–1.605)
Quetiapine 1.149 (0.531–2.485)
Risperidone 0.926 (0.544–1.579)
Dose and duration of treatment are not controlled for in this analysis
Bitter, 2005
Africa, the Middle East, Asia, Central and Eastern Europe, Latin America IC-SOHO Study (6-month data) Hostile/aggressive behavior outcomes
same as Dossenbach 2004same as Dossenbach 2004same as Dossenbach 2004same as Dossenbach 2004same as Dossenbach 2004Subset of patients who sustained monotherapy and had hostile/aggressive outcome data available at 3-and 6-monthsMean age=35.2 years
54% male
Ethnicity NR
7655/5828/3135NR/NR/3135Change in proportions of patients with hostile/aggressive behavior from baseline to 6 months:
Clozapine: −16.8%
Olanzapine: −23.1%
Quetiapine: −18.3%
Risperidone: −22.7%

Odds ratios for improvement of hostility over time (95% CI):
Risperidone vs clozapine: 1.83 (1.05, 3.20)
Olanzapine vs clozapine: 1.67 (1.01, 2.75)
NR
Bond, 2004
United States
A psychiatric rehabilitation agency and four community mental health centers.ProspectiveMarch 1999 to January 20019 monthsOlanzapine 12.9 mg
Risperidone 5.4 mg
Schizophrenia or schizoaffective disorderMean age=40.8 years
59% male
45% Caucasian; 42% Africa American; 3% other
551/124/90NR/NR/90work outcomes: olanzapine (n=39) vs risperidone (n=27) vs first-generation anti-psychotics (n=24) paid employment at any time; 29(74%) vs 17(63%) vs 13(54%), NS integrated employment at any time: 16(41%) vs 8(30%) vs 8(33%), NS

second generation vs first generation:
vocational activities: 76% vs 50%, p<0.05
increase in vocational activities: higher vs lower, p<0.001
monthly rate of paid employment: higher vs lower, NS
monthly rate of integrated employment: greater vs lower, p=0.001
NR
Brown, 2005
United States
Review of charts of VA patientsRetrospectiveJune 2001 to March 2003NRZiprasidone
Olanzapine
Schizophrenia or other psychosesMean age (years): Ziprasidone=47.3; Olanzapine=53.9
Gender:
Ziprasidone=90.9% male; Olanzapine=96.1% male
Ethnicity: NR
NR/NR/191NR/NR/191Weight changes
Patients gained an average of 3.9kg on olanzapine (P<0.001)
Patients lost on average 1.5kg on ziprasidone (P>0.05)
Patients switched from olanzapine to ziprasidone lost an average of 3.4kg over the course of therapy (P=0.002)

Metabolic changes
Olanzapine was associated with an 8% increase in total cholesterol (P=0.01), an 11% increase in LDL, a 4% decrease in HDL, a 27% increase in triglycerides (P=0.05) and a 6% increase in HbA1c (P<0.05)
Ziprasidone was associated with a 7% reduction in total cholesterol, a 14% decrease in LDL, an 8% increase in HDL, a 7% decrease in triglycerides and a 9.4% reduction in HbA1c
NR
Buse, 2003
United States
AdvancePCS IncRetrospective≥2 yearsNRClozapine: 183.1 mg/day
Olanzapine: 5.1 mg/day
Quetiapine: 79.9 mg/day
Risperidone: 1.2 mg/day
Haloperidol: 2.5 mg/day
Thioridazine: 43.9 mg/day
SchizophreniaMean age: 52 years
63% male
5,816,473
58,751
58,751
Withdrawn=N/A (retrospective)
Lost to follow-up=N/A (retrospective)
Analyzed=58,751
Risk of Diabetes Mellitus:
olanzapine: P=0.479
clozapine: P=0.496
quetiapine: P=0.033
haloperidol: P=0.040
Hazard ratio of developing diabetes comparing antipsychotics to haloperidol group:
olanzapine:
risperidone: P=0.479
quetiapine: P=0.040
clozapine: P=0.496
Caro, 2002
Quebec
Database: Regie de l’Assurance
Maladie du Quebec
Retrospective1/1/97 to 12/31/99NROlanzapine
Risperidone
Psychotic disorders ≥ 1 prescription for olanzapine or risperidoneMean age NR
47.2% male
Race NR
NR
34,692
33,946
Olanzapine=19,153
Risperidone=14,793
NR
NR
33,946
NRDiabetes
Olanzapine=319/17
Risperidone=217/16
p=0.43 (Cases/rate per 1000 patient years)
Castro 2007
Brazil
Chart review: Institute of Psychiatry, Universidade de Sao
Paulo
RetrospectiveNR12/1/97-12/31/99NRPatients with schizophrenia who were discharged on a regimen of either haloperidol, risperidone or clozapine

Exclusion criteria: patients discharged on two or more antipsychotics, patients with another axis 1 disorder and diagnosis of neurological disorders
Haloperidol/Risperidone/Clozapine

Mean age: 38.28±10.17/37.59±11.72/35.55±9.48
Male (n): 17/10/21
Ethnicity: NR
NR
NR
96 (43 haloperidol, 22 risperidone, 31 clozapine)
NR
NR
96
Haloperidol/Risperidone/Clozapine

Mean time to hospital readmission (d): 395±318 (range 54–1015)/284±200 (range 6–596)/264±157 (range 88–427)
Median time to hospital readmission (d):286/271/303
*No significant difference in time to rehospitalization between groups (ANOVA F=0.66; df=2; p=0.53)

Mean length of follow-up for patients who were not readmitted (d): 718±483 (range 14–1095)/879±421 (range 22–1095)/1053±210 (range 26–1095)

Percentage of patients remaining non-hospitalized:
12 months: 84/73/90
24 months: 79/59/84
36 months: 74/59/84

Rehospitalization rates (%):
12 months: 16/27/10
24 months: 21/41/16
36 months: 26/41/16
*No significant difference in rehospitalization rates between treatment groups; P-value=NR
NR
Citrome 2004
US (New York State)
Integrated Research Database, containing patient information and drug prescription information for every inpatient within the 17 adult civil facilities of the NY State psychiatric hospital systemRetrospectiveJanuary 1, 2000–December 31, 2002Case group: mean 121 + 60.9 days
Control group: mean 133 + 55 days
clozapine
risperidone
olanzapine
quetiapine
Mean doses not reported
Case group: those who received new prescription of antidiabetic medication. Required to have at least a 30-day period of hospitalization before the start of the prescription.
Control group: Those who did not receive a prescription of antidiabetic medication, matched to those in case group on calendar year, then length of stay, then race, then age group, then diagnosis.
Case group:
Mean age 43.3 years (SD 11.4)
61% male
32% white

Control group:
Mean age 43.7 years (SD 12.8)
71% male
32% white
13,611
8,461
1,629
NR
NR
1,629
Adjusted odds ratio (95% CI) for development of diabetes vs typical antipsychotic use:
Clozapine only: 2.06 (1.07, 3.99)
Olanzapoine only: 1.57 (0.87, 2.82)
Quetiapine only: 3.09 (1.59, 6.03)
Risperidone only: 1.50 (0.81, 2.79)
More than one atypical antipsychotic: 2.86 (1.57, 5.20)
Conley, 1999
United States
Record review: Maryland state psychiatric facilitiesProspective3/14/94 to 12/31/95NRClozapine
Risperidone
SchizophreniaMean age=40.4
60.5% male
Race NR
NR
NR
124
(clozapine=49, risperidone=75)
NR
NR
unclear
NRHospitalization
Readmission rates (% patients)
Year 1=13% vs 17%; p=NS
Year 2=13% vs 34%; p=NS
Mean time to readmission (days)=360 vs 319
Cooper, 2005
Canada
Database: Quebec health insurance database and Quebec database for hospitalizationsRetrospectiveJuly 1, 1996 through August 31, 20061 yearOlanzapine
Risperidone
SchizophreniaAge: 8% 0–24 years; 50% 25–44 years; 32% 45–64 years; 10% 65 years and over
Gender: 57% male
38,048/6,405/6,405NR/NR/6,405Mean days of use before discontinuation
olanzapine=233
risperidone=142
(60.5% of individuals discontinued use of initial treatment prior to one-year)
Concomitant use
Of those who stayed on their initial treatment for at least one year:
738 (47.3%) of olanzapine users and 435 (48.5%) of risperidone users received at least one concomitant antipsychotic prescription during treatment
NR
Cooper, 2007
Canada
Database: Quebec health insurance board and Quebec registry of hospitalizationsRetrospectiveJanuary 1, 1997 to August 31, 19991 yearLow intensity:
Olanzapine= ≤9.7mg/day; Risperidone= ≤1.9mg/day; Clozapine= ≤300mg/day; Quetiapine= ≤100mg/day
Medium intensity:
Olanzapine= >9.7mg/day but ≤10.0mg/day;
Risperidone= >1.9mg/day but ≤4.0mg/day;
Clozapine= >300mg/day but ≤425mg/day;
Quetiapine= >100mg/day but ≤300mg/day
High intensity
Olanzapine= >10mg/day; Risperidone= >4mg/day;
Clozapine= >425mg/day; Quetiapine= >300mg/day
SchizophreniaAge: 27% 0–34 years; 63% 35–64 years; 10% 65 years or older
Gender: 57% male
Ethnicity: NR
NR/NR/6662NR/NR/6662Persistence
Individuals started on clozapine were more likely to be persistent than those on olanzapine, however those on olanzapine were more likely to be persistent than those on risperidone
Individuals who received a dosage in the low or medium intensity were more likely to be persistent than those receiving the high intensity dosage
NR
Coulter, 2001
International
Database: Uppsala Monitoring Centre in SwedenUnclearNRNRClozapine
Olanzapine
Quetiapine
Risperidone
NRNR
NR
NR
NR
NR
NR
NR
NR
Reports analyzed: Clozapine=24730, Olanzapine=6,135, Quetiapine=709, Risperidone=10,746
NRCardiomyopathy or myocarditis (# cases/%)
Clozapine=231/0.9%
Olanzapine=8/0.1%
Quetiapine=2/0.3%
Risperidone=16/0.1%
de Haan, 1999
Netherlands
University of AmsterdamRetrospective7.3 months averageNRclozapine: NR
other drugs: NR
Schizophrenia or schizoaffective disorder, schizophreniform disorderMean age: 20.9 yearsNR/NR/121Withdrawn=N/A (retrospective)
Withdrawn=N/A (retrospective)
Analyzed=121
% of patients experiencing an emergence of increase of obsessions after treatment:
C: 20.6% vs other drugs: 1.3%; (P<.01)
NR
de Haan, 2002
Netherlands
Academic Medical Center, University of AmsterdamProspective6 weeksNROlanzapine(N=39): 14.2mg
Risperidone(N=23): 4.1mg
N=113
Schizophrenia, 15% OCD disorder, drug class naïve
Mean age: 22.4 yearsNR/113/113NR/NR/62Yale-Brown Obsessive Compulsive Scale (YBOCS) Mean Scores:
At Admission: R: 2.4 vs O: 2.4
At Endpoint (6 weeks): R: 2.2 vs O: 1.9
NR
de Leon, 2004
United States
Clinical Research Center, Norristown State Hospital, NorristownRetrospective16 weeksNRAll patients switched from 4 weeks on 10 mg/day of haloperidol, to 100, 300, 600 mg/day clozapineSchizophreniaMean age: 45.5 years
54% Male
85.5% Caucasian
14.5% African-American
NR/NR/40NR/NR/35NRWithin-subject correlation of prolactin levels:
C: 0.32 vs H: 0.75
Dinakar, 2002
United States
Rockland Psychiatric Center, NYRetrospective3 monthsNRAt endpoint:
olanzapine: 52.75
risperidone: 52.53
SchizophreniaMean age: 55.5 years
Gender and Ethnicity NR
NR/79/790/0/79BPRS scores: baseline vs endpoint
O: 67.03 vs 52.75
R: 62.70 vs 52.53
NR
Dolder, 2002
United States
Database: VA San Diego Healthcare SystemRetrospectiveNR12 monthsHaloperidol 8mg/day
Perphenazine 12mg/day
Risperidone 4mg/day
Olanzapine 12.5mg/day
Quetiapine 400mg/day
Schizophrenia, schizoaffective disorder, mood disorder with psychotic features, or psychosis not otherwise specifiedAge=49.7
89.9% male
Ethnicity (%)
 Caucasian=61.8
 African American=18.4
 Hispanic=9.4
 Other=5.5
629/NR/288Withdrawn=N/A (retrospective)
Withdrawn=N/A (retrospective)
Analyzed=288
Adherence Rates-cumulative mean gap ratio
Those treated with atypical antipsychotics had significantly smaller gaps in therapy compared to those treated with typical antipsychotics at 6-months (p=0.001) and at 12-months (p=0.001).
Olanzapine had a significantly lower gap ratio compared to haloperidol at 6-months (p=0.008), no other significant differences between individual medications was observed at either 6-months or 12-months.
Adherence Rates-compliant fill rate
Those treated with atypical antipsychotics had significantly higher adherence rates at 6-months compared to those treated with typical antipsychotics (p=0.05), at 12-months the trend was similar, though not at the significant level.
NR
Dossenbach et al, 2004
27 countries in Africa, Asia, Europe, Central and South America and the Middle East
IC-SOHO Study (6 month data)
Prospectively collected, multicenter study dataProspective6 mos (interim data - planned exposure 3 yrs)NRMean doses at 6 mos:
olanzapine 10.9 mg/day (SD 4.8)
quetiapine 339.5 mg/day (SD 188.9)
risperidone 4.0 mg/day (SD 2.1)
haloperidol 12.2 mg/day (SD 9.3)
SchizophreniaMean age 35.5 yrs (SD 12.2)
54% male
Ethnicity NR
7658/NR/5833NR/NR/unclear; according to the text “as a result of missing data, the number of patients in each subgroup may differ for each comparison”CGI-Severity of Illness Scale score, mean change from baseline at 6 months:
Overall: O −1.44 (SE 0.04) v Q −1.02 (SE 0.09) v R −1.24 (SE 0.05) v H −0.87 (SE 0.08)
Statistically significant difference (p≤0.001) for the following comparisons: O v Q, R, & H; R v H

Positive: O −1.44 (SE 0.05) v Q −1.01 (SE 0.10) v R −1.27 (SE 0.06) v H −1.07 (SE 0.09)
Statistically significant difference (p≤0.001) for the following comparisons: O v Q, R, & H

Negative: O-1.21 (SE 0.04) v Q −0.82 (SE 0.09) v R −0.98 (SE 0.05) v H −0.65 (SE 0.08)
Statistically significant difference (p≤0.001) for the following comparisons: O v Q, R & H; R v H

Depressive: O −1.11 (SE 0.04) v Q −0.83 (SE 0.09) v R −0.91 (SE 0.05) v H −0.67 (SE 0.08)
Statistically significant difference (p≤0.001) for the following comparisons: O v Q, R & H

Cognitive: O −1.05 (SE 0.04) v Q −0.61 (SE 0.09) v R −0.83 (SE 0.05) v H −0.54 (SE 0.08)
Statistically significant difference (p≤0.001) for the following comparisons: O v Q, R & H; R v H
Weight change: significantly higher with olanzapine use compared to all other interventions (p<0.0001)
O 2.57 kg (SE 0.21)
Q 0.58 kg (SE 0.44)
R 1.49 kg (SE 0.26)
H 0.73 (SE 0.40)
Data on pts remaining on monotherapy or switching therapies not abstracted
Dossenbach et al, 2005
Dossenbach 2006 for sexual dysfunction results
27 countries in Africa, Asia, Europe, Central and South America and the Middle East
IC-SOHO Study (12 month data)
Same as Dossenbach 2004Same as Dossenbach 200412 monthsNRSame as Dossenbach 2004Schizophreniasame as Dossenbach 2004same as Dossenbach 20041007/225/3551 (from Figure 1 in text)CGI-Severity of Illness Scale score, least squares mean change from baseline at 12 months:
Overall: O −1.80 (SE 0.04) v Q −1.62 (SE 0.06) v R −1.39 (SE 0.11) v H −1.04 (SE 0.11)
Statistically significant difference (p≤0.001) for the following comparisons: O v Q, R, & H; R v H

Positive: O −1.74 (SE 0.05) v Q −1.64 (SE 0.06) v R −1.44 (SE 0.12) v H −1.16 (SE 0.11)
Statistically significant difference (p≤0.001) for the following comparisons: O v H; R v H

Negative: O −1.58 (SE 0.05) v Q −1.38 (SE 0.06) v R −1.25 (SE 0.12) v H −0.88 (SE 0.11)
Statistically significant difference (p≤0.001) for the following comparisons: O v R & H; R v H

Depressive: O −1.38 (SE 0.05) v Q −1.21 (SE 0.06) v R −1.06 (SE 0.12) v H −0.73 (SE 0.11)
Statistically significant difference (p≤0.001) for the following comparisons: O v R & H; R v H

Cognitive: O −1.34 (SE 0.05) v Q −1.17 (SE 0.06) v R −1.05 (SE 0.12) v H −0.64 (SE 0.11)
Statistically significant difference (p≤0.001) for the following comparisons: O v R & H; R v H

Relapse rates at 12 months among previous responders:
O 7.7% v R 9.0% (OR 1.07 [0.68–1.68] vs olanzapine) v Q 12.5% (OR 1.76 [0.66–4.74] vs olanzapine)
v H 30.0% (OR 6.57 [3.10–13.93] vs olanzapine)

Proportion of patients who had worsened at 12 months:
O 20.2% v R 24.8% (OR 1.29 [1.04–1.59] vs olanzapine) v Q 37.0% (OR 2.28 [1.47–3.54] vs olanzapine) v H 37.1% (OR 2.37 [1.60–3.52] vs olanzapine)
Weight gain, least squares mean: O 3.4kg (CI 2.9–4.0); p<0.001 v R; R 2.2kg (CI 1.5–3.0); Q 1.9kg (CI 0.5–3.3); H 2.2kg (CI 0.9–3.4)
Patients with weight gain >7% of baseline: O 760/1963 (39%) v R 153/549 (28%) v Q
20/80 (25%) v H 27/105 (26%)
Relapse months 3–12, based on subset of initial responders (total n=1682):
O 99/1292 (7.7%)
R 28/310 (9.0%); OR 1.07 (0.68–1.68) vs olanzapine
Q 5/40 (12.5%); OR 1.76 (0.66–4.74) vs olanzapine
H 12/40 (30.0%); OR 6.57 (3.10–13.93) vs olanzapine
p<0.001: O v H; R v H
Compliance (based on patient perception):
O 1637/1916 (85.4%) v R 445/547 (81.4%) v Q 61/84 (72.6%) v H 72/121 (59.5%)
p<0.001: O v H; R v H

Sexual dysfunction-related AE's during 12-month treatment period for olanzapine vs risperidone vs quetiapine vs haloperidol/odds ratio (95% CI) for comparison to olanzapine
Patient perception of sexual dysfunction: 55.7% vs 67.8% (OR 2.02, 95% CI 1.63, 2.49) vs 60.2% (OR 0.88, 95% CI 0.56, 1.39) vs 71.1% (OR 2.47, 95% CI 1.61, 3.77)
Loss of libido: 46.4% vs 60% (OR 2.05, 95% CI 1.67, 2.52) vs 54.6% (OR 1.16, 95% CI 0.72, 1.85) vs 68.1% (OR 3.25, 95% CI 2.14, 4.92)
Impotence/sexual dysfunction: 32% vs 46% (OR 2.17, 95% CI 1.72, 2.73) vs 43% (OR 1.26, 95% CI 0.74, 2.14) vs 52.3% (OR 3.04, 95% CI 1.94, 4.74)
Amenorrhea/menstrual disturbances: 29.5% vs 42.1% (OR 2.26, 95% CI 1.63, 3.15) vs 20.9% (OR 0.46; 95% CI 0.20, 1.05) vs 53.8% (OR 4.06, 95% CI 2.20, 7.51)
Dossenbach 2008 IC-SOHO study (36 month data)Dossenbach 2004Same as
Dossenbach 2004
36 monthsNRSame as Dossenbach 2004Schizophreniasame as Dossenbach 2004Same as
Dossenbach 2004
2293/NR/3835Olanzapine vs risperidone vs quetiapine
% responding to treatment at 36 months
78% vs 65% vs 47%
Median time to response (95% CI) mo: 5.2 (5.0 to 5.5) vs 6.3 (6.0 to 6.7) vs 11.3 (6.3 to 17.5)
Olanzapine as a reference
HR (95% CI): vs risperidone 0.8 (0.7 to 0.8), p<0.001, Number needed to treat (95% CI) at 36 mo 15 (10–31)
HR (95% CI): vs quetiapine 0.6 (0.4 to 0.7), p<0.001, nmber needed to treat (95% CI) at 36 mo 8 (4 to 50)

Risperidone as a reference
HR (95% CI): vs quetiapine 0.8 (0.6 to 1.0), p=0.037, Number needed to treat (95% CI) at 36 mo 12 (5 to −23)

% patients relapsed following treatment response: 12% vs 14% vs 18%
EPS
Olanzapine as reference
Adjusted OR (95% CI) vs Risperidone 5.63 (4.27 to 7.40), p<0.001, Number needed to treat (95% CI)at 36 mo 5 (5 to 7)
Adjusted OR (95% CI) vs Quetiapine 0.23 (0.07 to 0.75), p=0.015, Number needed to treat(95% CI at 36 mo −18 (−57 to −11)
Risperidone as a reference
Adjusted OR (95% CI) vs Qutiapine: 0.04 (0.01 to 0.13), p<0.001, Number needed to treat (95% CI) at 36 mo −4 (−5 to −4)

Tardive dyskinesia
Olanzapine as reference
Adjusted OR (95% CI) vs Risperidone: 4.15 (2.37 to 7.27), p<0.001, Number needed to treat at 36 mo 42 (26 to 105)
Adjusted OR (95% CI) vs Quetiapine : 1.37 (0.39 to 4.72), p=0.623, Number needed to treat at 36 mo 138 (30 to −53)
Risperidone as a reference
Adjusted OR (95% CI vs Quetiapine: 0.33 (0.09 to 1.16), p=0.084, Number needed to treat at 36 mo −59 (81 to −22)

Sexual dysfunction:
Olanzapine as a reference
Adjusted OR (95% CI) vs Risperidone 2.14 (1.70 to 2.70), p<0.001, Number needed to treat (95% CI ) at 36 mo 10 (7 to 22)
Adjusted OR (95% CI) vs Quetiapine 1.43 (0.78 to 2.60), p=0.246, Number needed to treat at 36 mo 39 (7 to −10)
Risperidone as a reference
Adjusted OR (95% CI) vs Quetiapine 0.67 (0.36 to 1.23), p=0.196, Number needed ot treat
at 36 mo −14 (17 to −5)

Weight gain>7% from baseline
Olanzapine as reference
Adjusted OR (95% CI) vs risperidone 0.63 (0.54 to 0.73), p<0.001, number needed to treat (95% CI) at 36 mo −9 (48 to −4)
Quetiapine as reference
Adjusted OR (95% CI) vs quetiapine 0.81 (0.55 to 1.21), p=3.00, number needed to treat at 36 mo (95% CI) −18 (12 to −5)
Etminan, 2003
Ontario
Database: Ontario Drug Benefit (ODB) claims databaseUnclearNRNROlanzapine
Quetiapine
Risperidone
SchizophreniaMean age=84.2
34.2% male
Race NR
NR
NR
3250
NR
NR
2984 (individual group n’s NR)
NRDiabetes
Diabetic events (% patients):
Olanzapine=2.1
Quetiapine=1.0
risperidone
2.1
Age - older adults
Feldman, 2004 United StatesAdvancePCS IncRetrospective6–9 monthsNRNRGeriatricMean age: 79.2 years 60.8% female
Ethnicity NR
NR/NR/1,836,799NR/NR/30,953Development of Diabetes Mellitus (Risk Ratio):
All combined conventional antipsychotics: 3.2; P<0.001
All combined atypicals: 3.3; P<0.001
clozapine: 5.8; P=0.002
olanzapine: 3.5; P<0.001
quetiapine: 2.5; P<0.001
risperidone: 3.4; P<0.001
NR
Fuller, 2003
Ohio
Database: Veteran’s Integrated Service Network 10Retrospective1/1/97 to 12/31/00NRRisperidone 2.8 mg
Olanzapine 10.0 mg
Fluphenazine 12.2 mg
Haloperidol 8.4 mg
Range of psychiatric diagnoses:
Schizophrenia=61%
Depression=47%
Bipolar Disorder=26%
Dementia=8%
Mean age=53
Gender NR
73% White
NR
NR
5837
NR
NR
5837
NRRisk (Hazard Ratio, 95% CI) of developing diabetes for olanzapine vs risperidone: Univariate analysis=HR 1.29, 95% CI 1.00 to 1.67; Multivariate analysis=HR 1.37, 95% CI 1.06 to 1.76
Ganguli, 2001
United States
Multiple sourcesRetrospective4 monthsNRNRSchizophreniaMean age: 41.3 years
56.5 Males
Caucasian: 57%
African-American:38%
Other: 5%
NR/NR/1000/0/100NRChange in Mean Body Weight/BMI at Endpoint:
Weight:
risperidone: 82.8kg, P=NS
olanzapine:
BMI:
risperidone:
olanzapine:
Garcia-Cabeza, 2003
Montes, 2003
Spain

Subjective Response Analysis from Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapine (EFESO)
Multicenter
Controlled
See aboveSee aboveNROverall mean dose:
Olanzapine: 13 mg/d
Risperidone: 5.4 mg/d
Haloperidol: 13.6 mg/d
Paranoid schizophrenia: 65.1%
Undifferentiated schizophrenia: 13.5%
Residual schizophrenia: 12.3%

Subjective response and compliance with antipsychotic treatment using 10 Item Drug Attitude Inventory (DAI-10)
Mean age: 35.4

63.9% male
Ethnicity NR
NR/2967/2657unclear;From Montes 2003:
Mean changes in scale scores for olanzapine vs risperidone vs conventional antipsychotics (p-value is NS unless otherwise specified and represents comparison to conventional antipsychotics group)
CGI-S: −1.8 vs −2.0 vs −1.5
GAF: 29.2 vs 32.2 vs 22.6
EuroQol-1:0.35 vs 0.36 vs 0.25
Visual Analogue Scale (0=worst state of health possible to 100=best state of health possible): 26
(p<0.05) vs 28 (p<0.05) vs 17.5
AWAD scale (subjective attitude towards medication; positive score=positive subjective response, negative score=negative response): 4.7 vs 3.1 vs 1.3
Subjective Response : Mean DAI-10 Score (range:10 to +10), baseline vs 6 months:
olanzapine: +0.17 vs +4.63
risperidone: +0.32 vs +3.42, p<0.001 vs Olz
haloperidol: −1.25 vs +1.68, p <0.001 vs Olz and p=0.003 vs Ris

Compliance with principal antipsychotic treatment, % of pts at each level data given as Olz vs Ris vs Hal
  High compliance: 84.8% vs 74.2% vs 69.8% (p=0.001 for Olz vs Ris)
  Moderate compliance: 11.1% vs 19.4% vs 27.1% (p=0.022 for Olz vs Hal)
  Low compliance: 2.5 % vs 5% vs 2.1%
  Nil: 1.6% vs 1.4% vs 1%

% of pts with EPS, baseline vs 6 month data, p=NR:
 Olz: 35.8% vs 31.9%
 Ris: 48.3% vs 44.6%
 Hal: 69.2% vs 66.3%
Gasquet, 2005
Europe (Denmark, France, Germany, Greece, Ireland, Italy, The Netherlands, Portugal, Spain and UK)
SOHO (secondary publication)
Prospectively collected, multicenter study dataProspective6 mo (interim analysis of planned 3-yr term)NROlanzapine 11.1 mg/day (SD 5.0)
Risperidone 4.6 mg/day (SD 2.6)
Previously untreated schizophrenicsMean age 33.6 yrs
60% male
Ethnicity NR
1033/NR/919134/NR/919EQ-5D VAS at 6 months: O 64.4 (SD 18.1) v R 61.1 (SD 18.8); adjusted mean difference O v R: −3.73 (CI −1.48 to −5.97); p=0.001Weight gain at 6 months: O 3.1kg (SD 4.9) v R 2.1 (SD 4.6); adjusted mean difference O v
R: −1.0 (CI −1.8 v −0.1)
Gianfrancesco, 2006a
United States
Database: PharMetricsRetrospectiveJanuary 1999 through August
2003
NRAtypical Antipsychotics
Risperidone: 3.0mg/day
Olanzapine: 11.4mg/day
Quetiapine: 264mg/day
Ziprasidone: 86mg/day
Typical Antipsychotics
Haloperidol: 10.5mg/day
Perphenazine: 13.5mg/day
Thioridazine: 128mg/day
Thiothixene: 11.2mg/day
Schizophrenia or schizoaffective disorderMean age (years): 41.5
% male: 48.9
NR/NR/5683NR/NR/5683Comparisons of treatment duration
Treatment duration for risperidone, olanzapine, and ziprasidone were not significantly different from the typical antipsychotics, but quetiapine demonstrated a nonsignificant trend for shorter treatment durations compared with the combined group of typical agents (P=0.091). Quetiapine had significantly shorter treatment durations than risperidone (P=0.024) and olanzapine (P=0.004). Differences between other atypical agents were not significant.
Patient characteristics with significant increasing associations with treatment duration included age, switch from another antipsychotic, substance dependence/abuse, more versus less managed form of coverage, and earlier date for start of treatment episode (all P<0.05).
NR
Gianfrancesco, 2006b
United States
Medical and prescription claims data for commercially insured patientsRetrospective1999 to August 2003UnclearRisperidone, olanzapine, quetiapine, ziprasidone mean dosages NRSchizophreniaMean age=42
43% male
Ethnicity NR
NR/NR/3807NR/NR/3807Hazard ratios (95% CI) for risk of hospitalization
Olanzapine vs risperidone=1.34 (1.03, 1.74)
Risperidone vs quetiapine=1.05 (0.71, 1.55)
Risperidone vs ziprasidone=1.14 (0.55, 2.37)
Olanzapine vs quetiapine=1.40 (0.94, 2.07)
Olanzapine vs ziprasidone=1.52 (0.73, 3.15)
Ziprasidone vs quetiapine=0.92 (0.42, 2.02)
NR
Gianfrancesco, 2002
United States
Database: Two mixed indemnity and managed care health plans located in the northeastern and southeastern United States (unspecified)RetrospectiveJanuary 1996 through December 1997Risperidone=6.8 months
Olanzapine=6.1 months
High-potency conventionals=7 months
Low-potency conventionals=7.1 months
Clozapine=9.4 months
Mean dosages in form of risperidone equivalents:
Risperidone=2.3 mg
Olanzapine=3.6 mg
High-potency conventionals=1.7 mg
Low-potency conventionals=1.7 mg
Clozapine=2.5 mg
Psychosis diagnosis (schizophrenia, bipolar and manic, major depressive, dementia, other psychoses)Untreated vs treated (restricted to those WITHOUT
Type 2 Diabetes at 4 months prior to observation)
Mean age=41.9 vs 45.3
% male=40.4% vs 36.6%
Race nr
NR
NR
NR
NR
NR
NR
NROdds Ratio (vs Risperidone) for 12 months of treatment (extrapolated from 1-month treatment rates) (excluded patients with pre-existing Type II Diabetes identified at 8-month screening):
Olanzapine=3.53, p<0.05
Clozapine=8.45, p<0.05

Frequency of Type 2 Diabetes after at least 12 months' treatment (excluding patients with pre-existing Type II Diabetes identified at 8-month screening):
Risperidone=2/90 (2.2%)
Olanzapine=4/56 (7.1%)
Clozapine=1/4 (25%)
Gianfrancesco, 2003a
United States
Database: Blue Cross/Blue Shield claims databaseRetrospectiveApril 1997 through October 2000Risperidone=9.1 months
Olanzapine=8.7 months
Quetiapine=7.1 months
Conventionals=12.1 months
Risperidone
Olanzapine
Quetiapine
Conventionals

Mean doses NR
Schizophrenia=14%
Bipolar and manic=35%, Major depressive=38%, Other psychoses=13%
Mean age=37.5
41% male
Race NR
NR
NR
6582 patients
Treatment episodes: Risperidone=2860, Olanzapine=2703, Quetiapine=922, Conventional antipsychotics=2756
NR
NR
Analyzed=6582 patients (Treatment episodes: Risperidone=2860, Olanzapine=2703, Quetiapine=922, Conventional antipsychotics=2756)
NRFrequency of Type II Diabetes at 4–8 months/8–12 months/>12 months:
Risperidone=0.2/0.0/0.6
Olanzapine=0.2/1.3/3.0
Quetiapine=0.5/1.2/0.9
Conventional=0.0/1.9/1.4

One-month odds ratios (95% CI) converted to 12-months for each drug vs no
antipsychotic treatment:
Risperidone=0.660 (0.311 to 1.408)
Olanzapine=1.426 (1.046 to 1.955)
Quetiapine=0.976 (0.422–2.271)
Conventionals=1.049 (0.688–1.613)
Gianfrancesco, 2003b
United States
Database: Two mixed indemnity and managed care health plans located in the northeastern and southeastern United States (unspecified)RetrospectiveJanuary 1996 through December 1997Patients not taking antipsychotics=13.7 months
Risperidone=6.1 months
Olanzapine=5.4 months
High-potency Conventional Antipsychotics=6.5 months
Low-potency conventional antipsychotics=6.5 months
(Risperidone equivalents)
Risperidone 2.1 mg
Olanzapine 3.4 mg
High-potency conventional antipsychotics 1.6 mg
Low-potency conventional antipsychotics 1.6 mg
% patients NOT taking antipsychotics/%
patients TAKING antipsychotics:
Bipolar=48.1%/30.6%
Major Depressive Disorder=39.7%/664.5%
Manic=12.2%/4.9%
Patients NOT taking antipsychotics/Patients TAKING antipsychotics:
Mean age=41.8/42.2
% male=38.9%/31.8%
Race NR
NR
NR
5723
NR
5236 patients (Patients NOT taking antipsychotics=264 4; Risperidone=849, Olanzapine=656, High-potency conventional antipsychotics=785, Low-potency antipsychotics=302) (excludes those found to have pre- existing Type II diabetes at the 4- month screening period)
NR12-month odds ratios (converted from 1-month estimates) that excludes patients found to have pre-existing Type II diabetes at 8-month screening:
Relative to Untreated
Risperidone=1.024 (0.351–3.015)
Olanzapine=4.289 (2.102–8.827)

Olanzapine vs risperidone-4.189, p=0.02958
Gibson, 2004
United States
Database: Michigan Medicaid administrative claims data set from Michigan's Department of Community Health (MDCH)RetrospectiveJanuary 1996 through September 19971 yearMean initial dosages:
olanzapine 9.9mg
risperidone 3.8mg
haloperidol 18.2mg
SchizophreniaHaloperidol/Risperidone/Olanzapine:
Mean age=39.7/40.5/40.7 years
Women (%)=53/48/53
Ethnicity=NR
3,642/1191/1191NR/NR/1191Patterns of use changes:
individuals increased usage of olanzapine as their only antipsychotic medication from 41% to 46%
individuals decreased usage of risperidone as their only antipsychotic medication from 61% to 42%
individuals decreased usage of haloperidol as their only antipsychotic medication from 81% to 39%
Cost reduction: Olanzapine was associated with $2552 lower total cost than risperidone and $2323 lower costs than haloperidol
NR
Gomez, 2000
Spain

Estudio Farmacoepidemiologico en esquizofrenia con Olanzapine (EFESO)
Multicenter ControlledSchizophrenia patients were included when a change of medication was indicated or a new antipsychotic drug treatment was being initiated for whatever reason. Choice of new drug was made by the treating physician.6 monthsOlanzapine 13.01 mg
Risperidone 5.39 mg
Haloperidol 13.64 mg
NRDeath
Weight gain
Mean age=35.4
63.6% male
Race NR
NR
NR
2949
798 (25.7%)
withdrawals
506 (17.1%) lost to fu
2949 analyzed
NRDeath
Olanzapine: 3 (0.1%)
Control group: 1 (0.1%)

Suicide
Olanzapine: 1 (0.05%)
Control group: 1 (0.1%)

Weight gain
Olanzapine: 146 (6.9%)
Risperidone: 8 (1.9%)
Haloperidol: 1 (0.9%)
Olanzapine vs. risperidone: p<0.001
Olanzapine vs. haloperidol: p=NS
Gupta, 2004
United States
Olean General Hospital at the SUNY Upstate Medical University at SyracuseProspectiveNR10 weeksQuetiapine 4 weeks
392.5 mg/day
Schizophrenia, schizoaffective disorder, bipolar disorder, psychotic disorder, or major depression with psychotic features.Mean age =46.6 years
56% male
Ethnicity: NR
NR/NR/162/2/NRPositive and Negative Syndrome Scale (PANSS): NS
Simpson-Angus-Scale (SAS): NS
Mean weight loss=2.25kg, p=0.03
BMI declined to 34.4kg/m2, p=0.065
fasting glucose, lipid profile, hemoglobin A1c, serum triglycerides: NS
Patients switched from olanzapine to quetiapine
Haro, 2006
SOHO (secondary publication)
3-year effectiveness

Europe
Same as Haro 2005Same as Haro 2005NR3 yearsSame as Haro 2005Same as Haro 2005; only patients with none or 1 missing visitMean age 39.8 years
56.7% male
Ethnicity NR
9857
8072
7728
nr/nr/7728Patients maintaining treatment for 36 months Olanzapine 1851, Risperidone 619, Quetiapine 126, Amisulpride 85, Clozapine 123, Oral typical NR
Depot typical NR
Patient discontinuing for any reason (%) Olanzapine 36.4, Risperidone 42.7, Quetiapine 66.1, Amisulpride 50.4, Clozapine 33.8, Oral typical 53.1
Depot typical 50.2
Patient discontinuing for lack of efficacy (%) Olanzapine 18.4, Risperidone 22.7, Quetiapine 48.3, Amisulpride 28.7, Clozapine 17.8, Oral typical 33.8, Depot typical 31.4
Patient discontinuing for intolerability(%) Olanzapine 6.4, Risperidone 10.1, Quetiapine 14.2, Amisulpride 13.7, Clozapine 7.2, Oral typical 13.3, Depot typical 9.2
Hospitalization for exacerbation of schizophrenia
Hazard ratio (95% CI) Olanzapine 1 Risperidone 1.04 (0.88, 1.23) Quetiapine 1.64 (1.31, 2.05) *** Amisulpride 1.39 (1.01, 1.92) * Clozapine 1.13 (0.83, 1.53) Oral typicals 1.39 (1.08, 1.79) ** Depot typicals 1.44 (1.10, 1.88) **
Suicide attempt % Olanzapine 2.1, Risperidone 1.9, Quetiapine 1.4, Amisulpride 3.1, Clozapine, Oral typical 0.4, Depot typical 3.5
EPS % Olanzapine 14.7, Risperidone 32.2, Quetiapine 13.4, Amisulpride 16.8, Clozapine 17.2, Oral typical 31.4, Depot typical 42.8
Tardive dyskinesia % Olanzapine 5.9, Risperidone7.8, Quetiapine 6.0, Amisulpride 9.8, Clozapine 6.2, Oral typical 8.7, Depot typical 12.9
Loss of libido/impotence Olanzapine 46.9, Risperidone 52.2, Quetiapine 39.8, Amisulpride 49.2, Clozapine 48.5, Oral typical 50.7, Depot typical 49.7
Gynecomastia, galactorrhea, amenorrhea Olanzapine 11.5, Risperidone 16.7, Quetiapine 12.4, Amisulpride 18.0, Clozapine 16.4, Oral typical 14.9, Depot typical 13.8
Mean (SD) weight change (kg) Olanzapine 3.6(8.9), Risperidone 2.5(8.5), Quetiapine 0.6(7.9), Amisulpride 0.5(10.8), Clozapine 3.0(11.5), Oral typical 1.5(6.3), Depot typical 2.6(10.3)

* p ≤ 0.05.
** p ≤ 0.01.
*** p ≤ 0.001.
Haro, 2006
SOHO (secondary publication)
12-month medication maintenance outcomes

Europe
Same as Haro 2005Same as Haro 2005NR12 monthsSame as Haro 2005Same as Haro 2005Mean age 40 years
56.9% male
Ethnicity NR
8519/NR/7186NR/NR/7186Medication maintenance at 12 months (% pts):
Highest frequencies: Clozapine=79.5% and Olanzapine=77%
Lowest frequencies: Quetiapine=51.4% and amisulpride=58.2%
Frequencies for other cohorts NR

Odds ratios (95% CI) of associated with maintenance compared to olanzapine:
Risperidone: 0.72 (0.62, 0.83)
Quetiapine: 0.36 (0.29, 0.44)
Amisulpride: 0.53 (0.39, 0.71)
Clozapine: 1.65 (1.20, 2.28)
Oral typical: 0.56 (0.45, 0.70)
Depot typical: 0.58 (0.46, 0.75)
NR
Haro, 2006
SOHO (secondary publication)
3-year remission/relapse outcomes

Europe
Same as Haro 2005Same as Haro 2005NR3 yearsSame as Haro 2005Same as Haro 2005; only patients with none or 1 missing visitMean age 40.2 years
57.6% male
Ethnicity NR
10,218/7112/6516NR/NR/6516Remission=Scores of 3 or below on the CGI overall severity, positive symptoms score, negative symptoms score, AND cognitive symptoms score

Odds ratios (95% CI) of remission compared to olanzapine:
Amisulpride: 0.72 (0.56, 0.94)
Clozapine: 0.78 (0.65, 0.95)
Depot typical: 0.59 (0.50, 0.69)
Oral typical: 0.64 (0.55, 0.74)
Quetiapine: 0.65 (0.56, 0.76)
Risperidone: 0.74 (0.66, 0.83)

Odds ratios (95% CI) of relapse compared to olanzapine:
Amisulpride: 1.37 (0.99, 1.90)
Clozapine: 1.09 (0.78, 1.53)
Depot typical: 1.69 (1.31, 2.18)
Oral typical: 1.65 (1.32, 2.08)
Quetiapine: 2.15 (1.71, 2.69)
Risperidone: 1.30 (1.09, 1.54)
NR
Haro, 2005
Europe
SOHO (primary publication)
Prospectively collected, multicenter study dataProspective6 mo (interim analysis of planned 3-yr term)NROlanzapine 12.1 mg/day (SD 5.9)
Risperidone 4.9 mg/day (SD 2.8)
Quetiapine 391 mg/day (SD 216)
Clozapine 238 mg/day (SD 140)
SchizophreniaMean age 40 yrs
59.4% male
Ethnicity NR
NR/NR/109721944/NR/9028 (at 6 months)Outcomes at 6 months-
EQ-5D VAS rating (mean):
O 63.2 (SD 19.5)
R 61.2 (SD 18.8); OR −2.3 (−3.4 to −1.2) vs olanzapine; p<0.0001
Q 59.9 (SD 19.9); OR −3.0 (−4.5 to −1.4) vs olanzapine; p<0.0001
C 61.0 (SD 20.3); OR 0.5 (−1.7 to 2.6) vs olanzapine
Socially active:
O 3990/4716 (84.6%)
R 1410/1711 (82.4%); OR 1.27 (1.05 to 1.54) vs olanzapine; p<0.05
Q 544/690 (78.9%); OR 1.67 (1.29 to 2.16) vs olanzapine; p<0.001
C 246/301 (81.6%); OR 1.25 (0.87 to 1.80) vs olanzapine
Relationship with spouse or partner:
O 1467/4716 (31.1%)
R 532/1711 (31.1%); OR 1.06 (0.81 to 1.39) vs olanzapine
Q 206/690 (29.9%); OR 1.06 (0.72 to 1.57) vs olanzapine
C 61/301 (20.3%); OR 1.23 (0.72 to 2.09) vs olanzapine
Paid employment:
O 1080/4716 (22.9%)
R 370/1711 (21.6); OR 1.15 (0.88 to 1.51) vs olanzapine
Q 206/690 (29.9%); OR 1.21 (0.81 to 1.81) vs olanzapine
C 61/301 (20.3%); OR 1.66 (0.99 to 2.78) vs olanzapine
Suicide attempt since baseline visit:
O 75/4716 (1.6%)
R 41/1711 (2.4%); OR 0.77 (0.47 to 1.25) vs olanzapine
Q 10/690 (1.4%); OR 1.17 (0.52 to 2.66) vs olanzapine
C 4/301 (1.4%); OR 0.92 (0.32 to 2.66) vs olanzapine
NROnly data abstracted for olanzapine, risperidone, quetiapine, clozapine arms
Haro, 2009 SOHO (secondary publication) 36-month data from treatment discontinuation
Alonso 2009 SOHO(secondary publication)HRQOL data
Novick 2009 SOHO (secondary publication) Recovery data in the outpatient setting
Novick 2009 SOHO (Tolerability of outpatient antipsychotic treatment..”
Usall 2007 SOHO
Same as Haro 2005Same as Haro 200536 months analysisNRMean endpoint doses
olanzapine: 11.8 mg/day
risperidone:4.5 mg/day
quetiapine: 320mg/day
SchizophreniaMean age: 34y
59% male
Ethnicity: NR
NR/NR/1009NR/236*/931
* lost to Follow-up before changing medication
% of patients discontinuing treatment by 36 mo
Olanzapine vs Risperidone vs typicals versus other atypicals
28.9% vs 36.2% vs 44.5% vs 34.7%

Cox proportional HR for discontinuation of treatment by 36 months-
Higher than olanzapine for Risperidone and typical
Typicals: HR 1.76; 95% CI 1.11–2.78
Risperidone: HR 1.36 95% CI 1.02–1.82
HR for atypicals similar to olanzapine:
Atypicals: HR 1.43 (95% CI, 0.85–2.40)

Patients with higher CGI-score at baseline had higher risk of discontinuing treatment at 36 months
HR 1.18, 95% CI 1.06–1.30
EuroQOL-5D mean (SD) score at 36 mo: 0.80 (0.25)
Factors associated with achieving long lasting symptomatic remission vs functional remission vs adequate QOL during 3 year follow-up
OR with respect to Olanzapine
Risperidone (OR): 0.785, p= 0.0062 vs 0.795 (p=0.795) vs 0.639 (p<0.0001)
Quetiapine (OR)0.456 (p<0.0001) vs 0.760 (p=0.2121) vs 0.443 (p<0.0001)
Clozapine (OR) 0.944 (p=7514) vs 0.555 (p0.0881) vs 1.101 (p=0.6098)

Response overall CGI: OR for gender (female reference category) 95% CI, p-Value
Olanzapine cohort 0.88 (0.78 to 1.00), p=0.040
Risperidone cohort 0.90 (0.74 to 1.10), p=0.2969
Clozapine 0.56 (0.34 to 0.93) p=0.252, p=0.0252
EQ-VAS change from baseline
Difference in rating by gender (female reference category), 95% CI, p-value
Olanzapine cohort: −1.52 (−2.53 to −0.50), p=0.0033
Risperidone cohort: 0.27 (−1.28 to 1.83), p=0.7300
Clozapine cohort: −2.03 (−6.06 to 2.00), p=0.3243
% of patients with adverse events
Olanzapine vs risperidone vs other typicals versus typicals
EPS: 3.6% vs 17.1% vs 9.9% vs 13.7%
TD: 0.4% vs 1.1% vs 1.7% vs 1.2% loss of libido/impotence: 25.5% vs 38.9% vs 37.9% vs 41.3%
Prolactin-related: 3.8% vs 9.2% vs 10% vs 3.1%
7% weight gain: 30.8% vs 23.2% vs 22.7% vs 10.7%

Tolerability (Novick 2009)Olanzapine vs risperidone vs quetiapine vs clozapine EPS

% of patients with EPS at 36 mo 9.4% vs 15.6% vs 11.9% vs 12.9%
OR (95% CI) in comparison to olanzapine
Risperidone: 2.55 (2.16 to 3.02), Quetiapine 1.36 (1.02 to 1.81), Clozapine 1.19 (0.81 to 1.74)
Tardive dyskinesia
% of patients with tardive dyskinesia at 36 mo: 3.4% vs 4.8% vs 5.3% vs 7.1%
OR (95 % CI) in comparison to olanzapine
Risperidone: 2.47 (1.56 to 3.94), Quetiapine 1.77 (0.89 to 3.51) Clozapine 2.37 (0.96 to 5.85)
Loss of libido/impotence
% of patients with loss of libido/impotence at 36 mo
32.5% vs 36.5% vs 34.2% vs 40.9
OR (95% CI) in comparison to olanzapine
Risperidone 1.38 (1.20 to 1.60), quetiapine 1.07 (0.86 to 1.33) vs 1.39 (1.04 to 1.86)

mean (SD) Weight change from baseline to 36 mo: 4.2 (8.7) vs 2.7 (7.6) vs 1.7 (8.4) vs 2.6 (9.5)
% of patients with >7% weight gain at 36 mo from baseline: 40.6% vs 33.7% vs 30.9% vs 29.5%
Haro, 2008
10 European countries
Data from the SOHO (Schizophrenia Health Outcomes) studyProspective observational study3 year follow-up3 yearsOlanzapine Is the reference medication
Other medications include risperidoen, quetipine, amisulpride, clozapine, depot typicals
Patients at least 18 years of age with initiating or changing antipsychotic medication for the treatment of schizophrenia; presenting within the normal course of care in the outpatient setting or in the hospital when admission was planned for the initiation or change of antipsychotic medication and discharge planned within 2 weeks

5950 patients analyzed
Mean duration of illness: 11.9 years
9% never treated for schizophrenia
Concomitant medication: 19% on
anticholinergics; 18% on antidepressants;
9% on mood stabilizers; 37% on anxiolytics
CGI overall (SD): 4.4 (1.0)
Mean age: 40.3 years
Male: 58%
Ethnicity: NR
NR/NR/5950NR/NR/5950Remission was defined as a score of 3 (mild severity) or less on the CGI overall severity score, the CGI positive symptoms score, the CGI negative symptoms score and the CGI cognitive symptoms score that was maintained for a period of six months or more

2301 (38.7%) never achieved remission during the 3-year follow-up (prolonged course), 933 (15.7%) achieved remission but relapsed (remission and relapse) and 2716 (45.7%) achieved and maintained remission (persistent remission).

"Patients prescribed risperidone, quetiapine or depot typicals at the baseline visit had a lower chance of achieving remission compared with those prescribed olanzapine"

Relationship between independent variables (age of onset, years since onset, male, never treated before baseline, has a spouse/partner, paid employment, socially active, CGI overall, CGI positive, CGI negative, CGI cognitive, hostile behaviours, BMI, anxiolytics, and ood stabilizers) given in table. "Females, patients with better social functioning at baseline (living independently, in paid employment, socially active or having a spouse or partner) and with a shorter duration of illness had a more favourable course"
NR
Haukka 2008
Finland
National Hospital Discharge Register, Statistics Finland, and a nationwide prescription register.RetrospectiveJanuary 1, 1997-December 31, 2003Not reportedclozapine
olanzapine
typical antipsychotics (haloperidol zuclopenthixol, other or mixed)
antidepressants (fluoxetine, citalopram, paroxetine, sertraline, mianserin, other or mixed)
All individuals in Finland who (a) had been hospitalized with a diagnosis of attempted suicide, (b) had at least one hospitalization registered in the National Hospital
Discharge Register with a schizophrenia diagnosis and (c) were at least 16 years of age when the index hospitalization began.
Median age 35.63 (males), 41.05 (females)
51% male
Race not reported
NR
NR
1,611
NR
NR
1,611
Propensity-score adjusted hazard ratios (95% CI) vs no antipsychotic use
Suicide attempts
Clozapine: 0.74 (0.35, 1.57)
Olanzapine: 1.37 (0.87, 2.14)
Haloperidol: 0.92 (0.46, 1.83)
Perphenazine: 1.73 (0.89, 3.34)
Other or mixed: 1.34 (1.10, 1.62)
Suicides
Clozapine: 0.67 (0.16, 2.85)
Olanzapine: 0.40 (0.11, 1.44)
Haloperidol: 1.03 (0.18, 5.98)
Perphenazine: 0.27 (0.01, 4.73)
Other or mixed: 0.62 (0.39, 0.98)
All-cause mortality
Clozapine: 0.57 (0.19, 1.71)
Olanzapine: 0.31 (0.12, 0.79)
Haloperidol: 0.50 (0.15, 1.65)
Perphenazine: 0.20 (0.04, 1.06)
Other or mixed: 0.54 (0.40, 0.74)
NA
Hayhurst, 2002
UK
South Manchester University Hospitals NHS TrustRetrospective cohort

Controlled
NR2 yearsClozapine 425 mg/day other antipsychotics: not specifiedSchizophreniaMean age: 42.5 y
65.1% male
Ethnicity: NR
NR/NR/126NR/NR/126Reduction in mean number of admissions between 2y before clozapine and 2y after, clozapine vs. other:
 −0.54 vs + 0.25. p <0.01
Reduction in mean length (days) of stay between 2y before cloz. and 2 y after, clozapine vs. other:
 −33.37 vs −1.35d, p<0.05
% of clozapine users who came off clozapine in 2 years after starting: 44.4%
mean reduction in bed-days over 2 yr follow-up period for cloz. users: −33 bed days
NR
Hedenmalm, 2002
International
WHO databaseRetrospectiveMedian treatment duration: R: 13 days, C: 52 days, O: 115 daysNRRisperidone
Clozapine
Olanzapine
SchizophreniaNR
NR
NR
NR/NR/8680/0/868NR74% of cases of discontinuation, glucose tolerance improved after discontinuation. After rechallenge (N=24), following resulted in recurrence of glucose intolerance: clozapine: 18, olanzapine: 5, risperidone: 1
Hennessy, 2002
United States
3 US Medicaid programmesRetrospectiveNRNRQuarter 1, Quarter 2, Quarter 3, Quarter 4
clozapine: <243, 243–385, 386–543, >543
risperidone: <2.8, 2.8–5.0, 5.1–6.5, >6.5
haloperidol: <3.5, 3.5–7.5, 7.6–15.0, >15.0
thioridazine: <51, 51–102, 103–204, >204
Schizophrenia, control group of patients with psoriasis71.5% over 34 yrs of age
54% Female
Ethnicity NR
NR/NR/NRNR/NR/NRAdjusted rate ratios; 95% Cis
Patients with glaucoma: cardiac arrest/ventricular arrhythmia; death:
clozapine: 1.7 (1.0–2.9); 3.4 (2.1–5.5)
haloperidol: 2.2 (1.7–3.0); 4.5 (3.6–5.7)
risperidone: 3.1 (2.2–4.5); 5.8 (4.3–8.0)
thioridazine: 2.2 (1.6–3.); 4.0 (3.1–5.2)
Patients with psoriasis: cardiac arrest/ventricular arrhythmia; death:
clozapine: 1.9 (1.0–3.7); 2.6 (1.5–4.5)
haloperidol: 2.4 (1.5–3.9); 3.2 (2.2–4.8)
risperidone: 3.2 (1.9–5.4); 4.1 (2.7–6.4)
thioridazine: 2.4 (1.4–3.9); 2.9 (2.0–4.4)
Those with treated schizophrenia has higher rates of cardiac arrest and ventricular arrhythmia over those non-treated: ratio: 1.7–3.2
Herceg, 2008Vrapce Psychiatric Hospital, Zagreb, CroatiaRetrospectiveJan 1, 2003–Dec 31, 20042 yrsRisperidone vs olanzapine vs clozapine
Newly diagnosed schizophrenia
Mg/day, median, Interquartile (IQ) range 4 (4–6) vs 10 (10–15) vs 250 (200–300)
Chronic schizophrenia
Mg/Day, median, IQ range: 4(3–6) vs 15 (10.0–17.5) vs 200 (150–300)
Newly diagnosed schizophrenia and Chronic schizophreniarisperidone vs olanzapine vs clozapine
Newly diagnosed schizophrenia
Age median, (IQ range): 24 (20–32) vs 27 (22–39) vs 33 (27–46)
% male: 64.0% vs 44.0% vs 77.0%
Chronic Schizophrenia
Age, median (IQ range):38 (30–35) vs 36 (28.5–44.0) vs 40 (33.5–47.5)
% male: 64.0% vs 53.0% vs 60.0%)
Ethnicity: NR
NR/831/533298/NR/533Newly diagnosed schizophrenia
risperidone vs olanzapine vs clozapine
% rehospitalized taking atypical antipsychotics:17.3% vs 19.2% vs 11.5, p=NS
Time to first rehospitalization at 2 years: longest for olanzapine (difference with other groups, NS)
chronic schizophrenia
% rehospitalized taking atypical antipsychotics by the 2nd year follow-up: 13% vs 12% vs 14%, p=NS
Time to first rehospitalization: longest for risperidone (Difference with other groups, NS)
NR
Ho, 1999
United States
Mental Health Clinical Research Center, University of IowaRetrospective4 weeks6 monthsRisperidone 6.0 mg/day (N=21)
Olanzapine 13.7 mg/day (N=21)
SchizophreniaMean age: 31.5 years
76.2% male
Ethnicity NR
NR/NR/42NR/NR/26olanzapine vs risperidone, change from baseline, p value
At discharge
Symptom score:
 negative symptom dimension: −2.8(0.76)* vs −1.8(0.61)*, p=0.49
 psychotic symptom dimension: −1.3(0.55)* vs −1.9(0.53)*, p=0.82
 disorganized symptom dimension: −1.8(0.68)* vs −2.1(0.77)*, p=0.68
 Total SANS/SAPS: −5.8(1.58)* vs −5.9(1.46)*, p=0.69
 Total BPRS: −9.0(2.91)* vs −6.5(2.47)*, p=0.14
GAS score: 8.9(2.18)* vs 6.2(1.4)*, p=0.09
(*p<0.05 vs baseline, within group comparison)

At follow-up
Symptom score:
 negative symptom dimension: −1.5(0.94) vs −1.5(1.18), p=0.84
 psychotic symptom dimension: −1.4(0.5)* vs −3.9(0.64)*, p=0.03
 disorganized symptom dimension: −0.8(0.7) vs −3.2(1.1)*, p=0.36
 Total SANS/SAPS: −3.7(1.23)* vs −8.6(2.39)*, p=0.3
GAS score: 8.8(4.01)* vs 13.9(2.43)*, p=0.52
Quality of life scores:
 occupational impairment: −0.5(0.43) vs 0.5(0.27), p=0.06
 financial dependence: 0.7(0.27) vs 0.7(0.26), p=0.49
 impairment in performance of household duties: −0.7(0.24)* vs −0.6(0.4), p=0.91
 relationship impairment with family member: −0.01(0.27) vs −0.4(0.2), p=0.27
 relationship impairment with friends: −0.4(0.29) vs −0.2(0.25), p=0.37
 enjoyment of recreational activities: −0.8(0.36) vs −0.3(0.38), p=0.77
 satisfaction: −0.5(0.22) vs −0.8(0.30), p=0.67
 overall psychosocial functioning: −0.7(0.31) vs −1.15(0.22)*, p=0.24 (*p<0.05 vs baseline, within group comparison)
EPS at discharge:
 SAS: 0(0.19), 0.4(0.56), p=0.31
 BAS: −0.1(0.15) vs 0.6(0.20)*, p=0.001 (*p<0.05 vs baseline, within group comparison)
Hodgson, 2005
England
Case Notes: 26 consultant psychiatristsRetrospective1994 to 2001NRClozapine=332.3mg/day
Olanzapine=12.1mg/day
Risperidone=4.7mg/day
Schizophrenia or schizoaffective disorderClozapine/Olanzapine/Risperidone
Mean age (years)=37.3/41.8/39.4
% male=82/60/65
550/261/253NR/NR/253Patients treated with risperidone and clozapine were 1.3 and 0.56 times, respectively, more likely to discontinue compared to olanzapine
Median time to discontinuation
Risperidone=274 days
Olanzapine=522 days
Clozapine=6 years
One serious adverse event was reported: intussusception in a patient taking clozapine. Side effects were not a common primary reason for medication discontinuation and therefore were not reported by the authors.
Hrdlicka, 2009patients receiving routine clinical care at the department of child psychiatryRetrospective1997–20076 weeksRisperidone vs olanzapine vs ziprasidone vs clozapine
Mean dose (SD) at week 6: 2.7 mg(1.3) vs 15.0mg (6.1) vs 80.0 mg(0.0) vs 247.5 mg(118.0)
Schizophrenia, schizoaffective disorder and other schizophrenic disordersMean age, yrs (SD)15.8 (1.6) range (10.5–18.8) yrs
% male: 47.7%
NR/109/10952/NR/109Risperidone vs olanzapine vs clozapine
mean change in weight between baseline and week 6 (Kg): +3.6 (2.6) vs +4.4 (2.5) vs + 2.1 (4.0), p=0.286
NRWeight gain data from ziprasidone not available at week 6 for statistical analysis because of early discharges and drop outs
Jerrell, 2007
United States
Medical and pharmacy claims informationRetrospectiveJuly 1, 2002 to June 30, 2004NRAtypical antipsychotics:
Aripiprazole
Ziprasidone
Quetiapine
Risperidone
Olanzapine
Clozapine
Typical antipsychotics:
Haloperidol
Fluphenazine
Primary or secondary diagnosis of schizophrenia51% of sample was ≥40 years of age
51% male
62% African American
NR/NR/2231NR/NR/2231Health Outcomes
For cerebrovascular conditions, there were no significant differences between groups
For heart disease conditions, aripiprazole had a lower estimate for myocardial infarctions and ischemic heart disease compared to both typical antipsychotics (P=0.006), risperidone had a lower incidence rate for arrhythmias compared to both typical antipsychotics (P=0.007).
The incidence rate for cardiomyopathy was significantly lower for aripiprazole than for both typical antipsychotics (P=0.02).
The incidence of being diagnosed with incident hypertension was significantly higher for those taking ziprasidone compared to both typical antipsychotics (P=0.01)
See outcomes column
Joyce, 2005
United States
Medical and pharmaceutical claims from the PharMetrics Patient-Centric DatabaseRetrospectiveMarch 1, 2001 and August 31, 2003≥12 monthsRisperidone: between 0.5mg and 8mg daily
Olanzapine: between 2.5mg and 40mg daily
Quetiapine: between 100mg and 800mg daily
Ziprasidone: between 40mg and 160mg daily
Schizophrenia or Schizoaffective disordersZiprasidone/Risperidone/Olanzapine
Mean age (years): 40.1/43.4/45.3
% male: 36.9/42/44.9
NR/NR/1810NR/NR/1810Compliance and Persistence
Compliance was significantly higher among those prescribed ziprasidone compared with the other treatment groups (P<0.01)
Persistence in the first year was 30 days longer among those prescribed ziprasidone compared with the other treatment groups, though not significant (persistence in days: ziprasidone=228; risperidone=193; and olanzapine=201)
Health Care Costs
Ziprasidone treatment group had the highest total annual cost compared to the other two treatment groups. Though change in cost from pre- to post index periods was not significantly different among the treatment groups. Psychiatric-related costs decreased significantly more for the ziprasidone treatment group than the other two groups (risperidone, P=0.0116 and olanzapine, P=0.0021)
NR
Kane, 1993
United States
NRProspective≥ 1 yearNRClozapine
CAPD
Schizophrenia/schizoaffectiveMean age=26.8
62.8% male
Race NR
NR
NR
437 (Clozapine=28, CAPD=409)
NR
NR
437
NRTardive dyskinesia
Clozapine=2 cases
CAPD=NR
Kasper, 2001
9 countries in Europe and Australasia
Riverview Hospital, British ColumbiaRetrospective4 monthsNRRisperidone (N=30) : 4.89 mg/day vs. olanzapine (N=30): 17.19 mg/dayAged 18–60, schizophrenia-types: paranoid, schizoaffective--disorder, Bipolar affective disorder, undifferentiatedMean Age: 35.7 years
Male: 62%
Ethnicity: NR
NR/NR/60NR/NR/37Percentage of Patients Discharged on Original Therapy:
R: 40% vs O: 13.3%; P<0.05
Treatment success: R: 40% vs O: 27%; P<0.01
Switched due to lack of efficacy: R: 37% vs O: 57%; P=NS
Switched due to side effects: R: 10% vs O: 63%; P<0.05
Treatment-emergent side effects:
Total # of patients with side effects: R: 43.3% vs O: 40%
EPS symptoms: 6/30 (20%)
Akathisia: R: 5 vs O: 1
Stiffness: R: 2 vs O: 0
Tremor: R: 2 vs O: 1
Parkinsonism: R: 1 vs O: 0
Agitation: R: 1 vs O: 5
Increased prolactin level: R: 0 vs O: 1
Blurred vision: R: 0 vs O: 1
Increased salivation: R: 0 vs O: 1
Anxiety: R: 1 vs O: 0
Sedation: R: 5 vs O: 3
Hypotension: R: 2 vs O: 0
Dizziness: R: 1 vs O: 1
Weight Gain: R: 1 vs O: 1
Difficulty swallowing: O:1 vs R: 0
Sexual dysfunction: O: 1 vs O: 0
Karagianis, 2009
HOCCC study
9 Canadian provincesProspectiveNR1 yearMean doses(SD) at 12 mo (mg/day)
Olanzapine: 12.8 (8.2)
Risperidone: 2.9 (1.7)
Quetiapine:375.6 (SD 293.6)
Clozapine: 332.8 (172.9)
schizophrenia or other related disordersOlanzapine vs risperidone vs quetiapine vs clozapine
Age (yrs), mean (SD) 43.4(11.6) vs 43.7 (11.5) vs 41.9 (11.1) vs 43.1 (12.4)
% female: 48% vs 48.4% vs 45.8% vs 14.3%
% Caucasian: 88.1% vs 84.7% vs 86.1% vs 94.7%
NR/NR/929266/NR/796Olanzapine vs risperidone vs quetiapine v clozapine
Proportion of treatment completers: 67.4% vs 62% vs 63.7% vs 55.6%, p=0.15
Olanzapine vs risperidone vs quetiapine v clozapine % of serious adverse events:
11.7% vs 8.9% vs 15.7% vs 21%
5 deaths in olanzapine group vs 1 from the other SGA group.
Olanzapine vs risperidone vs quetiapine
LS mean changes from baseline BMI were 0.7 (95% CI 0.1 to 1.2), 0.6 (95% CI −l;0.3 to 1.5) and −1.2 (95% CI −2.3 to −0.13). Olanzapine and risperidone groups had significantly higher increases in BMI( LS mean treatment effect 1.91 (95% CI: 0.41 to 3.42) and 1.86 (95% CI 0.13 to 3.58) respectively compared to quetiapine
LS mean weight change from baseline(Kg): 2.0 (95% CI 0.4 to 3.6) vs 1.2 (95% CI −1.3 to 3.8) and −2.8 (95% CI −6.1 to 0.4). Olanzapine and risperidone significantly ore likely to gain weight compared to quetiapine (LS mean difference 4.8 and 4.0 respectively)
Kim 2008
Korea
Comprehensive medical histories were collected from all available sources including patients, informants, and hospital medical recordsProspectiveNR2 yearsMean modal dose (mg/day)
Clozapine: 423.6±107.4
Risperidone: 7.6±2.9
Schizophrenia and comorbid alcohol use disorders (AUD)

Exclusion criteria: subjects with substance abuse other than alcohol, those with significant physical problems or organic mental disorders, and those with mental retardation
Clozapine/Risperidone

Age (y): 39.5±9.4/38.7±10.5
Gender (% male): 100/100
Ethnicity: NR
NR
67
67
6
NR
61 (25 clozapine, 36 risperidone)
Clozapine/Risperidone

Community survival (%): 52/25
Mean survival (d): 526.5 (95% CI 435.0–498.6)/420.4 (95% CI 342.2–498.6)
The survival curve for the clozapine group was significantly different from that of the risperidone group (log-rank test, df=1, P= .045)
NRStudy subjects were 100% male
Kilzieh 2008
United States
Electronic medical records database transformed into a data “warehouse” for data extractionRetrospectiveJanuary 1999 through December 2000NRNRSchizophrenia or schizoaffective disorderMean Age (y): 48.4±11.6
% Male: 91
Ethnicity: NR
NR
NR
495 (221 Olanzapine, 274 Risperidone)
NR
NR
495
Discontinuation rates:
Index medication trials: 73%
Olanzapine: 70%
Risperidone: 76% (P=0.12)

Higher discontinuation rate of risperidone: hazards ratio = 1.23; 95% CI 0.99–1.5

Median time (d) to discontinuation: 120 (95% CI 105–135)
Median time (d) to discontinuation (olanzapine): 150 (95% CI 120–180)
Median time (d) to discontinuation (risperidone): 90 (95% CI 71–109) olanzapine compared to risperidone, P=0.04

Self-discontinuation was the main method of discontinuation occurring in 48% of index trials, with no significant difference between olanzapine (50%) and risperidone (46%) (OR 0.86, 95% CI 0.60–1.23)
Switching between 2 agents as a form of discontinuation: 25% of index trials
More switching in risperidone (30% ) than olanzapine (20%) (P=0.01; OR 1.72, 95% CI 1.13–2.61)
Of patients who switched medication, 44% did so in the first month of trial. Observed more in risperidone (50%) than olanzapine (32%) (P=0.05)
NR
Koller, 2003
United States
Food and Drug Administration Med WatchRetrospective9 yearsNRRisperidone, haloperidolPatients prescribed study drugsMean age: 39.8 years
80% male
Ethnicity NR
NR/NR/NRNR/NR/NRRisperidone-associated hyperglycemia: N=131
Combined risperidone-haloperidol associated hyperglycemia: N=7
Haloperidol-associated hyperglycemia: N=13
Reports of acidosis with absence of hyperglycemia: N=11
# Patients with serious adverse events:
Acidosis-ketosis: 26
NMS-Like Symptoms: 12
Pancreatitis: 4
Death: 4
Koro, 2002
UK
England and Wales-based General Practice Database, Bristol-Myers Squibb, MEDTAPRetrospective30 monthsNROlanzapine: dose range NR
Risperidone: dose range NR
Conventional antipsychotics
SchizophreniaMean age: 51 years
60% Male
3.5 million/18,309/88660/0/8866NROdd of developing hyperlipidemia: compared with no antipsychotic exposure:
olanzapine: (OR, 4.65; 95% CI, 2.44–8.85); P<.001 vs risperidone: (OR, 1.12; 95% CI, 0.60–2.11); P=.72
compared with use of conventional antipsychotics:
olanzapine: (OR, 3.36; 95% CI, 1.77–6.39); P<.001 vs risperidone: (OR, 0.81; 95% CI, 0.44–1.52); P=.52
Koro, 2002b
UK
United Kingdom based General
Practice Research Database
RetrospectiveNRNROlanzapine: dose range NR
Risperidone: dose range NR
Conventional antipsychotics
Patients with prescriptions for both schizophrenia and diabetesMean age: 51 years
62.5% Female
3.5 million/3.5
million/19,637
0/0/19,637NROdds ratio of risk of developing diabetes:
Olanzapine vs non-treated 5.8; 95%CI: 2.0–16.7
Olanzapine vs typical APs: 4.2; 95%CI: 1.5–12.2
Risperidone vs non-treated: 2.2; 95%CI: 0.9–5.2
Risperidone vs typical APs: 1.6; 95%CI: 0.7–3.8
Kraus, 1999
Germany
Max Planck Institute of PsychiatryRetrospective4 weeks1 weekClozapine: 170 mg/day
Olanzapine: 13 mg/day
Haloperidol: 5 mg/day
SchizophreniaMean age: 37 years
43% Female
NR/NR/NRNR/NR/44Mean scores at endpoint; p value from baseline clozapine:
 weight: 71.0 kg; P=0.001
 leptin: 10.7 ng/ml; P=0.004
olanzapine:
 weight: 70.6 kg; P<0.001
 leptin: 10.1 ng/ml; P=0.006
haloperidol:
 weight: 64.2 kg; P=0.94
 leptin: 7.0 ng/ml; P=0.54
no treatment:
 weight: 69.1 kg; P=0.63
 leptin: 7.3 kg; P=0.86
NR
Kurz, 1995
Austria
Single center
Active control
First-time clozapine usersMean weeks: clozapine=23.2, haloperidol=5.2 23.2 weeksClozapine 193.7 mg
Haloperidol 12.8 mg
Anticholinergics
Beta blockers
Tardive dyskinesiaMean age=30.3
63.6% male
Race NR
NR
NR
151
NR
NR
Unclear
NRSigns of TD: clozapine=5 cases (all had already shown symptoms at baseline); Haloperidol=0
Lambert, 2005
Australia
Medical record reviewRetrospective1998 to 200018 monthsRisperidone: 2.7mg/day (non-affective psychosis) and 2.5mg/day (affective psychosis)
Olanzapine: 10.3mg/day (non-affective psychosis) and 9.8mg/day (affective psychosis)
Experiencing an episode of psychosis, non- affective psychosis, or affective psychosisMean age (years): 21.7
66% male
NR/NR/367NR/NR/367Treatment variables
Within affective group, those taking olanzapine had a significantly longer duration of treatment than those taking risperidone (p=0.02)
Outcome measures (non-affective psychosis)
No significant differences were noticed between groups on the CGI-S, GAF, and SOFAS 112 people (56.6%) in the risperidone group and 28 people (58.3%) in the olanzapine group reached full remission of positive symptoms
Outcome measures (affective psychosis)
There was a significantly better response to olanzapine compared to risperidone measured by the CGI- S score at endpoint (p=0.002), however scores on the CGI-BP, GAF, and SOFAS were not significantly different
Extrapyramidal side effects overall (p<0.001), especially parkinsonism (p<0.001) and akathisia (p=0.015) occurred more often in the risperidone group. More patients on risperidone experienced prolactin elevation (p=0.014), while weight gain was more prevalent with olanzapine users (p<0.001)
Lambert, 2005
SOHO (secondary publication) 6-month tolerability results Europe (Denmark, France, Germany, Greece, Ireland, Italy, the
Same as Haro 2005Same as Haro 2005Initial recruitment period of 9/1/00-12/31/016 monthsSame as Haro 2005Subset of patients who were only receiving one antipsychotic after the baseline visitMean age=40
56.6% male
Ethnicity NR
10,972/8400/7436NR/NR/7436NRMean weight change (kg)/adjusted difference compared to olanzapine (95% CI)
Olanzapine: 2.4
Risperidone: 1.4/−1.0 (−1.3, −0.7)
Quetiapine: 0.6/−1.2 (−1.6, −0.7)
Amisulpride: 1.4/−0.7 (−1.4, 0.0)
Clozapine: 2.3/0.1 (−0.6, 0.7))
Oral typical: 1.1/−1.3 (−1.8, −0.8)
Depot typical: 1.1/−0.9 (−1.5, −0.3)

Mean BMI change (kg/m2)/adjusted difference compared to olanzapine (95% CI)
Olanzapine: 0.9
Risperidone: 0.5/−0.4 (−0.5, −0.3)
Quetiapine: 0.2/−0.4 (−0.6, −0.2)
Amisulpride: 0.5/−0.2 (−0.5/0.0)
Clozapine: 0.8/0.0 (−0.3, 0.2)
Oral typical: 0.4/−0.5 (−0.7, −0.3)
Depot typical: 0.4/−0.4 (−0.6, −0.1)
Lambert, 2006
United States
Veterans Health Administration of the Department of Veterans Affairs (VA)RetrospectiveOctober 1, 1996 to
September 30, 2001
NROlanzapine
Risperidone
Quetiapine
Haloperidol
SchizophreniaOlanzapine/Risperidone/ Quetiapine/Haloperidol Mean age (years): 50.3/51.1/50.6/52
% male: 94.1/93.2/91.7/95.1
% African American: 28.8/30.8/21.2/39.4
% Hispanic: 6.8/4.8/4.1/5.4
NR/NR/15767NR/NR/15767There were no significant differences between groups in regards to increased risk of developing diabetes.
When analyses were reproduced, including those excluded previously due to having been exposed to antipsychotic agents during the prior 12-week period, there was an increased relative risk of developing diabetes for all second-generation antipsychotics except for quetiapine. In this analysis, the relative risk associated with olanzapine was significantly greater than that associated with risperidone (P=0.02).
NR
Lambert, 2005
United States
California MedicaidRetrospectiveJuly 1, 1997 to December 31, 2000NAMore than 12 weeksSchizophreniaNR129341/34337/12637NR/NR/12637NROdds ratios for conditional logistic regression model predicting development of hyperlipidemia
12-week exposure: n, OR, p(95% CI)
clozapine: 879, 1.16, 0.07(0.99–1.37)
olanzapine: 3322, 1.20, 0.00 (1.08–1.33)
quetiapine: 322, 1.01, 0.92(0.78–1.32)
risperidone: 2612, 1.00, 0.98(0.90–1.12)
24-week exposure: n, OR, p(95% CI)
clozapine: 766, 1.22, 0.03(1.03–1.45)
olanzapine: 2935, 1.24, <0.0001 (1.12–1.38)
quetiapine: 243, 0.83, 0.25(0.61–1.13)
risperidone: 2365, 1.01, 0.91(0.90–1.13)
52-week exposure: n, OR, p(95% CI)
clozapine: 603, 1.20, 0.06(0.99–1.46)
olanzapine: 2036, 1.17, 0.01 (1.04–1.32)
quetiapine: 140, 0.80, 0.27(0.53–1.20)
risperidone: 1819, 0.94, 0.34(0.83–1.27)
Lee, 2006 IC-SOHO sub-study in Asian country participants 12-month outcomes Korea, Taiwan and MalaysiaSame as Dossenbach 2004Same as Dossenbach 2004NR12 monthsSame as Dossenbach 2004IC-SOHO patients from participating Asian countriesMean age=34.7 years
50% male
100% Asian
1256/NR/898100 (11%)/0 lost to fu/analyzed unclearResponse rates (overall CGI-S score improved by ≥ 2 points from a baseline score of ≥ 4, or improved by ≥ 1 point from a baseline score of 3):
Olanzapine=76.3%
Risperidone=72.7%
Typical antipsychotics=50%
OR of response for typical agent vs olanzapine: 0.38 (p=0.010) (CI NR)
Tardive dyskinesia
% patients:
olanzapine=7.9%
risperidone=13.3%
 typicals=13%
OR (95% CI):
risperidone vs olanzapine=1.04(0.34–3.14)
 typicals vs olanzapine=4.23(1.02, 17.47)
 typicals vs risperidone=4.08(0.83, 19.94)

Weight increase of ≥ 7%
% patients:
olanzapine=51.4%
risperidone=29.8%
 typicals=20.5%
OR (95% CI)
risperidone vs olanzapine=0.38 (0.21, 0.68)
 typicals vs olanzapine=0.27 (0.12, 0.64)
 typicals vs risperidone=0.72 (0.29, 1.81)
Lee, 2002
United States
Database: Protocare Sciences’ administrative claims and enrollment infoRetrospectiveIndex dates of patients occurred during a 27-month period (1997–1999).

Mean duration of therapy:
AAPs: 126.1 days Typical
APs: 108.34 days
Patients were observed 365 days after their index dates.Clozapine
Olanzapine
Quetiapine
Risperidone
Typical APs
Mean doses NR
Patients aged 18–65 selected by first (index) AP/AAP prescription between Sept 1997–Dec 1999; excluded those who filed a claim for an AP/AAP within 180 days, or filled a Rx for a diabetes medication or had a DM diagnosis within 365 days before index date. Also excluded patients using concomitant AP meds on index date.Mean age 44
41.4% male
Ethnicity NR
NR
2315
2315
AAPs n=1334
Olanzapine n=513
Risperidone n=750
Clozapine n=5
Quetiapine n=66
Typical APs n=981
NR
NR
2315 analyzed
NRAdjusted odds (95%CI) of diabetes onset within 1-year after index date:

Atypicals vs typicals: 1.01 (0.61–1.67)
Olanzapine vs typicals: 0.86 (0.43–1.73)
Risperidone vs typicals: 1.07 (0.61–1.89)
Olanzapine vs risperidone 0.79 (0.38–1.61)
Leon, 1979
Colombia
Hospital Psiquiatrico, ColombiaRetrospective6 weeks3–4 yearsNRSchizophreniaMean age: 30.6 years
58% male
Ethnicity NR
NR/NR/50NR/NR/39Mean number of required re-hospitalizations:
clozapine: 1.89 vs chlorpromazine: 3.52; P<0.01
Average time spent in hospital:
clozapine: 44.8 days vs chlorpromazine: 272.8 days; P<0.05
Average mean time for re-admission:
clozapine: 260 days vs chlorpromazine: 229
NR
Leslie, 2004
United States
Department of Veteran AffairsRetrospective3 monthsNRClozapine, olanzapine, quetiapine, risperidone: mean doses NRSchizophreniaNR/NR/NR56,849/56,849/56,8490/0/56,849NR7.3% diagnosed with diabetes will on treatment
Highest risk:
clozapine: 2.03%, quetiapine: 0.80%, olanzapine: 0.63%, risperidone: 0.05%
Lin, 2006
Taiwan
Chart reviewsRetrospective7/1/01-6/30/022 yearsClozapine, risperidone, typical antipsychoticsSchizophrenia82% male
Mean age=39.2 years
100% Taiwanese
NR/NR/38283 (22%)/NR/382Typical antipsychotic vs clozapine vs risperidone:

360 days follow-up period
Mean time to rehospitalization (days): 244 vs 240 vs 262, p=NS
Event rate: 49.6% vs 44.3% vs 43%, NS

720-day follow-up period
Mean time to rehospitalization (days): 378 vs 403, vs 426, NS
Event rate: 57.7% vs 49.2% vs 53.1%, NS
NR
Liperoti 2009
USA
SAGE database containing MDS; data is from 1581 nursing homes in 5 US statesRetrospectiveJan 1998–Dec 20006 months following first use of any antipsychotic.Atypical antipsychotics (N=6524)
Risperidone: n=4406
Olanzapine N=1563
Quetiapein N=497
Clozapine N=59
Conventional antipsychotics (N=3205), most frequently haloperidol (N=1413) and phenothiazines (N=546)
Mean dose NR.
Nursing home residents with dementia, aged 65+ who were new users of antipsychotics. Excluded comorbid schizophrenia.Mean age: 84
72% male
90.7% White
8.4% Black
61,781 exposed 9,729 eligible (1st-time monotherapy users) All 9729 eligible were included.No withdrawals.
Loss to followup NR.
9729 analyzed.
NRRisk of mortality is 26% greater with haloperidol vs atypical antipsychotics.
Effect of conventional APs on increased mortality seen only in non-Alzheimer’s dementia; absent among those with Alzheimer’s dementia.
Mortality during 6 months after index prescription, crude incidence per 100 person-years: Atypical antipsychotics: 40.0
Conventional antipsychotics: 54.3
HR for conventional vs atypical APs adjusted for age, race/ethnicity, gender, BMI, ADL score, Cognitive Performance Scale score, severity of behavioral symptoms, cardiovascular and cerebrovascular comorbidities, and use of concomitant medications (including cardiovascular drugs, aspriin/sntiplatelets/anticoagulants, benzodiazepines, and antidepressants:
Residents with Alzheimer’s Disease, HR = 1.02 (95%CI 0.75–1.39)
Residents with other dementias (non-Alzheimer’s), HR = 1.31 (95%CI 1.14,1.50)
Haloperidol vs risperidone, adjusted HR: 1.31 (95%CI 1.13–1.53).
Mortality was similar among AAPs.
Lucey, 2003
Ireland
Irish Risperidone Olanzapine
Drug Outcomes in Schizophrenia
RetrospectiveMean duration: 37.8–40.5 daysNRrisperidone: 4.2 mg/day
olanzapine: 12.9 mg/day
Schizophrenia, schizoaffective disorderMean age: 37 years
55.5% Male
Ethnicity NR
NR/396/3940/0/396Hospital Stay:
% discharged on or before day 120:
R 95% vs O 94% (NS)
Mean length of study duration:
O 30 days vs R 26 day (p=0.27)
Duration of hospital stay:
O 40.5 vs R 37.8 (p=0.90)
Distribution function curve of time to discharge:
‘similar’, p = 0.0.54
NR
Madhusoodanan, 1999
United States
St. John’s Episcopal HospitalRetrospective4 monthsNRMean daily doses:
risperidone(N=114): 3mg
olanzapine(N=37): 10mg
schizophrenia, schizoaffective disorder, dementia, bipolar disorder, major depressive w/psychotic features, delusional disorderMean age: 71 years
60.5% Female
Ethnicity NR
NR/NR/15122%/NR/151% of patients who responded to treatment: R: 78% vs O: 75% CGI scores:
Very much/much improved: R: 78% vs O: 75%
Minimally improved: R: 56% vs O: 24%
No change: R: 20% vs O: 8%
Adverse events reported:
R: 20%; EPS, tremor, sedation, hypotension, diarrhea, tardive dyskinesia, chest pain, anxiety, restlessness, itching, insomnia and fall
O: 16%; sedation, EPS, postural hypotension
McIntyre, 2003
Williams, 2006
Canada

Canadian National Outcomes Measurement Study in Schizophrenia (CNOMSS)
Naturalistic: 32 university and community sites across CanadaProspectiveJune 1999 and November 2000Olanzapine=333
Quetiapine=324
Risperidone=280 (days)
Olanzapine 14.7 mg
Quetiapine=324mg
Risperidone=3.5 mg
Consecutive outpatients with schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis NOSMean age=36.8
67.9% male
Race NR
NR
NR
243
(Olanzapine=109, Quetiapine=23, Risperidone=111)
NR
NR
243 analyzed
Admission to hospital for any reason: n/N (%)
Initial assessment to year 1; year 2

Clozapine: 9/59 (15.2%); 12/51 (23.5%)
Olanzapine: 7/87 (8%); 9/70 (12.8%)
Quetiapine: 5/20 (25%); 5/16 (31%)
Risperidone: 10/97 (97%); 14/80 (17.5%)
Mean weight gain (kg)
Olanzapine=3.72
Quetiapine=7.55
Risperidone=1.62
≥ 7% weight gain (% pts)
Olanzapine=24.1%
Quetiapine=55.6%
Risperidone=23.7%
Quetiapine vs risperidone=OR 3.62, 95% CI 1.02 to 12.83
≥ 10% weight gain (% pts)
Olanzapine=18.5%
Quetiapine=38.9%
Risperidone=13.2%
Quetiapine vs risperidone=OR 3.91; 95% CI 1.02 to 15.08
Medved, 2009
Croatia
cohort of patients admitted to the Department of Psychiatry, Zagreb University Hospital CentreProspective2004 to 20073 monthsOrally administered olanzapine 5–20 mg/day or risperidone 2–5 mg/day for 3 months (±1 week) during 3–6 weeks of hospital treatment and followed by outpatient treatment.

Mean olanzapine dose (SD): 11.51 (3.9)
Mean Risperidone dose (SD): 3.16 (1.09)
Patients who were previously unmedicated (no antipsychotic medication) prior to admission and were diagnosed with DSM-IV schizophrenia spectrum disorders (DSM-IV criteria met for schizophrenia, schizoaffective disorder or delusional disorder, and no other neurological diseases, mental disorders, drug and alcohol abuse and eating disorders). Patients with menstrual cycle irregularities, pregnant, lactating or required treatment with medications other than diazepam and clonazepam for occasional insomnia were not included.Mean age (SD): 31.07 (7.86)
100% female
100% Caucasian
NR/NR/940/0/94NROlanzapine: 10 (19%) drowsiness; 1 (2%) extrapyramidal syndrome (EPS); 1 (2%) edema
Risperidone: 6 (16%) drowsiness; 2 (5) galactorhea; 1 (2.4%) EPS

27% patients with metabolic syndrome after 3-month compared to 15% of patients at baseline.
Increase in BMI (SD) of 2.44 (3.01).
“BMI was found to be a significant predictor of metabolic syndrome after second-gereration antipsychotics treatment”; P<0.001
Meyer, 2002
United States
Oregon State HospitalRetrospectiveJuly and August 19991 yearrisperidone (N=47): 4.5 mg/day
olanzapine (N=47): 16.7 mg/day
Schizophrenia, schizoaffective disorderMean age:44.5 years
41% 87% Male
Ethnicity NR
NR/396/394Withdrawn=N/A (retrospective)
Lost to follow-up=N/A (retrospective)
Analyzed=94
Fasting triglyceride levels at one year: R: mean increase of 29.7 mg/dL vs O: 88.2 mg/dL
Weight increases at one year: R: 11.7–13.9lb vs O: 15.0–26.0lb
Triglycerides: O: + 104.8 mg/dL vs R: +31.7 mg/dL (P=.037)
Cholesterol: O: +30.7 mg/dL vs R: +7.2 mg/dL (P=.004)
Glucose: O: +10.8 mg/dL vs R: +0.74 mg/dL (P=.030)
Miller, 1998
United States
Innsbruck University Clinics, AustriaRetrospective≥3 monthsNRclozapine: 425.6 mg/day
risperidone: 4.7 mg/day
conventional antipsychotics: 476.5 mg/day
Schizophrenia, schizoaffective disorder, personality disorder, paranoid subtypeMean age: 36.6 years
57.5% Male
White: 71.7%
Black: 2.6%
Hispanic: 3.8%
Asian: 1.9%
NR/NR/NR0/0/106Simpson-Angus Scale scores:
Akinesia>0: C: 17.1% vs R: 30.4% vs Conventionals: 38.1%
Arm dropping>0: C: 12.2% vs R: 30.4% vs Conventionals: 35.4%
Gait>0: C: 4.9% vs R: 21.7% vs Conventionals: 23.8%
Salivation>0: C: 36.6% vs R: 8.7 vs Conventionals: 4.8%
Tremor>0: C: 19.5 vs R: 21.7% vs Conventionals: 40.5%
Point prevalence of Akathisia: C: 7.3% vs R: 13% vs Conventionals: 23.8%
Point prevalence of Rigidity: C: 4.9% vs R: 17.4% vs Conventionals: 35.7%
Point prevalence of Cogwheeling: C: 2.4% vs R: 17.4% vs Conventionals: 26.2%
Modai, 2000
Israel
Database: Sha’as Menashe Mental Health Center (Israel)Unclear1/91 to 8/97NRClozapine
Other psychiatric agents (non-clozapine treated)
SchizophreniaNR
NR
NR
NR
5479
5479
NR
NR
5479 (Clozapine=561 vs Non-clozapine=4918)
NRSudden death=6 (1.07%) vs 14 (0.28%); p<0.01
Disease-related death=2 (0.35%) vs 86 (1.75%); p<0.05
Total death=10 (1.78%) vs 105 (2.13%); NS

Suicide
2 (0.35%) vs 5 (0.10%); NS
Mohamed, 2009
United States
Database: National administrative databases; and the Veterans Affairs Drug Benefit Management System filesRetrospective20062 year follow-upLong-acting injectable risperidone or oral antipsychoticsAll veterans seen at Veterans Affairs medical centers nationally who received a prescription for any new antipsychotic medication during fiscal year 2006 and had a diagnosis of schizophrenia. Prescriptions were considered new if there were no prescriptions for the drug during the last 6 months of fiscal year 2005.32.4% at age 40–49 years
48.9% at age 50–64 years
8.6% at age >65 years

93.4% male

21.5% Black
5.1% Hispanic
1.1% Other
20% unknown race
11821/11821/118210/0/11821Hazard ratio for discontinuing antipsychotics as compared to long acting injectiable risperidone:

Aripiprazole: 2.76; P=0.0001
Clozapine: 0.37; P=0.0001
Conventional: 0.83; P=0.0003
Olanzapine: 0.83; P=0.0017
Quetiapine: 0.78; P=0.0001
Risperidone: 0.83; P=0.0002
Ziprasidone: 0.96; P=0.5516
NR
Moisan, 2005
Canada
Database from the Prescription Drug Insurance Plan administered by the Quebec Health Insurance BoardRetrospectiveJanuary 1, 1997–August 31, 1999NROlanzapine
Risperidone
All drug beneficiaries who had received at least one prescription of an atypical antipsychotic drug during the time period and was under the age of 65.% in each age group:
0–29 years=20.4
30–44 years=43.8
45–59 years=29.9
60–64 years=6.0
% male: 51.5
38043/19582/19582NR/NR/19582Those taking olanzapine were more likely to need to be started on a diabetic and/or lipids medication than those taking risperidoneNR
Montes, 2003
Spain
Sub-group Analysis from Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapine (EFESO)
Multicenter ControlledSubjects that required antipsychotic treatment for a first episode of schizophrenia, with an evolution of the illness of less than one year and who were not over the age of 40. Choice of new drug was made by the treating physician.6 monthsOlanzapine 13.5 mg
Risperidone 5.4 mg
Haloperidol 12.4 mg
High potency antipsychotics
Low potency antipsychotics
Benzodiazepines
Anticholinergics
Antidepressants
Mood stabilizers
Weight gainMean age=24.2
64.8% male
Race NR
NR
NR
182
45 (24.7%) withdrawn 24 (13.2%) lost to fu 182 analyzedNRWeight gain (% patients)
Olanzapine=15 (13.2%)
Risperidone=1 (3.2%)
Haloperidol= 0
p<0.05 for olanzapine > risperidone and haloperidol groups
First Episodes
Mullins 2008
Maryland
All pharmacy and medical service encounter and fee-for-service claims from the Maryland Medicaid FFS and HealthChoice programsRetrospectiveJanuary 1, 2001 to December 31, 2003NRMaryland Medicaid recipients aged 18–64 having a claim for schizophrenia any time during the three year study period for any of the 5 atypicals (aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone)Aripiprazole/Olanzapine/Quetiapine/Risperidone/Zipr asidone

Age Group (%)
18–39: 39.9/43.5/41.9/41.7/49.9
40–54: 48.4/44.5/47.1/46.5/42.1
55–64: 11.7/12.0/11.0/11.8/8.0

Gender (% male)
52.2/54.1/47.6/46.9/49.1

Ethnicity
White: 53.6/39.1/47.5/38.5/48.7
Black: 46.4/60.9/52.5/61.5/51.3
NR
NR
5898 (1705 olanzapine, 1580 risperidone, 1467 quetiapine, 700 ziprasidone, 466 aripiprazole)
NR
NR
5898 (1705 olanzapine, 1580 risperidone, 1467 quetiapine, 700 ziprasidone, 466 aripiprazole)
Hazard ratios of discontinuation (95% CI), P value:
Olanzapine: reference
Aripiprazole: 1.047 (0.919–1.193), 0.4911
Quetiapine: 1.130 (1.039–1.230), 0.0044
Risperidone: 0.973 (0.897–1.055), 0.5014
Ziprasidone: 0.990 (0.891–1.100), 0.8514
Age: 0.997 (0.994–1.000), 0.0348
Black: 1.058 (0.994–1.127), 0.785
Male: 0.899 (0.845–0.957),0.0008
Psychiatric hospitalization: 1.276 (1.192–1.367), <0.0001
Concurrent medications: 0.225 (0.210–0.241), <0.0001

Adjusted medication continuation/discontinuation rates:
Median time to discontinuation (d)/180-day continuation rate (%)/365-day continuation rate (%)
Aripiprazole: 58/19.1/9.0
Olanzapine: 59/20.6/10.0
Quetiapine: 54/16.8/7.4
Risperidone: 61/21.5/10.7
Ziprasidone: 59/20.9/10.3
NR
Novick, 2005
SOHO (secondary publication)
Europe
Prospectively collected, multicenter study dataProspective6 mo (interim analysis of planned 3-yr term)NROlanzapine 11.8 mg/day (SD 5.7)
Risperidone 4.9 mg/day (SD 2.7)
Quetiapine 375 mg/day (SD 201)
Clozapine 235 (SD 134)
Schizophrenics receiving antipsychotic monotherapyMean age 39.6 yrs
57% male
Ethnicity NR
10972/8057/6931 (olanzapine, risperidone, quetiapine and clozapine cohorts only)765/NR/6931 (olanzapine, risperidone, quetiapine and clozapine cohorts only)NRProportion of pts reporting weight gain:
O 2993/4428 (67.6%) v R 946/1617 (58.5%) v Q 300/610 (49.2%) v C 157/276 (56.9%)

Subgroup: concomitant medication use - proportion of pts reporting weight gain:
O 1772/2546 (69.6%) v R 581/972 (59.8%) v Q 183/373 (49.1%) v C 118/183 (64.5%)
Ollendorf, 2004
United States
Database:
PharMetrics Patient-Centric
Database
Retrospective1995–2001
Mean duration of therapy was 9 months in both typical AP and AAP groups; mean number of prescriptions was higher in AAP group: 8.5 vs 6.6, p<0.0001
Minimum of 3 months; mean 435 daysOlanzapine n=937
Risperidone n=690
Quetiapine n=164
Clozapine n=35
Mean dose NR
Patients with ≥1 medical claims with a diagnosis of schizophrenia, as well as ≥1 paid pharmacy claims for an AP medication during 1996–2001; the first observed antipsychotic pharmacy claim in this period was the index date. All medical and pharmacy claims were then compiled for these patients for the exposure period. Patients who used an AP or typical AP in the 6 months prior to the index date, or had evidence of DM within 12 months prior to the index date were excluded.Mean age 39.1
48.2% male
Ethnicity NR
18,134
2443
2443
NR
NR
2443
NRPatients treated with AAPs had an increased risk of diabetes mellitus after 1 year, compared with typical APs: hazard ratio 1.17, 95% CI 1.06–1.30

No differences between olanzapine, risperidone, quetiapine, and clozapine were found on risk of diabetes.
This analysis controlled for total duration of therapy and number of prescriptions. Actual mean doses are not reported.
Opolka, 2003
United States
Medical claims data from the Texas Medicaid Management Information System and pharmacy claims data from the Texas Vendor Drug Program paid prescription claims databaseRetrospectiveJanuary 1, 1996 to August 31, 1999NRHaloperidol
Risperidone
Olanzapine
Schizophrenia, schizoaffective disorderMean age: NR
Gender: NR
45% White
39% African American
NR/NR/3583NR/NR/3583Adherence to index antipsychotic
Risperidone users were 15% less adherent than olanzapine users (30 days less use/study period, P<0.001)
Haloperidol users were 33% less adherent than olanzapine users (65 days less use/study period, P<0.001) and 21% less adherent than risperidone users (35 days less use/study period, P<0.001)
African Americans were 12% less adherent than whites (24 days less use/study period, P<0.001)
Mexican Americans were 13% less adherent than whites (25 days less use/study period, P=0.003) and 1% less adherent than African Americans (2 days less use/study period, P=0.838)
NR
Ostbye, 2004
United States
Database: AdvancePCS records on prescription drugs dispensed to beneficiaries (n=170030 from 50 states)Retrospective2000–200218 monthsPrimary exposure: subjects who filled prescriptions for any AAP at any time during the follow-up period. Primary control: subjects who filled prescriptions for typical AAPs during followup. Other control groups received antibiotics; antidepressantsSubjects for whom the first prescription for an exposure drug occurred after the 6-month lead-in period. The primary exposure group was subjects who filled prescriptions for an AAP in the followup period. The primary control group was subjects who filled prescriptions for typical APs in the followup period.Mean age 41.9
38.1% male
Ethnicity NR
NR
NR
170,030
NR
NR
170030
NRPrimary outcome was a new prescription filled for any antidiabetic drug during followup period, excluding those filled prior to the first prescription of an AP or AAP. Adjusted ORs (95% CI);
AAPs: 1.70 (1.58–1.83)
Typical APs: 2.08 (1.88–2.30)
Antidepressants: 2.12 (1.96–2.30)
Antibiotics: referent group
In subjects that used only one drug class during study period:
AAPs 0.86 (0.60–1.23)
Typical APs: referent group
Antidepressants 1.08 (0.81–1.45)
Antibiotics 0.68 (0.50–0.92)
Exposure classification is binary (did or did not receive prescription for each drug or class); dose and duration of treatment are not controlled for
Peacock, 1996
Denmark
Naturalistic: St. Hans Hospital; Copenhagen’s Municipal Psychiatric Hospitals in Glostrup and BallerupProspective1 yearNRClozapine
CAPD
SchizophreniaMean age=41.5
69.5% male
Race NR
NR
NR
200
42(21%) withdrawn
Lost to fu NR 158 analyzed (clozapine-=82, CAPD=76)
NRClozapine versus control:
Potentially new:
 Overall tardive dyskinesia (TD): relative advantage of clozapine=36% (95% confidence limits=21–50%; P<0.001)
 Oral TD (# cases): 9 vs 19; NS
 Extremity TD (# cases): 5 vs 22; P<0.001
TD 1-year follow-up
 Prior TD “disappeared” (# cases): 3 vs 1, P-value NR
 Prior TD “reappeared” (# cases): 2 vs 0, P-value NR
 New cases still present: clozapine=all 11, control=all but 1
 Further potentially new cases: 0 vs 4
Parkinsonian signs at first examination: 33% vs 61%; relative advantage of clozapine=28% (95% CL 15–41%, P<0.001)
Parkinsonian symptom severity (# patients with global score of ≥ 3): 8 vs 32, P<0.05
Parkinsonism source (# cases; relative advantage of clozapine, 95% CL):
 Rigidity: 0 vs 19; 19% (95% CL 11–27%, P<0.001)
 Tremor: 3 vs 11; 8% (95% CL 1–15%, P=0.05)
Psychic akathisia (% patients): 14% vs 40%; P<0.001
Motor akathisia (% patients): 7% vs 29%; P<0.001
Mild finger dystonia (# patients): 1 vs 10; P<0.05
Pelagotti, 2004
Italy
Inpatients to a hospital Psychiatric Unit or as outpatients to a Psychiatric Ambulatory Clinic.Retrospective15 May 2002 to 20 August 2002Median 11.9 monthsOlanzapine daily dose (mg) 13.3 (n=283)
Risperidone daily dose (mg) 5.7 (n=170)
Diagnosis of schizophrenia; ≥ 18 years; treatment with either olanzapine or risperidone at the date of enrollment; “Stable” therapy over the previous 4 months; Cumulative dose in this period of at least 80% of the respective defined daily doses (DDD values: olanzapine, 10 mg/day; risperidone, 5 mg/day).Mean age 40 years
61.8% male
Race NR
454/NR/144NR/NR/144Dropout rate in the primary analysis (with a follow-up of 7 months: 4 switches from olanzapine to risperidone versus 11 switches from risperidone to olanzapine, P = 0.01) and in the secondary analysis (with a follow-up longer than 7 months: 9 switches from olanzapine versus risperidone and 17 switches from risperidone to olanzapine; P = 0.004).NR
Peuskens 2009
Belgium
Participants were recruited from university hospitals, general and psychiatric hospitals and ambulatory practiceProspective2 yearsHaloperidol/Olanzapine/Risperidone

Mean treatment duration (d) based on 294 patients: 476±248/545±232/513±257
Haloperidol/Olanzapine/Risperidone

Mean dose (mg/d) based on 294 patients: 8.9±6.8/14±6/4.2±1.9
Adults diagnosed with schizophrenia or schizophreniform disorder and stabilized with haloperidol/haloperidol decanoate, olanzapine or risperidone monotherapy ≤ 1 month following discharge from full-time (maximum 6 month) hospitalization due to first episode of schizophrenia or psychotic relapseHaloperidol/Olanzapine/Risperidone

Age (y): 41.8±14.4/37.2±13.1/35.7±13.2
Gender (% male): 81/66/59
Ethnicity: NR
NR
NR
323
7
84
273 (1-year follow- up), 219 (2-year follow-up)
294/323 patients (91%) had ≥1 follow-up visit
Mean follow-up time of these 294 patients was 597±219 days (haloperidol), 630±186 days (olanzapine), and 640±200 days (risperidone), P=0.026

Haloperidol/Olanzapine/Risperidone
Continuation rates (%) after 2 years:
≥1 post-baseline visit: 88/92/92
Completers: 59/66/71
Stable: 47/68/61
Stable completers: 31/50/43
Allocated to treatment group but longer on another drug: 13/10/15
Switches: 39 (1–2 switches per patient)/23 (1–5 switches per patient)/31 (1–4 switches per patient)

Of 323 patients, 63% had no antipsychotic treatment switch or addition (stable patients)

There were 328 hospitalizations in 150 patients, of which 47 were hospitalized once (15%), and 83 were
hospitalized 2–8 times (26%)
165 were never hospitalized (51%); 28 had no follow-up data (9%)
Full-time hospitalization (%):
50/44/35 (NS)
Time to first rehospitalization (d):
123±168/215±189/209±184 (NS)
Duration of full-time hospitalization:
94±166/48±91/55±122

Social status, living environment and employment all remained stable over the 2-year study
Haloperidol/Olanzapine/Risperidone

Adverse Events

Weight gain
Mean baseline weight (kg):
79.2±12.5/74.9±13.9/75.3±14.2
Overall weight gain (kg):
NR/2.6/2.6
P<0.05 (olanzapine and risperidone)
Patients with weight gain >7% (%):
19/29/33
Weight gain of patients who dropped out from study: 1.5±4.1 kg/year
Weight gain of patients who remained in study: 1.7±9.0 kg/year

5 patients died
Sample size for haloperidol group was small, plus the group differed from the other groups in marital, institutionalized, and educational status
Philippe, 2005
France
Principal public psychiatric care units in FranceProspective1993 to 2002Nine yearsConventional antipsychotics
Risperidone
Olanzapine
Clozapine
Amisulpride
ICD-10 criteria for schizophrenia and to be between 18 and 64 years old Patients hospitalized for more than 1 year were excludedMean age 39.4 years
Male 64%
Ethnicity NR
NR/NR/3470NA/NA/3470At baseline, 2.2% of schizophrenic patients in the study cohort already had a diagnosis of diabetes vs.. an age and gender matched sample of the general population (1.5%).
Incidence of diabetes from 1993 to 2002
Conventional antipsychotic 2.8%
Risperidone 2.4%
Olanzapine 2.7%
Clozapine 2.1%
Amisulpride 2.4%
The standard mortality ratio was 3.6 (95% confidence intervals: 3.3 and 4.0), indicating a risk of death for schizophrenic patients in the study between three and four times higher than that of the general population.
Procyshyn, 1998
Canada
Chart review from Riverview Hospital in British ColumbiaRetrospective6 weeksNRMean Doses: risperidone: 5.3mg/day vs olanzapine: 14.5mg/dayAged ≤ 65 years, schizophrenia or schizoaffective disorder, discharged from hospital or ≥120 days follow-up in hospital, Types of Schizophrenia: catatonic, disorganized, paranoid, undifferentiated, residual, schizoaffective disease, other schizophreniaMean Age: 37 years
57.5% Male
Ethnicity NR
2339/1901/1345
Risperidone: N=924, Olanzapine: N=977
300/0/1345NRNumber of Patients Discontinued: Due to Side Effects:
R: 36(4%) vs O: 23(2%); P=0.70

Number of patients who experienced AE: R: 123(13%) vs O: 109(11%); P=0.20
Body as a whole: R: 8(0.9%) vs O: 13(1.3%); P=0.30
Central and peripheral nervous system: R: 73(7.9%) vs O: 56(5.7); P=0.06
Psychiatric: R: 45(4.9%) vs O: 40(4.1); P=0.40
Gastrointestinal: R: 21(2.3%) vs O: 13(1.3%); P=0.10
Metabolic and nutritional: R: 1(0.1%) vs O: 17(1.7%); P=0.04
Others: 27(2.9%) vs O: 17(1.7%);
Rascati, 2003
United States
Database: Texas Department of Health Medicaid ProgramRetrospectiveJanuary 1996 through August 19991 yearolanzapine: 12.87mg/day
risperidone 4.40mg/day
Schizophrenia or schizoaffective disorderMean age: 41.43 years
53% female
42% Caucasian, 34% African-American, 14% Hispanic, 0.97% Asian, 0.24% Native American, & 8.32% other
NR/NR/2885NR/NR/2885% who discontinued medication:
olanzapine=8.87%
risperidone =14.5%
Affects on medication choice:
Region: Increase likelihood of being prescribed olanzapine by 3% to 5% when in Austin, Lubbock or Dallas vs decreased likelihood by 3% when in San Antonio or Houston
Comorbid diagnosis: Having nonorganic mental illness as a comorbid diagnosis decreased likelihood of being prescribed olanzapine by 2% and having diabetes as a comorbid diagnosis also decreased likelihood of being initiated on olanzapine by 3%
Previous medication use: for each antipsychotic used in the pre-period the likelihood of being started on olanzapine increased by 3.5%. If an atypical was used in the pre-period the likelihood of being initiated on olanzapine increased by 8%
Schizophrenia related costs:
History of clozapine use was associated with an increase of $3158 (US) per year
History of depot antipsychotic use was associated with an increase of $1645 (US) per year
Total health care costs:
Previous hospitalization or history of clozapine use was associated with an increase of $3424 (US) per year and $2451 (US) per year, respectively
NR
Ray, 2009
United States
Computerized files of Tennessee MedicaidRetrospectiveJanuary 1, 1990 through December 31, 2005Median followup of 2.2 years for nonuser of antipsychotic drugs
Median 2.9 years for current user
Antipsychotic Drugs vs no usePersons 30–74 years of age enrolled in Tennessee Medicaid for at least 730 days (gaps of <7 days were allowed) and have been eligible for full pharmacy benefits and made regular use of medical care (defined as having had at least one filled prescription and one outpatient visit in each of the 2 preceding years); at least 1 qualifying day of use of antipsychotic drugs during the study periodMean age: 45.7 years
34.8% male
70.5% white
NR/NR/186600 nonusers and 93300 current user of antipsychotic drugs at cohort entryNA/NA/186600 nonusers; 44218 users of typical antipsychotic drugs; 46089 users of atypical antipsychotic drugsNRThe risk of sudden cardiac death increased with an increasing dose among current users of typical or atypical antipsychotic drugs (given in figure).
Users of the typical agents: incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for persons taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001 for dose–response relationship).
Users of the atypical drugs: the incidence-rate ratios increased from 1.59 (95% CI, 1.03 to 2.46) for persons taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P=0.01 for dose–response relationship).
Remington, 2001
Canada
Hospital records from the Schizophrenia and Continuing Care Program at the Centre for Addiction and Mental HealthRetrospective≥18 months (1993–1995)NROral or depot conventional antipsychotic
Clozapine
Risperidone
SchizophreniaOral Conventional/Depot Conventional/Clozapine/Risperidone
Mean age (years): 31.7/36.5/33.4/31.7
% male: 55/55/66/53
314/66/66NR/NR/NRNo significant differences were found between groups for number of hospital visits, days in hospital, or emergency room visits. Clozapine takers had a higher number of doctor visits compared to those taking either form of conventional antipsychotic, while risperidone takers had a higher number of doctor visits compared only to those taking oral conventional antipsychotics.
CGI scores were significantly improved over the 18 months for those treated with clozapine, risperidone, and depot conventional antipsychotics versus oral conventional antipsychotics.
NR
Ren, 2006
United States
Database: VA National administrative data and VA pharmacy benefits management strategic healthcare groupRetrospectiveOctober 1, 1998 through September 30, 19991 yearOlanzapine
Risperidone
Schizophrenia either paranoid type, disorganized type, catatonic type, undifferentiated type, residual type, schizophreniform disorder or schizoaffective disorderOlanzapine/Risperidone:
Mean age (years)=50/50.5
% male=94.7/94.7
% Caucasian=43.7/43.9
% African-American=31.5/33.9
% Hispanic=6.9/4.7
% other ethnicity=17.9/17.6
NR/NR/7144NR/NR/NRIncidence of comorbid conditions:
Those initiated on risperidone had more overall comorbid conditions (2.79 vs 2.68; P<0.05) and more medical comorbid conditions (1.53 vs 1.44; P<0.05) than olanzapine initiators
Incidence of concomitant medications
Those initiated on olanzapine used more mood stabilizers (14.45% vs 12.42%; P<0.05) and more overall number of drugs for psychiatric conditions (0.78 vs 0.73; P<0.05) than risperidone
Incidence of hospitalizations
No difference was found between the treatment groups regarding individuals having at least one psychiatric hospitalization
Incidence of discontinuation
Initiating with olanzapine decreased the incidence of discontinuation by 12%, when adjusted for sociodemographic and clinical information
NR
Rettenbacher, 2006
Austria
Laboratory measurements of included subjectsProspectiveNR4 weeksOlanzapine
Clozapine
Amisulpride
Ziprasidone
SchizophreniaAge range: 18–65 yearsNR/NR/NRNR/NR/35No significant differences were found between clozapine and olanzapine-treated patients regarding changes in scores of BMI and serum lipids (P>0.2).NR
Ritsner, 2006
Ritsner, 2004
Israel
Sha'ar Menashe Mental Health Center Case RegisterProspectiveNR1 yearOlanzapine 15.2 mg/day
Risperidone 4.4mg/day
Typical antipsychotics mean dose NR
Schizophrenia diagnosed based on DSM-IV criteria; age 18–60 yearsITT population:
Mean age=39.6 years
76.7% male
Race NR

PP population (n=124)
Mean age=40.0 years
78.2% male
Race NR
150/136/1339 (6.8%) withdrawn
4 (3%) lost to fu
124 analyzed
Q-LES-Q index (% change from baseline estimated from Figure 2): risperidone= +3.5% vs olanzapine= +14% vs first-generation agents= +6% vs combined therapy= −4%; 2-way ANCOVA test of treatment group effect: F=3.1, p=0.029; effect size for risperidone vs olanzapine= −0.57

Physical health index (% change estimated from Figure 2): risperidone= +5% vs olanzapine= +17% vs first-generation agents= +14% vs combined therapy= −2%; 2-way ANCOVA test of treatment group effect: F=2.1, p=0.15; effect size for risperidone vs olanzapine= −0.51

Subjective feelings (% change estimated from Figure 2): risperidone= +9.5% vs olanzapine= +20% vs first-generation agents= +7.5% vs combined therapy= −2%; 2-way ANCOVA test of treatment group effect: F=2.7, p=0.050; effect size for risperidone vs olanzapine= −0.29

Leisure time activities (% change estimated from Figure 2): risperidone= +13% vs olanzapine= +20.5% vs first-generation agents= +4% vs combined therapy= −2%; 2-way ANCOVA test of treatment group effect: F=3.2, p=0.026; effect size for risperidone vs olanzapine= −0.18

Social relationships (% change estimated from Figure 2): risperidone= +6% vs olanzapine= +14% vs first-generation agents= +8% vs combined therapy= +0.5%; 2-way ANCOVA test of treatment group effect: F=0.6, p=0.64; effect size for risperidone vs olanzapine= −0.28

General activity (% change estimated from Figure 2): risperidone= −3% vs olanzapine= +6% vs first-generation agents= +3.5% vs combined therapy= +4%; 2-way ANCOVA test of treatment group effect: F=0.3, p=0.84; effect size for risperidone vs olanzapine= −0.52

Life satisfaction (% change estimated from Figure 2): risperidone= +3.5% vs olanzapine= +26.5% vs first-generation agents= +22% vs combined therapy= +2%; 2-way ANCOVA test of treatment group effect: F=0.2, p=0.88; effect size for risperidone vs olanzapine= −0.42
NR
Sax, 1998
United States
University of Cincinnati Medical Center siteProspectiveNR6 weeksquetiapine 330mg
6 weeks
SchizophreniaMean age=32
70% male
80% Caucasian
NR/NR/10NR/NR/10Patients(n=10) vs Controls(n=12)
CPT sensitivity, mean (SD)
 initial: 0.82(0.10) vs 0.93(0.07), p<0.01
 first follow up: 0.88(0.08) vs NA
 second follow up: 0.92(0.07)* vs 0.94(0.08) (*p<0.01 vs baseline)

No significant correlations between changes in symptom scores and CPT performance results, or between dosage of quetiapine and CPT and BPRS changes over time.
NR
Schillevoort, 2001
Netherlands
PHARMO-databaseRetrospective90 daysNRhaloperidol: 2.2 mg/d, risperidone: 54 mg/d, olanzapine mg/dSchizophreniaMean age: 35.3 years
48.6% Male
Ethnicity NR
450,000/NR/8480/0/848NRUse of antiparkinsonian medication at baseline:
R: 36.2% vs O: 40.3% vs H: 4.5%; p<0.001No significant differences found at endpoint for use of antiparkinsonian medication with antipsychotic
Schillevoort, 2001b
Netherlands
PHARMO-databaseRetrospective90 daysNRMedian doses
risperidone: 2.0 mg/day
haloperidol: 2.2 mg/day
zuclopenthixol: 6.0 mg/day
perphenazine: 5.3 mg/day
thioridazine: 48 mg/day
pipamperone: 40 mg/day
chlorpromazine: 63 mg/day
SchizophreniaMean age: 36 years
45.9% Male
Ethnicity NR
450,000/4094/40940/0/4094NRCrude relative risk for anticholinergic medication (95% CI):
risperidone vs haloperidol: 0.44 (0.20, 1.01)
risperidone vs zuclopenthixol: 0.49 (0.21, 1.13)
risperidone vs perphenazine: 1.92 (0.74, 5.01)
risperidone vs thioridazine: 3.12 (1.21, 8.04)
risperidone vs pipamperone: 4.25 (1.54, 11.72)
risperidone vs chlorpromazine: 2.97 (0.35, 24.97)
Sernyak, 2002
United States
Veterans Health Administration of the Department of Veterans Affairs (VA)RetrospectiveOctober 1, 1999 to September 30 19994 monthsClozapine, olanzapine, risperidone, quetiapinePatients prescribed to study drugsMean age: 52.6 years
5.2% Female
African-American: 25%
Hispanic: 4.3%
NR/NR/38,632NR/NR/38,682Analysis of Association Between Atypicals vs Typicals: 95% CI; p-value
clozapine: 1.07–1.46; P<0.005
olanzapine: 1.04–1.18; P<0.002
quetiapine: 1.11–1.55; P<0.002
risperidone: 0.98–1.12; P=0.15
NR
Shajahan, 2009, ScotlandChart Review: Lanarkshire, ScotlandRetrospective2002–2007≤5 yearsAripiprazole (N=89): starting dose: 10.2 mg/day, max dose 18.7 mg/day; Quetiapine (N=132): starting dose 91 mg/day, max dose 422 mg/dayDiagnosed schizophrenia and related psychoses, onset of treatment with either drug after 2002, and more than one mental health contactMean age (Aripiprazole/Quetiapine): 39.6 years/36.7 years; % Male (Aripiprazole/Quetiapine): 58%/52%;
Ethnicity: NR
NR/22000/221NR
NR
221 (89 aripiprazole, 132 quetiapine)
Medication discontinuation rates (Aripiprazole/Quetiapine): 45%/42% ; Time to discontinuation (Aripiprazole/Quetiapine): 103 days/175 daysNR
Sharif, 2000
United States
Creedmoor Psychiatric Center, Columbia UniversityRetrospective12 weeks4 weeksClozapine: 520 mg/day
Risperidone: 7.5 mg/day
Schizophrenia, schizoaffective disorderMean age: 35.9 years
54% Male
White: 63%
Black: 21%
Hispanic: 13%
Asian: 4%
NR/NR/24NR/NR/24Patients classified as responders to treatment:
clozapine: 14(58%) vs risperidone: 6(25%)
Response rates:
Positive symptoms: clozapine: 38% vs risperidone: 17%
Negative symptoms: clozapine: 29% vs risperidone: 8%
Aggressive symptoms: clozapine: 71% vs risperidone: 41%
Response rates: Clinical Global Impressions-Improvement scores ≤2:
Global rating: R: 25% vs C: 58%
Positive symptoms: R: 17% vs C: 38%
Negative symptoms: R: 8% vs C: 29%
Aggressivity: R: 41% vs C: 71%
Snaterse, 2000
Canada
Alberta Hospital EdmontonRetrospective12 months12 monthsRisperidone(N=35): 4.17 mg/day
Olanzapine(N=21): 15.24 mg/day
Schizophrenia, schizoaffective disorderMean age: 38.8 years
40.5% Female
Ethnicity NR
NR/NR/56NR/NR/56Time to initial response:
R: 14.3 days vs O: 30.9 days; P<0.00001
Time to discharge:
R: 36.6 days vs 58.2 days; P=0.0201
Re-admission rate at 12 months:
R: 31.4% vs O: 61.9%; P=0.026
Soholm, 2003
Denmark
Patient records from the Psychiatric University Clinic, Rigshospitalet, Copenhagen University Hospital, DenmarkRetrospective>1997NR1st line of treatment: conventional antipsychotic or clozapine
2nd line of treatment: atypical antipsychotic
Schizophrenia, schizotypal disorder, or schizoaffective disorderMean age (years): 38.7
% male: 63
NR/71/57NR/NR/57Significantly more individuals were in the olanzapine group than in the risperidone group (P=0.0001)
Most common diagnosis of individuals was schizophrenia
67% of those treated with newer atypical antipsychotics as the first line of treatment, stayed on treatment for the duration
Those taking olanzapine had significantly fewer days in the hospital (P=0.001)
No significant differences were found between groups for adverse effects. The severity of extrapyramidal symptoms was generally reduced in all groups.
Soyka, 2005
Germany (inpatients)
Psychiatric Hospital of the University of Munich

Non-randomized, comparative
ProspectiveCurrent hospitalization time (weeks), risperidone vs haloperidol: 6.8 vs 6.2 weeksNRAverage dose /d
Risperidone: 4.6 mg/d
Haloperidol: 10.4 mg/d
Schizophrenia or schizoaffective disorderMean age: 32.95y
67.5% male
Ethnicity: NR
NR/ NR/ 59NR/ NR / 59Driving ability tests (all subjects had licenses), risperidone vs haloperidol vs control:
 Psychomotor test performance (no p-values given):
  passed: 35% vs 5% vs 85%
  low performance: 40% vs 35% vs 15%
  very low performance: 25% vs 60% vs 0%
Number of pts who failed in each test, risperidone vs haloperidol vs control:
 PVT (peripheral vision test with tracking task, incl. reaction time): 5 vs 13 vs 0
 TT15 (tachistoscope test, ability to quickly extract relevant info):1 vs 4 vs 0
 Q1 (attention test under a monotonous condition): 7 vs 11 vs 2
 RST3 (reactive stress tolerance test): 11 vs 16 vs 1

Mean BPRS at examination: risperidone=28 vs haloperidol=27.4 (p=NS)
NRTests are relevant to the German Road Traffic Safety Board.
Spivak, 1998
Israel
Naturalistic: Ness-Ziona Mental Health CenterProspective1 yearNRClozapine 295 mg
CAPD (chlorpromazine equivalent) 348.9 mg
Treatment resistant schizophreniaMean age=38.3
48.3% male
Race NR
NR
NR
60
NR
NR
60
NRSuicide
Attempts
0 vs 5 (16.7%); p<0.05
Strassnig, 2007
United States
Subset of data from larger ongoing trialUnclear1990–20061 yearClassic and novel antipsychoticsFirst-episode psychotic episodeSubjects/Controls
Mean age (years): 27.2/21.3
% male: 69.8/61.5
NR/NR/NRNR/NR/98 subjects
& 30 controls
Weight Changes
Patients on antipsychotics experienced significantly more weight gain during the 1-year observation period and their body mass index increased to a significantly greater extent than their healthy controls (P=0.002)
More weight gain was experienced by younger subjects (P=0.019)
Side-effect medications were prescribed more often for those taking haloperidol and perphenazine
Strous, 2006
Israel
Clinic visitsProspectiveNR12 weeksRisperidone, olanzapine, clozapineSchizophrenia or schizoaffective disordersMean age=36.7
58.0% male
Race NR
NR/NR/1310/0/131NRProportional increase in weight:
Clozapine=6.9%
Olanzapine=2.7%
Risperidone=2.1%
2x3x2 ANOVA results (gender and group as between-subjects and time as within subjects factors): F(2,128)=8.52, p<0.0001
Post-hoc Tukey-HSD 2x2 comparisons: Clozapine vs olanzapine (p<0.05) and vs risperidone (p<0.05)
Su, 2005
Taiwan
Clinic visitsProspectiveNR3 monthsOlanzapine 7.9mg, risperidone 2.5mgDSM-IV criteria for schizophrenia; poor or partial response to current antipsychotic (olanzapine or risperidone) for at least 3 monthsMean age=35.7
53% male
Ethnicity NR
NR/30/15NR/NR/15NRChange in Mean Body Weight in kg: Baseline/endpoint (% change)
Olanzapine (after switch from risperidone): 70.1/66.1 (−6%), p=0.049
Risperidone (after switch from olanzapine): 65.9/69.9 (+6%), p=0.008

Change in BMI: Baseline/endpoint (% change)
Olanzapine (after switch from risperidone): 25.7/24.2 (−6%), p=0.04
Risperidone (after switch from olanzapine): 24.8/25.9 (+4%), p=NS
Sumiyoshi, 2004
United States
Outpatient community mental health center (Mental Health
Cooperative at Nashville, TN)
Prospective (with retrospective epidemiologic survey of clinical and demographic information)February 2001 to May 2002NRClozapine, Risperidone, Olanzapine or QuetiapinePatients who visited the mental health center during the sampling frame and if he or she was receiving clozapine, risperidone, olanzapine or quetiapine

46.6% diagnosed with schizophrenia spectrum disorders
Mean age (SD): 42.9 (10.6) years
56.9% male
60.3% white; 39.7% non-white
NR/NR/116NR/NR/116NRNonparametric survival analysis indicated no statistically signifcant difference in time to onset of type 1 and type 2 diabetes mellitus between clozapine (median: 112 days; mean (SD): 495.6 (738.4) days), risperidone (median: 502 days; mean (SD): 789.8 (829.9) days), and olanzapine (median: 399 days; mean (SD): 602.8 (574) days). P=0.43
Swanson, 2004
United States
Medical records from the North
Carolina site of the Schizophrenia
Care and Assessment Program
Retrospective1997 to 19993 yearsOlanzapine
Risperidone
Schizophrenia-related disordersMean age (years): 46.1
% male: 56
% African-American: 67.7
NR/NR/124NR/NR/124Olanzapine takers had a reduced probability of violence over time
Trend toward greater compliance with medication among those who remained on olanzapine therapy for ≥ 12 months (OR=1.94, p=0.07)
NR
Taylor, 2003
UK
U.K. Risperidone Olanzapine
Drug Outcomes Studies in Schizophrenia program (RODOS-UK)
Retrospective4 monthsNRrisperidone: 5.5±2.4 mg/day
olanzapine: 14.1±4.7 mg/day
Schizophrenia, schizoaffective disorderMean age: 36.2 years
68.5% male
Ethnicity NR
NR/NR/501NR/NR/499% of effectiveness:
R: 78% vs O: 74%; P=.39
Mean time to onset of effectiveness:
R: 17.6 days vs O: 22.4 days; P=.01
Mean days in hospitalization:
R: 58 days vs R: 49 days; P=.007
% of patients discontinued due to side effects:
R: 3.7% vs O: 2.3%
Events reported: body as a whole, central/peripheral nervous system, psychiatric, gastrointestinal, metabolic/nutritional, heart rate/rhythms
Taylor, 2006
UK-Scotland
Not reportedProspective2002 plus 6 month follow-up6 monthsAt 6 months mean doses were amisulpride (n=16) 487.5mg, for clozapine (n=12) 429 mg, for olanzapine (n=65) 13.7 mg, for quetiapine (n=8) 350 mg, and for risperidone (n=56) 3.4 mg.All patients from adolescent, adult, and old age psychiatry in the Greater Glasgow area (population -1.0 million) with a clinical diagnosis (from a senior psychiatrist) of schizophrenia or schizophreniform disorder.Mean age 45.9 years
51% male
Ethnicity-NR
NR study started with 373 patients81/NR/101Mean change from baseline and % change
CGI Amisulpride 0.85 19% Clozapine 1.80 34% Olanzapine 1.18 33% Quetiapine 0.83 11%
Positive symps Amisulpride 0.55 30% Clozapine1.50 54% Olanzapine 0.9 51% Quetiapine 0.67 26%
Negative symps Amisulpride 0.40 24% Clozapine 0.40 20% Olanzapine 0.26 11% Quetiapine 1.00 39%
Side effects, Amisulpride 0.87 54% (1.5) Clozapine 0.10 13% Olanzapine 0.90 51% Quetiapine 1.50 53%
Quality of life, Amisulpride 0.38 15% Clozapine 1.10 34% (1.7)Olanzapine 0.96 36% Quetiapine 1.17 31%
NR
Taylor, 2008, ScotlandCase record review: Lankshire, ScotlandRetrospectiveFebruary 2002–June 2005NRMean Dose for Schizophrenia (Amisulpride/Olanzapine/Quetiapine/Risperidone/Clozapine): 589/15.5/441/6.0/427 mg/dSchizophrenia or related psychoses (aged 16–65), and initiation of treatment with SGAs after EPR reviews commencedMean age
(Amisulpride/Olanzapine/Quetiapine/Risperidone/Clozapine): 41/40/41/43/37 years; % Male
(Amisulpride/Olanzapine/Quetiapine/Risperidone/Clozapine): 63/64/38/62/65%; Ethnicity: NR
NR
11250
1464
NR
NR
1464
Medication discontinuation rates (Amisulpride/Olanzapine/Quetiapine/Risperidone/Clozapine):
51/41/36/28/18%; Adjusted discontinuation rates
(Amisulpride/Olanzapine/Quetiapine/Risperidone/Clozapine): 0.71/0.64/0.54/0.53/0.25; Medication discontinuation rate due to side effects (Amisulpride/Olanzapine/Quetiapine/Risperidone/Clozapine): 35/32/46/0/14%; Medication discontinuation rate due to inefficacy
(Amisulpride/Olanzapine/Quetiapine/Risperidone/Clozapine): 33/28/36/73/0%; Medication discontinuation rate due to ‘other’ (Amisulpride/Olanzapine/Quetiapine/Risperidone/Clozapine):
32/40/18/27/86%; Mean number of days to discontinuation
(Amisulpride/Olanzapine/Quetiapine/Risperidone/Clozapine): 232/256/191/152/427 days
NRMax doses were not reported but results were discussed
Tiihonen, 2006
Finland
Community careProspective1996–20013.6 yearsOlanzapine, clozapine, risperidone, oral perphenazine, thioridazine, perphenazine depot, chlorprothixene, chlorpromazine, haloperidol, and levomepromazineAll people in Finland who were hospitalized because of a diagnosis of schizophrenia or schizoaffective disorder; index ages 15–45 yearsMean age 30.7 years
62% male
Ethnicity or race NR
NA-all were included that were hospitalized in Finland0/0/2230Hospitalization-Drug and crude RR/adjusted RR (sex, calendar year, age at onset of follow-up, number of previous relapses, duration of index hospitalization, and length of follow-up)
Perphenazine depot 0.54 (0.41 to 0.70) 0.54 (0.41 to 0.70)
Clozapine 0.79 (0.66 to 0.95) 0.64 (0.53 to 0.77)
Olanzapine 0.81 (0.67 to 0.97) 0.67 (0.56 to 0.80)
Thioridazine 0.73 (0.59 to 0.91) 0.75 (0.60 to 0.93)
Perphenazine oral 0.66 (0.54 to 0.80) 0.77 (0.63 to 0.94)
Chlorpromazine 0.83 (0.66 to 1.04) 0.89 (0.71 to 1.12)
Chlorprothixene 0.85 (0.68 to 1.06) 0.90 (0.72 to 1.13)
Mixed or rare 1.05 (0.89 to 1.25) 0.91 (0.76 to 1.08)
Haloperidol oral 1.00 1.00
Levomepromazine 1.53 (1.22 to 1.93) 1.01 (0.80 to 1.27)
Risperidone 0.89 (0.74 to 1.06) 0.87 (0.73 to 1.05)
84 patients died during follow-up, no significant differences between drugs but, mortality was more than 10 times higher in patients not taking drugs than in patients currently taking antipsychotic drugs: 75 patients not taking drugs died (3362 person years) and nine patients taking drugs
died (4664 person years) (adjusted relative risk 12.3) Twenty six suicides occurred in patients not taking drugs compared with one suicide in patients taking drugs (crude relative risk 36.1, 4.9–266)
Tiihonen, 2009
Finland
National Hospital Discharge RegisterRetrospectiveJanuary 1, 1996 to 2006 (because prescription data are available only after 1995)11-year follow-up with average of 8.6 yearsFirst generation and second generation antipsychotic drugs either as monotherapy or combinations, as well as no therapyAll patients in Finland who were admitted with a diagnosis of schizophrenia from Jan 1, 1973, to Dec 31, 2004Mean age: 51 years
46.1% male
NA: all patients in Finland admitted with a diagnosis of schizophreniaNA/NA/66881NROverall risk of death was lower during the current use of any antipsychotic drug than it was with no antipsychotic use; adjusted HR, 0.68; 95% CI, 0.65 to 0.71; P<0.0001).
Risk of death significantly lower in patients with long term (7–11 years) antipsychotic treatment than in those who had not used any antipsychotic drugs during follow-up; HR, 0.81; 95% CI, 0.77 to 0.84; P<0.0001)
Life expentancy of patients with schizohrenia had not declined during the study period compared with the general population (32.5 years vs 57.5 years in 1996 respectively; 37.4 years vs 59.9 years in 2006 respectively)
Usall, 2009 SOHO (Secondary publication) Reporting on gender differences in SchizophreniaSame as Haro 2005Same as Haro 20056 month analysisNRMale vs female
Olanzapine: 11.08 (5.37) vs 10.19 (4.99)
Risperidone: 4.67 (2.57) vs 4.09 (2.54)
Clozapine: 159.68 (125.03) vs 148.01 (125.63)
Schizophreniaage: 39.7
% male: 56.7
Ethnicity: NR
NR/NR/7990NR/NR/7990Overall CGI response
Odds ratio for gender [Female reference category], 95% CI, p-value
Olanzapine: 0.88 (0.78 to 1.00), p=0.0460
Risperidone: 0.90 (0.74 to 1.10), p=0.2969
Clozapine: 0.56 (0.34 to 0.93), p=0.0252
Typical cohort: 0.62 (0.48 to 0.82), p=0.0006

EQ-VAS change from baseline, differences in rating by gender (female reference category)
Olanzapine: −1.52(−2.53 to −0.50), p=0.0033
Risperidone: 0.27 (−1.28 to 1.83), p=0.7300
Clozapine: −2.03 (−6.06 to 2.00), p=0.3243
Typical cohort: −2.16 (−4.33 to 0.01), p=0.0505
van Winkel, 2008, BelgiumUniversity Psychiatric Center of the Katholieke Universiteit Leuven in Kortenberg, BelgiumProspectiveNovember 2003–January 20073 monthsNRPatients with schizophrenia or schizoaffective disorder, newly started on or switched to specific atypical antipsychotic medication therapy, with OGTT-confirmed non-diabetic statusMean age: 33.7 years; % Male: 60.7%; Ethnicity: NRNR/415/183NRNR8 patients developed diabetes within 3 months after the start of the atypical antipsychotic, resulting in a 3-month incidence rate of 4.4%.
Initiation of clozapine
9.5% of patients initiated on clozapine, 8.0% of patients initiated on olanzapine, 4.2% of patients initiated on quetiapine, and 2.1% of patients initiated on risperidone developed new-onset diabetes, whereas no new cases developed in patients initiated on aripiprazole and amisulpride.
5 of the 8 (62.5%) had prediabetic abnormalities at baseline; 3 (37.5%) had no glucose abnormalities.
Type of initiation (start or switch) did not affect the metabolic parameters.

BMI (kg/m2)at baseline and after 3 months:
amisulpride = 26.5, 27.9
aripiprazole = 28.4, 27.3
clozapine = 24.8, 26.5
olanzapine = 23.5, 25.8
quetiapine = 25.2, 26.8
risperidone = 24.9, 25.8
Sample size (183) was small for assessing the low incidence rates typically reported for diabetes. Study was naturalistic: there was no random allocation of antipsychotic medication which resulted in treatment cohorts of different sizes.
Verma, 2001
United States
Houston VA Medical CenterRetrospectiveAverage: 25 daysNRrisperidone: 2.2 mg
olanzapine: 13.2 mg
SchizophreniaMean age: 71.4 years
100% male
71% Caucasian, 23% African-American, 6% Hispanic
NR/NR/NRNR/NR/34Changes in scores at discharge:
Positive and negative symptoms (PANSS): R: 56.90 vs O: 59.0; P=0.735
Extrapyramidal side-effect rating scale (ESRS): R: 23.46 vs O: 20.54; P=0.557
Rating scale for side effects (RRSE): R: 8.14 vs O: 7.71; P=0.817
NR
Voruganti, 2000
Voruganti, 2002
Canada
Western Ontario schizophrenia research programRetrospectiveNR≥6 monthsRisperidone(N=50): 2–8 mg
Olanzapine(N=50): 15–40 mg
Quetiapine(N=50): 200–800 mg
Switched from following conventional drugs (CAPD): chlorpromazine, fluphenazine, flupenthixol, haloperidol, methotrimeprazine, perphenazine, pimozide, Pipothiazine, trifluoperazine
SchizophreniaMean age: 32.1 years
68.7% male
NR/230/15015 withdrawals or lose to follow up/13585% of patients benefitted from switching from conventional to novel antipsychotics
8(6%) preferred conventional treatment
Remained on maintenance treatment:
risperidone 82%
olanzapine 86%
quetiapine 82%

CAPD (n=44) vs risperidone (n=50) vs olanzapine (n=48) vs quetiapine (n=42) vs clozapine (n=46)
Psychosocial functioning and quality of life:
 Sickness impact profile (SIP): 35.3(13.2)* vs 26.9(14.3) vs 29.1(14.8) vs 28.2(10.6) vs 32.1(18.1)
 Quality of life (QLS): 58.8(22.6) vs 63.3(15.3) vs 60.8(15.4) vs 61.4(14.2) vs 58.2(14.8)
 Global assessment of functioning scale (GAF): 59.8(14.5) vs 61.9(10.5) vs 59.4(8.9) vs 56.8(12.6) vs 57.8(10.6) (*p<0.05 on Tukey tests)

Mean change in scores after a switch from conventional to the novel antipsychotic drugs
risperidone (n=43) vs olanzapine (n=44) vs quetiapine (n=31)
Symptoms
 1. PANSS: −23.63 vs −23.67 vs −21.43
  a. positive symptoms cluster: −5.18 vs −4.11 vs −4.67
  b. negative symptoms cluster: −8.2* vs −6.3 vs −5.0
  c. excited symptoms cluster: −3.68 vs 2.79 vs −1.03
  d. depressive symptoms cluster: 2.68 vs −6.09* vs −1.70
  e. cognitive symptoms cluster: −3.89 vs −4.38 vs −9.03*
Quality of life
 1. QLS: 10.30 vs 9.97 vs 9.87
 2. GAF: 16.0 vs 15.18 vs 14.67
 3. SIP: −22.32 vs −20.40 vs −21.20 (*p<0.05 on post hoc Tukey tests)
CAPD (n=44) vs risperidone (n=50) vs olanzapine (n=48) vs quetiapine (n=42) vs clozapine (n=46)
Drug attitude inventory scores:
 1. DAI-30 total: 12.9(10.5) vs 19.4(9.1)* vs 18.9(8.9)* vs 18.2(10.2)* vs 16.2(11.0)
 2. subjective positive: 3.1(4.2) vs 5.4(3.3)* vs 5.5(2.7)* vs 5.8(3.8)* vs 4.9(3.6)
 3. subjective negative: 2.4(3.5) vs 3.2(2.8) vs 3.5(2.5) vs 2.7(3.2) vs 2.4(3.3)
 4. health/illness: 1.7(1.1) vs 1.7(1.8) vs 1.6(1.6) vs 1.5(1.2) vs 1.2(1.9)
 5. professionals: 1.6(0.9) vs 1.7(0.7) vs 1.1(1.5) vs 1.6(0.9) vs 1.5(1.0)
 6. control issues: 0.6(1.3) vs 1.4(1.1) vs 1.3(1.2) vs 0.9(1.2) vs 1.2(1.2)
 7. prevention: 1.1(1.0) vs 1.6(0.9) vs 1.3(1.2) vs 1.5(1.1) vs 1.4(1.7)
 8. harmful effects: 0.4(1.3) vs 0.9(1.3) vs 0.9(1.2) vs 0.8(1.0) vs 0.6(1.5)
Proportion of dysphoric responders:7(17%)* vs 3(6%) vs 2(5%) vs 3(7%) vs 3(6.5%)
Severity of side effects
 1. Simpson-Angus EPS rating scale: 3.4(2.3)* vs 1.34(2.4) vs 0.9(2.0) vs 1.1(2.2) vs 0.4(1.4)
 2. BAS: 1.2(1.4) vs 0.8(0.9) vs 0.2(0.6) vs 1(1.2) vs 0.6(1.0)
 3. AIMS: 1.6(2.1) vs 1.2(2.4) vs 1.4(2.8) vs 1.2(3.2) vs 3.5(5.8)
 4. LUNSERS: 21.1(9.6)* vs 13.4(9.4) vs 13.4(4.0) vs 12.8(7.2) vs 25.4(15.7)* (*p<0.05 on Tukey tests)
Mean change in scores after a switch from conventional to the novel antipsychotic drugs risperidone (n=43) vs olanzapine (n=44) vs quetiapine (n=31)
Side effects
 1. AIMS: −0.21 vs −0.75 vs −0.12
 2. BAS: 3.40 vs −4.52 vs −3.96
 3. SAS: −6.02 vs −6.75 vs −6.67
 4. LUNSERS: −21.86 vs −23.18 vs −30.7*
Subjective tolerability:
 1. DAI: 11.86 vs 14.6* vs 12.12
 2. proportion of dysphoric responders in the group (%):−6.9 vs −13.6 vs −9.7 (*p<0.05 on post hoc Tukey tests)
Wang, 2002
U.S.
Databases: NJ Medicaid program & NJ Pharmaceutical Assistance to the Aged & Disabled program plus MedicareRetrospective6 months before date of 1st prescription for insulin or oral hypoglycemic agent6 monthsclozapine vs other psychiatric agents (includes typical APs and risperidone);
Dose and duration of treatment during the 6-month observation period were included in the analysis
Patients with psychiatric disorders, age>20, enrolled in government-sponsored drug benefit programs in New Jersey. Cases were patients with a 1st prescription (index date) for insulin or oral hypoglycemics between 1990–1995. Controls were patients without diabetes, matched on age, gender, and a randomly assigned index date. Subjects were then selected for analysis if they had a psychiatric diagnosis in the previous 6 months.Mean age 62.5
31.8% male
64% white
NR
NR
14007
NR
NR
14007 analyzed
Cases with diabetes mellitus n=7227
Controls without diabetes mellitus n=6780
NRAdjusted odds of diabetes mellitus associated with clozapine use: 0.98 (95% CI 0.74–1.31)
Adjusted odds of DM associated with use of other antipsychotics: 1.13 (95% CI 1.05–1.22)
Adjusted odds of DM associated with specific antipsychotics (95% CI):
risperidone 0.90 (0.96–1.18)
chlorpromazine 1.31 (1.09–1.56)
perphenazine 1.34 (1.11–1.62)
haloperidol 1.06 (0.96–1.18)
Duration of treatment and previous treatment with clozapine, prior to the 6-month window of observation were not included in the analysis.
Weiser, 2000
Israel
Tel-Aviv University Medical SchoolRetrospectiveNRNRHaloperidol(N=23): 10 mg/day
Olanzapine(N=26): 10.56 mg/day
Risperidone(N=27): 4.35 mg/day
Schizophrenia, schizophreniform disorderMean age: 30.9 years
68% Male
Ethnicity NR
NR/NR/NRNR/NR/76Cognitive functioning as measured by VMT:
Higher for olanzapine and risperidone vs haloperidol: P=0.002
CPT scores: R: 0.541 vs O: 0.516 vs H: 0.300; F=1.003
Calgary Depression Scale: R: 6.73 vs O: 4.53 vs H: 7.75; F=1.974
Rey VLT: R: 38.0 vs O: 40.3 vs H: 36.0; F=0.674
PANSS: R: 66.8 vs O: 63.3 vs 68.2; F=0.568
Haloperidol and risperidone suffered more severe EPS vs olanzapine: P=0.023
Wirshing, 2002
United States
VA Greater Los Angeles Healthcare SystemRetrospectiveMean duration:
clozapine: 43.3 mo
olanzapine: 13.5 mo
risperidone: 28.6 mo
quetiapine: 33.o mo
haloperidol: 37.1 mo
fluphenazine: 47.0 mo
NRClozapine, olanzapine, risperidone, quetiapine, haloperidol, fluphenazine/mean doses NRSchizophreniaMean age: 51.3 years
94.4% Male
47.9% White
36.7% African-American
NR/590/2150/0/215NRIncrease in glucose levels from baseline:
clozapine: +14%; p=.05
olanzapine: +21%; p=.03
haloperidol: +7%; p=.04
Increase/decrease in total cholesterol levels from baseline:
risperidone: −6%, p=.04
fluphenazine: −6%; p=.04
13% of olanzapine patients (4) required increases in doses of lipid-lowering agents after beginning treatment
Yood, 2009
U.S.A.
3 sites: Kaiser Permanente Health Plan, Northern California;
HealthCore Integrated Research Network;
PharMetrics
RetrospectiveNov 2002 through March 2005minimum 45 days% of inception cohort (N=56,037)
Aripiprazole 4.5%
Clozapine 0.1%
Olanzapine 22.2%
Quetiapine 18.2%
Risperidone 19.6%
Ziprasidone 2.9%
Typical antipsychotics 10.5%
Mean dose NR
Inception cohort subset: all patients aged 18 and older exposed to typical or atypical antipsychotics for at least 45 days and continuously enrolled in the database for at least 3 months before and 6 months after the index date with no evidence of diabetes anytime before the index date, and no previous antipsychotic prescription filled within 3 months before the index date.Mean (SD) age: 45.1 (19.4)
39.7% male
Ethnicity NR
77946 = simple cohort 56037 eligible as inception cohort All eligible were included in analysis.No withdrawals, no loss to followup: subjects selected based on continuous enrollment for 6 months after index date.
56,037 analyzed.
NROlanzapine and clozapine were associated with increased risk of diabetes. Aripiprazole, ziprasidone, risperidone, and quetiapine did not show an increased risk. HR (95% CI) for incident diabetes adjusted for sex, study site, history of AP use, exposure to other pharmacotherapy, overweight, schizophrenia and bipolar disorder code: (Typical antipsychotic = referent)
Aripiprazole: 0.93 (0.50, 1.76)
Clozapine: 2.58 (0.76, 8.80); p=0.13 (based on 3 events in 147 exposed patients)
Olanzapine: 1.71 (1.12, 2.61); p=0.01 (based on 139 events in 17119 exposed patients)
Quetiapine: 1.04 (0.67, 1.62)
Risperidone: 0.85 (0.54, 1.36)
Ziprasidone: 1.05 (0.54, 2.08)
Multiple: 1.29 (0.64, 2.62)
The effect estimate for clozapine is imprecise due to the small N's
Yu, 2008
U.S.A.
Pennsylvania Medicaid claims data.Retrospective4 years: 1999–200312 months after index prescription.Olanzapine (N=6929) or quetiapine (n=2321) monotherapy for 30 days or longer, classified based on the initial atypical antipsychotic received during the observation period, regardless of switching pattern. Dose NR.Adult schizophrenia patients aged 18–64 who were continuously enrolled at least 1 year before and 1 year after the index prescription date, received a do-day monotherapy of either olanzapine or quetiapine after a 90-day washout period during June 2000 to June 2002. Excluded patients who had a managed care organization claim on or after the index prescription date.Quetiapine (N=2321) vs. olanzapine (6929)//olanzapine cohort (N=2321) matched on propensity score:
Mean age: 41.3 vs 42.8//41.6
% male: 39.9% vs 52.8%//40.2%
% White: 65.5% vs 55.2%//64.3%
% Black: 28.3% vs 36.7%//29.1%
% Hispanic: 2.0% vs 3.2%//1.9%
Exposed: 22167 had a pharmacy claim for either drug within index window (2000–2002)
Eligible: 9250 met all criteria
Selected: all eligible were included
No withdrawals, no loss to followup: subjects selected based on continuous enrollment for 12 months 4642 analyzed.Compared with quetiapine, patients treated with olanzapine had significantly fewer psychiatric hospitalizations, lower pharmacy utilization, and lower medical service costs.
Olanzapine (N=2321) vs quetiapine (N=2321):
% any psychiatric hospitalization: 28.8% vs 34.0%; p=0.0001
% any emergency visit: 47.0% vs 52.0%: p=0.0007
Any use of clozapine: 4.6% vs 7.1%; p=0.0003
Any use of antidepressants: 65.0% vs 71.3%; p<0.0001
Any use of mood stabilizers: 51.9% vs 57.9%; p<0.0001
Any use of benzodiazepines/hyptnotics/anxiolytics: 47.6% vs 52.1%; p=0.0020
Mean (SD) psychiatric costs, $: 7352 (14,282) vs 9037 (16,904); p=0.0002
Mean (SD) psychiatric hospitalization costs, $: 3149 (10,638) vs 4220 (13,838); p=0.0024
Mean (SD) psychotropic drug costs excluding index drug, $: 1828 (2131) vs 2459 (2477); p<0.0001
Total mean (SD) costs: 16,028 (19,182) vs 17,232 (19,162); p=0.0279

Reduction in costs (postindex minus preindex), adjusted for baseline characteristics:
Medical service cost: $2106 vs $869 p=0.0046
Psychiatric cost: $2017 vs $587; p=0.0004
Psychiatirc hospitalization cost: $1566 vs $574; p=0.0043
Drug cost: $3578 vs $3304; p=0.0059
Psychotropic drug cost: $3097 vs $2736; p<0.0001
Total costs: $1473 vs $2435; p=0.0320
Use of antiparkinsonian medication during 12-month postindex period was slightly but significantly lower with olanzapine vs quetiapine: 25.9% vs 28.9%; p=0.0214
Zhang, 2007, ChinaRandomly recruited inpatients from Beijing Hui-Long-Guan Hospital, Beijing City, ChinaBoth? (cross- sectional)NR7.5 ± 6.5 yearsMean dose (in chlorpromazine equivalents): 419 ± 337.6 mg/dayChronic schizophrenic patients (chronically treated with clozapine, risperidone or typical antipsychotics) and healthy control subjectsSubjects/Controls
Mean age (years): 47.3/46.2
% male: 73.4/72%
Ethnicity: 100% Han Chinese for both subjects and controls
NR/NR/124patient s and 50 controlsWithdrawn: NR
Lost to FU: NR
Analyzed:
124 schizophrenic patients (clozapine n=57, risperidone n=23, typical antipsychotics n=44)
50 healthy controls
NABMI values: subjects (male/female):
23.9 ± 3.5/25.8 ± 3.6
BMI values: controls (male/female):
21.5 ± 1.9/22.4 ± 2.1
BMI values when matched for BMI on a 1:1 basis: subjects (male/female):
21.5 ± 1.9/22.5 ± 1.9
BMI values when matched for BMI on a 1:1 basis: controls (male/female):
21.2 ± 1.8/22.4 ± 2.0

BMI/BMI gain (kg/m2)by drug class:
Typical: 23.7 ± 3.2/2.5 ± 3.1
Clozapine: 25.4 ± 3.4/3.9 ± 3.2
Risperidone: 22.9 ± 4.1/1.5 ± 3.7
Limited number of female patients
Zhao, 2002
United States
IMS Health Lifelink: Integrated Claims SolutionsRetrospectiveAverage: 181–217 daysNRrisperidone(N=985): 4.02 mg
olanzapine(N=348): 10.49 mg
SchizophreniaMean age: 48.6 years
53.5% male
Ethnicity NR
NR/NR/13330/0/1333Average days of treatment:
O: 217 vs R: 181; P<.0001
NR
Zhao, 2002
United States
Database: IMS Health Life Link: Integrated Claims SolutionsRetrospectiveOctober 1, 1996 through December 31, 19981 yearOlanzapine= 10.45mg/day
Risperidone= 3.32mg/day
SchizophreniaOlanzapine/Risperidone:
Mean age (years)=48.9/52.4
% female=44.4/52.2
745/670/670NR/NR/670Duration of treatment:
Olanzapine= 213 days
Risperidone= 162 days
After controlling for patient demographics, patients initiated on olanzapine stayed on therapy 29.4% longer than those initiated on risperidone (P<0.0001)
# of patients with >80% of days of receiving medication of interest:
Olanzapine= 176 of 423 (41.6%)
Risperidone= 64 of 247 (25.9%)
Incidence of switching:
Patients in olanzapine group were significantly less likely to switch to risperidone than vice versa (OR=0.275, P<0.0001, 95% CI 0.43–0.95)
Use of concomitant medications:
Olanzapine group significantly less likely to be prescribed an anti-Parkinsonian medication than risperidone group (OR=0.639, P=0.03, 95% CI 0.43–0.95) and had fewer treatment days with such medications (27.4% fewer days, P<0.0001)
NR
Uncontrolled studies
Alvarez, 1997
Spain
Naturalistic: Psychiatry Dept of the Hospital de Sant Pau since 1984 (Spain)Prospective6.7 years (mean)NRClozapine 266.9 mg (mean)Treatment resistant Schizophrenia/schizoaffectiveMean age=31.1
62.5% male
NR
NR
80
NR
NR
Unclear
Number of hospitalizations: before=2.65, after=0.35Weight increase (patients): 11 (13%)
Seizures (patients): 3 (3%)
Serious hematological side-effects: None
Responders vs Nonresponders
Atkin, 1996
UK/Ireland
Database: Clozaril Patient Monitoring System (CPMS)Retrospective1/7/90 to 7/3/94NRClozapine 313 mgTreatment resistant schizophreniaMean age=37
66.1% male
89% White
5% African/Afro-Caribbean
3.6% Asian
0.4% Oriental
1.9% Mixed
NR
NR
6316
NR
NR
Year1=6316
Year2=2858
Year3=1625
Year4=661
NRAgranulocytosis
Year1=46/6316(0.7%)
Year2=2/2858(0.07%)
Year3=0/1625
Year4=0/661
Fatal cases
Year1=2/6316 (0.03%)
Years2–4=0
Buckman, 1999
United States
Database: Illinois Dept of Mental Health and Developmental DisabilityUnclear1990 to 1995NRClozapineTreatment resistant schizophreniaNR
NR
NR
NR
951
518
NR
NR
518
NRAgranulocytosis Incidence=0.9%
Bunker, 1996
United States
Clozapine patient monitoring systemProspectiveFebruary 1990 to January 19963 yearsclozapine for 643 days44.4% paranoid
31.1% undifferentiated
0.02% catatonic
22.2% schizoaffective
Mean age=41.7 years
44.4% male
57.8% Caucasian; 42.2% African American
NR/NR/45NR/NR/45NR7/25 had emergent DE, average time to onset: 238±179 days, average time to resolution of DE symptoms: 347±190 days
baseline vs emergent DE- time to resolution: 261±188 vs 347±190, p<0.05
27 patients had a baseline or emergent DE
15/27(56%) had resolution of DE
10/27(37%) had complete resolution of DE
Conley, 1997
United States
Spring Grove Hospital CenterProspective1990–199512 monthsclozapine 468 mg/day
12 months
46.7% schizophrenia
34.7% schizoaffective disorder
10.7% bipolar disorder
8% atypical psychosis
Mean age=35.7 years
60% male
Ethnicity: NR
NR/NR/50NR/NR/50BPRS total scores: fall 31% from baseline, p<0.0001
BPRS 5 factor scores: fall 32% from baseline, p<0.0001
 anergia: fall 24%, p<0.01
 anxiety-depression: fall 30%, p<0.0001
 activation: fall 31%, p,0.0001
 hostility0suspiciousness: fall 46%, p<0.0001
11(33%) patients took longer than 8 weeks to initial respond
16(32%) never achieved clinical response
Responders vs non-responders:
Age: 33.79 vs 39.88, p<0.05
Years of hospitalization: 2.57 vs 7.2, p<0.05
BRPS
 Total score: 48.38 vs 44.25, NS
 Anxiety-depression factor: 9.97 vs 7.5, p<0.05
 Anergia factor: 7.29 vs 6.44, NS
 Thought disturbance factor: 10.71 vs 11.63, NS
 Activation factor: 6.91 vs 7.44, NS
 Hostility-suspiciousness factor: 9.35 vs 7.63, p<0.05
1 cardiovascular side effect
De Hert, 2008, BelgiumRecords and patients from University Psychiatric Centre Catholic University LeuvenRetrospective (including a subsample of prospective data for matched group)NRHistoric cohort: 1984–1995 (FGAs)
Current cohort: 2000–2005 (SGAs) (At least 1 year treatment exposure; average 3 years treatment exposure)
NRFirst-episode patients with schizophrenia treated with FGAs matched with first- episode schizophrenia patients treated with SGAs

Historic cohort was derived from a cohort of schizophrenic patients admitted between 1973 and 1992
Historic cohort/Current cohort:

Age: 22.3±3.2/22.1±3.1
Gender (% male): 65.5/71.6
Ethnicity: both cohorts were > 95% Caucasian and of native Belgian origin
Historic cohort:
1119
301
148

Current cohort:
NR
NR
148
NR
NR
296 (148 in historic cohort, matched with 148 in current cohort)
N/AMetS per antipsychotic in the SGA group (Baseline/Follow-up) (%):
Amisulpride: 12.5/25
Aripiprazole: 10/10
Clozapine: 8.3/58.3
Olanzapine: 5.8/47.1
Risperidone: 4.1/16.7
Quetiapine: 4.8/15

Mortality:
Historic cohort: 5% died (4.3% suicides, 0.7% cardiovascular)
Current cohort: 0% died

Historic cohort (data available on 130 patients up-to-date): 6 deaths (5 suicide, 1 cancer) Two deaths while still on an FGA and 6 when treated with an SGA later in the course of illness (4 on clozapine, of which 2 with ketoacidosis; 1 on olanzapine, and 1 on risperidone)
Deliliers, 2000
Italy
Database: Italian Clozapine Monitoring System (ICLOS)Unclear1995 to 1999NRClozapine 200–350 mgTreatment resistant schizophreniaMean age NR
63% male
Race NR
NR
NR
2404
NR
NR
2404
NRAgranulocytosis
16 cases (0.7%)
Devinsky, 1991
United States
Chart reviewUnclear1972 to 1988NRClozapineTreatment-resistant schizophreniaNR
NR
NR
1418
1418
1418
NR
NR
1418
NRSeizures
# cases=41/1418 (2.9%)
Dossenbach, 2000
Israel
5 study centersProspectiveNR18 weeksolanzapine 5–25 mg/day
18 weeks
chronic schizophreniaNR50/NR/485/3/48PANSS total score- baseline, mean reduced points, %: 115.3, 17.7, 14.2%
BPRS total score- baseline, mean reduced points, %: 44, 9.8, 20.2% (week 6 to week 18 show significant reduced points, p<0.001)
Responders- >=20% decrease
 PANSS: 18(40%)
 BPRS: 25(55.6%)
Responders- 30%, 40% decrease
 PANSS: 11(24.4%), 2(4.4%)
 BPRS: 17(37.8%), 13(28.9%)
CGI- achieved some degree of improvement: 24(53.3%)
Patient Global Impression- improvement: 23(51%)
24(50%) reported >= 1 treatment-emergent adverse event
SAS score- baseline vs week 6 vs week 18: 2.7 (vs 1.8 vs 1.6), p<0.001
AIMS score- baseline vs week 6 vs week 18: 2.6 (vs 1.5 vs 1.3), p<0.05
BAS score: NS
weight gain: 1.2±4 kg, p=NR
Drew, 2002
Australia
Database: Clozaril Patient Monitoring System (CPMS)Retrospective5 yearsNRClozapineSchizophrenia/schizoaffectiveNR
NR
NR
NR
42
32
NR
NR
32
NRAgranulocytosis: # cases=1/32 (3.1%)

Hospitalization(% pts admitted ≥ 1 day)
Pre-clozapine
2nd year=56.3%
1st year=59.4%
Post-clozapine
Year1=81.3%
Year2=31.3%
Year3=21.9%
Year4=18.8%
Year5=18.8%
Clozapine-naïve; commenced
Clozapine in Australian Capital
Territory (ACT) before 7/1/94
Eberhard, 2006
Sweden
MulticenterProspectiveNR5 yearsRisperidoneIndividuals treated with risperidone for at least 2 weeksMean age (years): 38.5NR/223/223NR/57/166Subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder had significantly higher SUM-TD scores than those with other diagnoses (P<0.001).
5 patients had TD at study endpoint, while the 12 patients who had TD at study entry had recovered at endpoint.
All analyses of AIMS ratings were non-significant
NRMultiple analyses with subgroups and subcomparisions by diagnosis. I had a hard time piecing out the different results and what groups were being compared.
Faries, 2008, United StatesPost-hoc analysis using data from the risperidone arm of a randomized trialRetrospectiveJuly 1997 – September 2002Pre-switch (risperidone)/Post-switch (olanzapine) (days)
85.9±77.7/241.8±108.3
Pre-switch (risperidone)/Post-switch (olanzapine) (mg/day):
Mean maximum = 4.7/13.7
Diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder, greater than 18 years of age, and randomized to risperidone therapy and either switched or did not switch to olanzapine therapySwitchers/Non-switchers
Mean Age ± SD (years):
43±13.1/42.2±11.5
Gender (% female):
60.5/34.2
Ethnicity (%):
Caucasian: 55.8/54.4
African American: 30.2/34.8
Other: 14.0/10.8
NR
221
218
NR
NR
201
NASwitchers/Non-switchers:
Weight (mean±SD, in Kg):
Baseline=87.8±20.2/87.6±21.5
Endpoint=90.7±22.8/90.1±21.9
Change=1.4±3.7/0.4±3.9
Small size and no comparative group
Fleischhaker, 2006, GermanyFour child and adolescent psychiatric departments in four mental heath centers in GermanyProspectiveNRMean = 7.4 weeksClozapine/Olanzapine/Risperidone
Mean dose (mg): 321.9±156.5/16.6±7.1/3.9±1.7
Dose range (mg): 125.0–600.0/7.5–30.0/1.0–6.0
Adolescent inpatients (n=51) who started treatment with clozapine (n=16), olanzapine (n=16), and risperidone (n=19) in open clinical trials

31 adolescents had a diagnosis of schizophrenia
Clozapine/Olanzapine/Risperidone
Mean age (y±SD): 17.2±1.8/15.8±1.4/15.6±2.6
Gender (n male): 11/9/13
Ethnicity: NR
NR
NR
51
NR
NR
51
NAClozapine/Olanzapine/Risperidone
Tardive dyskinesia (n,(%)): 0(0)/0(0)/0(0)
Weight gain (n,(%)): 9(56.3)/11(68.8)/7(36.8); p=0.16
Mean weight gain after 6 weeks (kg): 2.5/4.6/2.8
Comedication
Hagg, 1998
Sweden
Single site
Naturalistic: Gallivare Hospital
Cross-sectional, prevalence studyYears treated mean (range): clozapine 3 (0.1–6) typical APs 6 (0.2–22)No follow-up (snapshot)Clozapine
Typical APs
Mean dose NR
Patients treated with clozapine or typical APs at the time study was conducted.

85% schizophrenia
4.6% paranoid psychosis
3% cycloid psychosis
3% affective/schizo- affective psychosis
Mean age: clozapine 41, typical APs 48
59% male
Ethnicity NR
214/142/130
Clozapine n=63
Typical APs n=67
NR
NR
130 analyzed
NRClozapine vs typical APs, Prevalence:
Hyperglycemia 33 vs 19% (p=0.07)
Type 2 diabetes 12 vs 6% (ns)
Impaired glucose tolerance (IGT) 10 vs 3% (ns)
Type 2 DM or IGT 22 vs 10% (p=0.06)

Women with type 2 diabetes or IGT, clozapine vs typical APs:
9/27 (33.3%) vs 2/26 (7.7%) (p=0.04)

Body mass index, all subjects:
27 vs 28 kg/m2 (ns)
Body mass index, subjects with diabetes mellitus or IGT:
27 vs 30 kg/m2 (ns)
12 (19%) clozapine subjects had concomitant treatment with typical APs, most often haloperidol (n=6).

Body mass index was similar between clozapine patients with and without diabetes/IGT.

Clozapine patients tended to be younger and treated for fewer years than patients on typical APs.
Henderson, 2000
United States
Chart review: outpatient clinic of urban mental health centerRetrospective5 yearsNRClozapineSchizophrenia
Schizoaffective disorder
Mean age=36.35
73.2% male
91.5% white
NR
101
82
NR
NR
82
NRDiagnosis of Type II Diabetes=30/82 (36.6%)

Weight gain: linear coefficient of 1.16 lb/month (SE=0.18) (mixed-effects model, t-6.62, df- 80, p=0.0001)
Henderson, 2005
United States
Autopsy reports, medical recordsRetrospectiveJanuary 1992 to December 200390 monthsClozapine; dose NRSchizophrenia
Schizoaffective disorder
Mean age=36.5 years
72% male
89% white
NR
NR
96
N/A
N/A
96
NRKaplan-Meier estimates for overall 10-year:
Mortality=9%
New-onset diabetes=34%
Herrman et al, 2004
Canada
Database: administrative health care databases in Ontario, CanadaRetrospectiveApril 1, 1997 through March 31, 2002NRRisperidone
Olanzapine
Typical antipsychotics
Patients over age 65 who were given at least 2 successive prescriptions and received enough drug for at least 30 days of observation.Mean age approximately 82 years (SD 7.5)
69% female
Ethnicity not reported
NR
NR
11,400
NR
NR
11,400
NRSubgroup Hospital admission analyses for stroke: odds of mortality (95% CI)
typical antipsychotic users: N=10
risperidone users: N=58
olanzapine users: N=24
Crude stroke rate per 1.000 person years:
typical antipsychotic users: 5.7
risperidone users: N=7.8
olanzapine users: N=5.7 (NS)
RR relative to typical antipsychotic use:
olanzapine: 1.1 (95% CI 0.5, 2.3)
risperidone: 1.4 (95% CI 0.7, 2.8)

RR of risperidone relative to olanzapine: 1.3 (95% CI 0.8, 2.2)
Hofer, 2003
Austria
inpatients unit of the Department of Psychiatry of Innsbruck University ClinicsProspective1989–19968 weeksClozapine 263.5 mg/day for at least 8 weeksSchizophrenia or schizophreniform disorderMean age=28.7 years
75.5% male
Ethnicity: NR
NR/NR/95NR/NR/95Multiple linear regression: only age found to be a significant predictor of CGI (F=4.22, p=0.045)1 seizures
1 increased liver enzyme level
Frequently reported side effects: week 1–3(%) vs week 4–6(%)
First episode (n=39)
 concentration difficulty: 51.3 vs 13
 asthenia: 48.7 vs 26.1
 sedation: 20.5 vs 0
 failing memory: 25.6 vs 0
 increased duration of sleep: 41.3 vs 30.4
 increased salivation: 28.2 vs 17.4
 diminished sexual desire: 41.0 vs 13.0
Multiple episode (n=556)
 concentration difficulty: 55.3 vs 31.5
 asthenia: 53.6 vs 25.8
 sedation: 35.7 vs 20.0
 failing memory: 28.6 vs 17.1
 increased duration of sleep: 39.3 vs 25.7
 increased salivation: 23.2 vs 8.6
 diminished sexual desire: 35.8 vs 25.7
Honigfeld, 1996
United States
Database: Clozapine National Registry SystemUnclear2/1990 to 12/1994NRClozapineTreatment resistant schizophreniaNR
NR
NR
NR
NR
99,502
NR
NR
99,502
NRAgranulocytosis
Cases=382(0.38%)
Fatal cases=12(0.012%)
Kane, 1994
United States
the inpatients service at Hillside HospitalProspectiveNR52 weeksClozapine 599 mg/day
52 weeks
Schizophrenia or schizoaffective disorderMean age=27.6 years
66% male
84% white; 14% black; 2% other
NR/NR/56NR/NR/34Correlations of Simpson-Angus Akinesia item with BPRS anergia factor: r, p value
 baseline (n=56): 0.68, p=0.00
 week 3 (n=49): 0.59, p=0.00
 week 6 (n=47): 0.43, p=0.00
 week 12 (n=27): 0.48, p=0.01
 week 26 (n=28): 0.40, p=0.03
 week 39 (n=24): 0.37, p=0.07
NR
Killian, 1999
Australia
Adverse Drug Reactions Advisory Committee (ADRAC) of AustraliaUnclearJan. 1993 to March 1999NRClozapine range: 100–725 mg/d

myocarditis pts took cloz. a median of 15d (range: 3 – 22d) before myocarditis developed

Cardiomyopathy pts took cloz. a median of 12 months (range: 2–36 m) before cardiomyopathy developed
Clozapine-using patients

(article did not specify diagnosis of pts in registry)
Mean age: 36y

87% male

Ethnicity: NR
8000/43/33NR/NR/33NRCardiomyopathy: 8 cases (of 8000 clozapine pts; 0.10%)
Myocarditis: 15 cases (of 8000 clozapine pts; 0.19%) (10 additional cases were not supported by objective clinical or investigational findings)

Deaths: 33.3% (5 of 15) myocarditis pts and 12.5% (1 of 8) cardiomyopathy pts died
Kim, 2008, South KoreaDepartment of Psychiatry, Bundang CHA General Hospital, South KoreaProspectiveDecember 2004 – July 2007NR85.9±77.7/241.8±108.3Patients with first-episode schizophrenia or schizoaffective disorder, between 17 and 60 years of age, with an IQ above 80, and receiving treatment of long-acting injectable or oral risperidone as outpatientsRLAI/Oral
Age (years): 32.5±10.6/31.0±10.1
Gender (%male): 32/40
Ethnicity: NR
NR
55 (25 assigned to risperidone long- acting injection (RLAI) group, 30 assigned to oral risperidone group)/50 (22 assigned to RLAI group, 28 assigned to oral risperidone group)
NR
NR
50
1-year medication compliance (%mean±SD):
RLAI = 85.7±21.4
Oral risperidone = 54.3±32.8
2-year medication compliance (%mean±SD):
RLAI = 81.4±26.6
Oral risperidone = 54.6±32.1
Non- or partial adherence (%):
RLAI = 32%
Oral risperidone = 68%
Good adherence (%):
RLAI = 68%
Oral risperidone = 32%
1-year relapse (%):
RLAI = 18%
Oral risperidone = 50%
2-year relapse (%):
RLAI = 23%
Oral risperidone = 75%
Tardive dyskinesia was observed in one patient in the RLAI groupSample size was small
Koller, 2001 United StatesMedWatch Drug Surveillance SystemRetrospectiveJanuary 1990 to February 2001NRClozapine 362 mgclozapine-associated diabetes or hyperglycemiaMean age=40 years
Gender: NR
Ethnicity: NR
NR/NR/384NA/NA/384NRclozapine was discontinued in 110 cases (54 cases follow-up were available)
 42 improved in metabolic status
 11 had no change in metabolic status
 26 no longer required hypoglycemic drug therapy
 18 glucose levels returned to normal
80 patients had metabolic acidosis or ketosis accompanied the hyperglycemia
 73 with new-onset diabetes (blood glucose level >= 500 mg/dL)
 51 with new-onset diabetes
(blood glucose level >= 700 mg/dL)
 32 with new-onset diabetes occurred within 3 months of the initiation of clozapine therapy (blood glucose level >= 700 mg/dL)
 26 had acidosis or ketosis
25 died during hyperglycemic episodes
 16 had acidosis or ketosis
146 patients had body weight data
 38 had no clear evidence of obesity or substantial weight gain
Kopala, 2005
Canada
Nova Scotia Early Psychosis Program in HalifaxProspective open- label dose ranging studyNA2 yearsStarting dose of quetiapine was 25 mg and then the dose was titrated up to a maximum of 800 mg/day depending on symptom response and tolerability.Inpatients (n = 10) and outpatients (n = 29), ages of 17 and 42 who met DSM IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Subjects with > 6 months of cumulative exposure to antipsychotic medications or had been psychotic > 2 years were excluded.Mean age 23.2 years
82.1 % male
100% Caucasian
NA19/19/20See safety outcomesBMI and weight at baseline and 24 months grouped by
BMI less than 25
Base BMI 21.5 weight 67.0 kg
2 yrs BMI 25.6 weight 79.1 kg
BMI baseline vs. 2 years P < 0.001
BMI 25 or greater
Base BMI 29.1 weight 84.3 kg
2 yrs BMI 30.3 weight 86.7 kg
BMI baseline vs. 2 years P < 0.001
Kozma, 2004 (poster)
United States
Database:
Medstat's Medicaid database
Retrospective1999–2002NRAtypical antipsychotics overall
Olanzapine
Risperidone
Quetiapine
Haloperidol
Benzodiazepines
Age 60 or older, evidence of dementia treatment (2 or more claims containing a primary or secondary diagnosis of dementia), initial use (I.e., following a 6- month or longer period of no use) of 1 of 3 classes of drugs: atypical antipsychotics (risperidone, olanzapine, or quetiapine), haloperidol, or benzodiazepines.Median age 78–82 among groups;
Among patients taking atypical antipsychotics, 56% were Caucasian, 17% African American; among patients taking conventional antipsychotics, 45% were Caucasian and 21% African American.
NR
NR
26,456
NR
NR
26,456
NRStroke-related event (defined as an acute inpatient hospital admission for a stroke-related event within 90 days following initiation of treatment with the index medication):
Unadjusted rates were not statistically significant, reporting is unclear: states rates were: 0.87%, 0.97%, 0.88%, 0.58%, 1.19%, 1.11% 1.04% for atypical antipsychotics overall, olanzapine, risperidone, quetiapine, haloperidol, and benzodiazepine groups, respectively.
Lasser, 2004
Europe and Canada
Europe and Canada multicenter trialProspective12 months239 daysRisperidone 25mg, 50mgSchizophrenia or schizoaffective disorderMean age: 70.9 years
53% male
100% white
725/57/57NR/1/57baseline vs change at endpoint, p vs baseline
PANSS total: 73±2.1 vs −10.5±1.5, p<0.001
 Positive symptoms: 20.6±0.8 vs −3.2±0.6, p<0.001
 Negative symptoms: 19.7±0.8 vs −2.8±0.5, p<0.001
 Disorganized thoughts: 17.7±0.7 vs −2.0±0.4, p<0.001
 Anxiety/depression: 8.2±0.5 vs −1.6±0.4, p<0.001
 Hostility/excitement: 6.8±0.4 vs −0.9±0.3, p<0.01

baseline vs endpoint
 CGI- not ill or with very mild or mild illness: 28% vs 69%
 CGI- marked or severe illness: 14% vs 0%

CGI- at least 1 point improvement in CGI severity scores: 55%
42(74%) reported adverse events
insomnia: 14%
constipation: 12%
bronchitis: 12%
psychosis: 11%
rhinitis: 11%

1 died with a myocardial infarction

baseline vs mean change at endpoint, p vs baseline
ESRS total: 10.2±1.5 vs −3.1±0.8, p<0.001
Patient questionnaire: 4.0±0.7 vs −1.4±0.5, p<0.01
Parkinsonism total: 10.6±1.5 vs −3.6±0.9, p<0.001
Parkinsonism severity: 1.7±0.2 vs −0.4±0.2, p<0.05
Dyskinesia total: 2.7±0.7 vs −0.6±0.3, NS
Lasser, 2004
United States
NRProspectiveNR8 weeksOlanzapine or risperidone for 8 weeksSchizophrenia or schizoaffective disordersMean age=49.9 years
60.8% male
63.6% white
NR/NR/552NR/NR/375NRpatients with >= 7% weight increase
olanzapine adult smokers: 25/82(30.5%)
olanzapine adult nonsmokers: 16/55(29.1%)
olanzapine elderly smokers: 4/27(14.8%)
olanzapine elderly nonsmokers: 4/35(11.4%)
risperidone adult smokers: 11/82(13.4%)
risperidone adult nonsmokers: 7/43(16.3%)
risperidone elderly smokers: 0/20(0%)
risperidone elderly nonsmokers: 3/31(9.7%)
Pearson's correlation analysis between smoking and weight:
risperidone-treated patients: r = −0.037
olanzapine-treated patients: r = 0.029
Lieberman, 1992
Alvir 1993
United States
Database: Caremark Patient Monitoring System (CPMS) from 2/5/90 to 4/30/91Unclear>/= 3 weeksNRClozapine mean maximum dose=451.9 mgSchizophreniaMean age NR
62% male
Race NR
17,042
11,555
11,555
NR
NR
11,555
NRAgranulocytosis
# cases/fatal cases=73/2
Cumulative incidence (year1/year1.5): 0.8%/0.91%
Lindstrom, 1989
Sweden
Hospital records and interviewsRetrospectiveJuly 1, 1974 to December 31, 1986NRClozapineSchizophrenia or schizoaffective disordersMean age (years): 36.1
66% males
NR/NR/992/3/96More than one third of participants significantly improved while on clozapine, while another one third moderately improved.
35 patients discontinued treatment of clozapine during the study period, 8 of those showed significant improvement before stopping the medication
At the initiation of clozapine 3 patients were employed, however 2 yeas later, of those still on clozapine, 24 were employed.
2 patients withdrew from the study due to leukopenia or agranulocytosis, neither were fatal outcomes.
Common, but usually mild side effects included: sedation, hypersalivation, weight gain, and obstipation.
4 patients experienced grand mal seizures while on clozapine, however these were controlled with other medications.
4 patients died while on clozapine, however there was no direct correlation found between the deaths and the use of clozapine, 2 of these deaths were suicides.
Lindstrom, 2007, SwedenPatients enrolled in a national, multicenter, point-prevalence, 5- year longitudinal Phase IV trialProspective1995–2000VariableNRPatients with schizophrenia or a related disorder according to DSM-IV and treated with risperidone as the main antipsychotic drug for at least 1 month. During the following 5 years, some patients were switched to other antipsychotic compounds or were drug-free

Males and females >18y; in- and out- patients; responders or partial responders to antipsychotic drugs
Background variables of all included patients (n=225)
Age (y): 38.5±11.7 (range 18–79)
Gender (n male): 132
Ethnicity: NR
Exposed:225
Eliglble:225
Selected:101
Withdrawn: NR
Lost to FU: NR
Analyzed: 101
Frequency of Parkinsonism/dystonia according to the ESRS instrument over 5 years (Score 0–1/Score 2–4/Score 5–6/n):
495/574/240/158/10/13/745

Abnormal involuntary movements:
23 of 166 patients (14%) had TD

Social Outcomes:
Mean number of days in hospital decreased from 41 to 10 days
Mean number of days in sheltered accommodations increased from 28 to 63
Net decrease in the number of patients who lived independently from 83% to 71%
One patient (of 101) had 365 hospital days during year 5, and 9 others had any hospital days (range 3–138)
15–26% of patients had no social contacts (except with health service staff)
29–37% reported meeting friends or peers <1 time per week
12% of patients worked or studied full-time
14% worked or studied half-time
75% were on sick leave or had disability pension

Mortality:
8 patients died during the 5 year trial
Lund, 2001
United States
Database: Iowa Medicaid program claims/prescription databaseUnclear1990 to 1994Clozapine=25.5 months
Typical APs =24.5 months
Clozapine
Typical Antipsychotics
SchizophreniaMean age=41.9
59.2% male
Race NR
NR
4770
3013
NR
NR
3013 (clozapine=552, CAPD=2461)
NRDiabetes
Total cohort
21 (4%) vs 78 (3.4%); p=0.62
Patients aged 20–34
11/222 (5%) vs 15/768 (2%)
RR 2.5, 95% CI 1.2 to 5.4
Age
Maskasame, 2007, ThailandMedical record review: Srinagarind Hospital, Khon Kaen, ThailandRetrospectiveNR2 yearsDoses were recorded but no mean dose was reported. Patient who developed neutropenia received 25mg/day of clozapineSchizophrenic out-patients who received clozapine from January 1, 2003–December 31, 2005Mean Age: 32 years; % Male: 58.5%, Ethnicity: NRNR/117/650/0/65NRNeutropenia was found in one patient (incidence rate = 1.5%, incidence density = 0.01/year). No leukopenia or agranulocytosis were found.WBC was not checked before starting clozapine in patient who developed neutropenia
Mladsi, 2004
United States
Three acute care inpatient mental health facilitiesRetrospectiveMay 1, 1998 and June 30, 2000Length of stay- less than 30 daysRisperidone 4.45 mg
Olanzapine 14.04 mg
Quetiapine 350.33 mg
Schizophrenia 59%
Schizoaffective 41%
Mean age 40 years
62% male
52% white
39% black
9% other
NR
NR
327
NA
NA
327
Mean length of stay was 12.4 days (SD 6.5) for risperidone patients, 11.3 days (SD 5.7) for olanzapine patients, and 13.7 days (SD 6.5) for quetiapine

GAF scores at discharge (45.9 [SD 10.3] for risperidone, 46.2 [SD 10.1] for olanzapine, and 44.3 [12.2]
for quetiapine)
NR
Munro 1999
UK and Ireland
Clozapine drug registry reviewRetrospectiveNRJanuary 1990 – April 1997Mean clozapine dose after 12 w treatment: 388 mg/day (95% CI 384–391)
Mean maximum clozapine dose: 462 mg/day (95% CI 458–466)

41% of subjects had a peak dose >500 mg/day; 5% of subjects exceeded the recommended maximum dose of 900 mg/day
Treatment-resistant schizophrenic patients prescribed clozapineMean age (at 1st blood test): males: 35.4 y (range 9.6–84.1); females: 39.7 y (range 13.8–90.4)
Male: 67 %
Ethnicity: 89% Caucasian; 5% African-Caribbean origin; 4% Asian; 2% mixed race; <1% Oriental
NR
NR
12760
Withdrawn: 283
Caucasian and 33 African-Caribbean subjects withdrew due to neutropenia
All other withdraws NR
Lost to FU: NR
Analyzed: 12760
Agranulocytosis:
Cumulative incidence: 0.73%
Peak risk occurred at 6–18 weeks with an incidence of 0.7%
Mortality rate: 0.016%
For each 10 year increase in age on starting clozapine, the hazard of developing agranulocytosis increased by 53% (P=0.0001, hazard ratio 1.528, 95% CI 1.315–1.777)
Compared with Caucasians, Asian subjects had 2.4 times the risk of developing agranulocytosis (P=0.03, hazard ratio 2.388, 95% CI 1.098–5.194)
The risk in Oriental/Mixed-race and African-Caribbean subjects was nonsignificant (P=0.84, P=0.61, respectively)
For each 100mg increase in the maximum dose the risk of agranulocytosis decreased by 21% (P= 0.0001; hazard ratio 0.787, 95% CI 0.702–0.882)

Neutropenia:
Cumulative incidence: 2.7%
Peak risk occurred at 6–18 weeks with an incidence of 1.27%
For each 10 year increase in age on starting clozapine, the hazard of developing neutropenia decreased by 17% (P=0.0003, hazard ratio 0.834, 95% CI 0.756–0.919)
The hazard ratio for African-Caribbean subjects was 1.77 (95% CI 1.208–2.583, P=0.0033)
There was no significant difference in Oriental/Mixed-race or Asian subjects (P=0.25 and P=0.497, respectively)
For each 100mg increase in the maximum dose the risk of neutropenia decreased by 31% (P= 0.0001; hazard ratio 0.688, 95% CI 0.647–0.731)

Monitoring Interval:
Four-weekly/Two-weekly
# subjects treated: 5199/1510
# of hematological fatalities: 0/0
# (%) of neutropenia cases: 13 (0.25)/71 (4.7%)
# (%) of agranulocytosis cases: 2 (0.04)/4 (0.26)
Incomplete tables, poor data presentation
Perez, 2008, Spain77 acute hospital units in SpainProspectiveMarch 2002 – October 2004Acute: admission to discharge, and Long-term: discharge to 12 monthsMean doses at discharge:
quetiapine = 719.6 mg/day
risperidone = 8.0 mg/day
Mean doses at 12 months:
quetiapine = 718.5 mg/day
risperidone = 7.0 mg/day
Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder who were prescribed quetiapine or risperidone within the first week of treatmentQuetiapine/Risperidone:
Mean age: 37.2/36.4
Gender (% male): 63.6/67.8
Ethnicity: NR
NR
492
Selected:
Intent to Treat population: 466 (quetiapine=345, risperidone=121)
Per protocol population: 422 (quetiapine=311,
risperidone=111)
Safety population:
470 (quetiapine=349,
Quetiapine/Risperidone:
Withdrawn: NR
Lost to FU:
time of discharge:
43/9
6-month follow-up:
89/28
12-month follow-up: 31/13
Analyzed:
baseline: 345/121
time of discharge: 324/116
Rastogi, 2000
UK
NRProspectiveNR6 monthsclozapine 150–300 mg
6 months
SchizophreniaMean age=37.8 years
71% male
Ethnicity: NR
NR/NR/31NR/NR/31Global impression:
 21(67.7%) patients were rated as improved by clinicians
 18(58.1%) patients self-rated as improved
Six monthly outcome measure for the basic everyday living skills scale: Mean % improvement
 self-care: 15%
 domestic skills: 20%
 community skills: 17%
 activity and social skills: 22%
NR
Reid, 1998
United States
Database: Texas MH SystemUnclear1991 to 1996NRClozapineSchizophrenia/SchizoaffectiveNR
NR
NR
NR
NR
NR
NR
NR
NR
NRSuicide
1 case
Annual rate=12.74 per 1000,000
Still, 1996
United States
a 400-bed state psychiatric hospitalProspectiveApril to August 199412 weeksRisperidone titrated a week to 3mg twice daily. The mean dosage for the five subjects who completed 12 weeks treatment is 7.6 mg at week 9 and 8 mg at week 12.Schizophrenia or schizoaffective disorderMean age=41.2 years
60% male
Ethnicity: NR
NR/NR/105/0/5No subjects improved after being switched to risperidone
PANSS, LPCF increased from baseline, but no significant changes: patients who were switched from clozapine tended to worsen when taking risperidone (data NR)
The mean total scores on the PANSS, the PANSS positive symptom subscale and the BPRS met the study's 20% criterion for a clinically significant change at week 6 through week 12 (data NR) CGI scores: 2 no change; 3 minimally worse; 4 much worse; 1 very much worse
3 decreased concentration
3 impaired memory
4 irritability
3 akathisia, confusion
Akathisia scale showed significant different worsening of symptoms
Patients switched from clozapine to risperidone
Tadger, 2008, IsraelInpatients and their files from inpatient rehabilitation and day care unitsProspective (some data was collected retrospectively, however)NROne year or longer for patients treated with second- generation antipsychotic agents; NR for patients treated with first-generation antipsychoticsNRInpatients treated with second-generation antipsychotics for 1+ year (n=70), and inpatients treated with first-generation antipsychotics (n=30).
91% of subjects were diagnosed with schizophrenia, 9% were diagnosed with other psychiatric disorders.
Mean age: 47.4±12.4 years
Gender: 60% male
Ethnicity: NR
NR
NR
100 (risperidone N=40, olanzapine N=30, typical N=30)
NR
NR
NR
N/AIncrease/decrease in BMI (%):
1.00 (lost weight):
typical=23.3
risperidone=17.9
olanzapine=6.9
0.00 (maintained weight):
typical=50.0
risperidone=59.0
olanzapine=48.3
1.00 (gained weight):
typical=26.7
risperidone=17.9
olanzapine=37.9
2.00 (gained weight):
typical=N/A
risperidone=5.1
olanzapine=3.4
3.00 (gained weight):
typical=N/A
risperidone=N/A
olanzapine=3.4
Taylor, 2009, UKPharmacy computer recordsRetrospectiveClozapine group: March 2002–October 2006
Risperidone group: August 2002–October 2004
Clozapine/Risperidone
Mean duration of treatment (months) (mean±SD):
12.3±18.6/5.9±8.7
Clozapine/Risperidone:
Mean dose at cessation (mg/day) (mean±SD):
360±159/34.5±12.2
161 Clozapine discontinuers matched with 161 Risperidone discontinuersClozapine/Risperidone
Age at discontinuation (mean±SD) (y):
40.0±12.6/39.9±13.1
Gender (n male): 99/99
Ethnicity (n):
White: 72/61
Black (African/Caribbean): 61/79
Asian: 13/9
Mixed 15/12
Clozapine/Risperidone
Exposed: 592/277
Eligible: 224/250
Selected: 161/161
Clozapine/Risperidone
Withdrawn: NR/NR
Lost to FU: NR/27
Analyzed: 161/161
Death as a reason for discontinuation (n, (%)):
Clozapine/Risperidone/OR (95% CI)/McNemar's x2, df=1
21 (13.0)/3 (1.9)/7 (2.09–23.5)/13.5 (p=0.0003)

Clozapine/Risperidone:
Mortality rate: 8.5 (95%CI 5.53–13.07) per 1000 patient years/5.3 (95% CI 1.7–16.61) per 1000 patient years
Funder: Janssen-Cilag, Novartis, IVAX
Umbricht, 1994
United States
Chart reviewRetrospective12 monthsClozapineSchizophreniaMean age=28.7
68% male
85.4% white
NR
NR
82
NR
NR
68
NR60% with ≥ 10% weight gain72% neuroleptic-treatment resistant
Wilson, 1993
United States
Second paper in a series studying clozapine-treated pts in Dammasch State Hospital; this study analyzed the pts entered into the cohort in the first year
Chart review of first 100 pts starting clozapine treatment (Dammasch State Hospital; Wilsonville, Oregon)UnclearMay 1990 to December 19911 year follow-up (as well as review of 6 months prior to start of clozapine treatment); at 1 year follow up 37 pts had been discharged to community and 63 pts remained hospitalizedClozapine begun at 25 mg/d and titrated upwards;

Mean clozapine dose for pts at 3 months was 463 mg/d;
Mean dose for pts who remained hospitalized and continued clozapine 564 mg/d
Schizophrenia: 67%;
Schizoaffective disorder: 26%;
Bipolar with psychotic features: 6%;
Organic delusional disorder: 1%

12% had previous history of seizures − 8% idiopathic and 4% followed head trauma
Mean age: 37y
Range: 20–61y

55% male

94% white
NR/NR/1009
NR
100

1 pts dropped out after leukopenia and 1 pts dropped out after seizure
NRSeizures: 10% of pts (5 men and 5 women) had at least 1 seizure; they occurred at a mean dose of 323 mg/d
Of the 10 pts with seizures: 6 pts were smokers, 4 were nonsmokers
4 pts of 12 with previous history had seizures; 6 of 88 pts without this history had seizures
1 of 9 pts with previous head trauma had seizure
1 pt reported to have died of pneumonia (not related to drug) 4 mos after discontinuing clozapine

From: Evidence Tables

Cover of Drug Class Review: Atypical Antipsychotic Drugs
Drug Class Review: Atypical Antipsychotic Drugs: Final Update 3 Report [Internet].
McDonagh M, Peterson K, Carson S, et al.
Portland (OR): Oregon Health & Science University; 2010 Jul.
Copyright © 2010 by Oregon Health & Science University, Portland, Oregon 97239. All rights reserved.

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