Evidence Table 16Placebo-controlled trials in patients with behavioral and psychological symptoms of dementia

Author, year
Counnry
Trial name (Quality score)
NDurationStudy design
Setting
Eligibility criteriaExclusion criteriaInterventions (drug, dose, duration)Run-in/washout periodAllowed other medications/interventionsAge
Gender
Ethnicity
Other population characteristics (diagnosis, etc)Number screened/eligible/enrolledNumber withdrawn/lost to fu/analyzedOutcome scalesMethod of outcome assessment and timing of assessmentResultsMethod of adverse event assessmentAdverse events
Olanzapine (oral)
Street, 2000
US (GOOD)
Kennedy, 2001 (subanalysis)
Street 2001 (one-year followup)
2066 weeksDouble-blind, multicenterElderly nursing care facility residents, who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for possible or probable Alzheimer's Disease. Score of 3 or higher on any of the Agitation/Aggression, Hallucinations, or Delusions items of the Neuropsychiatric Inventory-Nursing Home version (NH-NH) at screening and following placebo lead-in.History of a DSM-IV Axis I disorder (e.g., schizophrenia, bipolar disorder, severe or recurrent depression), any neurological condition other than Alzheimer's disease that could contribute to psychosis or dementia, MMSE score of greater than 24, and bedridden status.olanzapine 5 mg, 10 mg, or 15 mg3- to 14-day single-blind placebo run-in; patients demonstrating a placebo response were not randomized.Benzodiazepines allowed as rescue medication but could not exceed 4 mg/day of lorazepam equivalents for a total of 21 days during the active treatment.Mean age 83 yearsAlzheimer's Disease# screened not reported/288 eligible/206 enrolled54 withdrawn/5 lost to followup/200 analyzedPrimary outcome measure: Neuropsychiatric Inventory-Nursing Home version (NH-NH) item scores for the core symptoms:
Agitation/Aggression, Hallucinations, and Delusions.

Secondary measures: NH/NH Total, Hallucinations and Delusions total (Psychosis Total), individual items, Occupational Disruptiveness score derived from the Agitation/Aggression, Hallucinations, and Delusions items (Core Disruptiveness), Brief Psychiatric Rating Scale total and subscale, MMSE
Assessments conducted at the nursing facility by neurologists, psychiatrists, geriatricians, psychometrists, nurses, and other medical specialists trained before study initiation. At screening, baseline, and end of study.Mean change from baseline, Olanzapine vs placebo (p vs placebo):
NPI/NH (Core Total)
5 mg -7.6 (p<0.001); 10 mg -6.1 (p=0.006); 15 mg -4.9 (p=0.24); placebo -3.7
NPI/NH (Occupational Disruptiveness)
5 mg -2.7 (p=0.008); 10 mg -2.1 (p=0.28); 15 mg -2.3 (p=0.14); placebo -1.5
NPI/NH (Agitation/Aggression)
5 mg -4.1 (p=0.01); 10 mg -3.9 (p=0.02); 15 mg -3.1 (p=0.60); placebo -2.1
NPI/NH (Psychosis Total)
5 mg -3.6 (p=0.001); 10 mg -2.2 (p=0.04); 15 mg -1.9 (p=0.20); placebo -1.6
NPI/NH (Hallucinations)
5 mg -0.7 (p=0.007); 10 mg -0.2 (p=0.05); 15 mg -0.7 (p=0.10); placebo 0.0
NPI/NH (Delusions)
5 mg -2.9 (p=0.01); 10 mg -2.0 (p=0.15); 15 mg -1.3 (p=0.64); placebo -1.6
NPI/NH (Depression/Dysphoria)
5 mg -2.0 (p=0.28); 10 mg -0.6 (p>0.99); 15 mg -0.2 (p=0.32); placebo -1.0
NPI/NH (Total)
5 mg -18.7 (p=0.005); 10 mg -14.0 (p=0.09); 15 mg -9.7 (p=0.83); placebo -10.4
BPRS (Total)
5 mg -6.8 (p=0.005); 10 mg -5.6 (p=0.06); 15 mg -4.0 (p=0.13); placebo -1.4
BPRS (Positive subscale)
5 mg -2.0 (p=0.05); 10 mg -1.4 (p=0.40); 15 mg -1.4 (p=0.15); placebo -0.4
BPRS (Anxiety/Depression subscale)
5 mg -1.3 (p=0.04); 10 mg -1.5 (p=0.02); 15 mg -0.6 (p=0.29); placebo 0.1
Simpson-Angus Scale, Barnes Akathisia Scale, AIMSWithdrawals due to adverse events:
11% olanzapine 5 mg
8% olanzapine 10 mg
17% olanzapine 15 mg
4% placebo
No statistically significant mean changes on Simpson-Angus Scale, Barnes Akathisia Scale, AIMS. Incidence of spontaneously reported EPS (tremor, hypertonia, cogwheel rigidity, hyperkinesia, akathisia, dyskinesia, dystonia, parkinsonism, tardive dyskinesia) was not significantly different from placebo.
No differences between active treatment groups on any event
de Deyn, 2004 Europe, Australia, Israel, Lebanon, and South Africa (FAIR)65210 weeksDouble-blind, multicenterAge 40 or older, resided in long-term nursing homes or continuing-care hospitals, and expected to continue patient status for 6 months following enrollment. Met NINCDS-ADRDA and DSM-IV - TR criteria for possible or probable Alzheimer's Disease, and exhibited clinically significant psychotic symptoms (delusions or hallucinations) that were (1) at least moderate in severity (i.e., impair functional capacity or cause them to pose a threat to themselves) at study entry and randomization; (2) present at least once per week for the month preceding study entry; and (3) require pharmacological intervention, in the opinion of the investigator. Minimum score of 5 on MMSE at Visit 1 and Visit 2.Diagnosis of current primary mood disorder or other DSM-IV Axis I disorder with onset prior to diagnosis of Alzheimer's disease, including but not limited to schizophrenia, bipolar disorder, or delusional disorder.olanzapine 1 mg, 2.5 mg, 5 mg, 7.5 mg, or placebo 10 weeks, fixed dose. Those assigned to 5 mg or 7.5 mg began at 2.5 mg and titrated to final dose by 2.5 mg per week increments.Placebo run-in for up to maximum 14 days.Medications with primarily central nervous system activity were disallowed, except for the stable use of antidepressants, benzodiazepines, and acetylcholinesterase inhibitors.
Use of anticholinergics for control of EPS was exclusionary. Limited use of benzodiazepines or hypnotics permitted with restrictions as a rescue medication to chronic users up to 4 mg/day
Mean age 77 (sd 10.4)
75% female
99.7% white
Mean baseline
MMSE score 13.7 (sd 5.1); mean baseline NIP/NH
Psychosis Total score 9.7 (sd 4.9)
Number screened, eligible not reported/652 enrolled184 withdrawn/lost to followup not reported/642 analyzedNH-NH Total
NH-NH Psychosis
CGI-C
Responses obtained by a trained interviewer from professional caregivers involved in the ongoing care of the patient in the previous week.
Assessments weekly for the first 2 weeks of treatment and biweekly thereafter.
NPI/NH, Mean change from baseline, Olanzapine vs placebo (p vs placebo):
(Total): 1 mg -14.8 (p=0.547); 2.5 mg -15.7 (p=0.121); 5 mg -16.3 (p=0.199); 7.5 mg -17.7 (p=0.003); placebo -13.7
(Psychosis Total): 1 mg -6.0 (p<0.171); 2.5 mg -5.8 (p=0.089); 5 mg -5.6 (p=0.274); 7.5 mg -6.2 (p=0.032); placebo -5.0
(Agitation/Aggression): 1 mg -1.7 (p<0.039); 2.5 mg -1.7 (p=0.046); 5 mg -1.6 (p=0.70); 7.5 mg -2.0 (p=0.2002); placebo -1.3
(Anxiety): 1 mg -1.4 (p<0.658); 2.5 mg -1.5 (p=0.167); 5 mg -1.8 (p=0.43); 7.5 mg -1.7 (p=0.019); placebo -1.0
(Apathy/Indifference): 1 mg -1.0 (p<0.492); 2.5 mg -0.8 (p=0.174); 5 mg -0.8 (p=0.043); 7.5 mg -0.9 (p=0.612); placebo -1.1
(Delusions): 1 mg -4.3 (p<0.140); 2.5 mg -4.0 (p=0.071); 5 mg -4.2 (p=0.169); 7.5 mg -4.4 (p=0.002); placebo -3.6
(Euphoria/Elation): 1 mg -0.2 (p<0.391); 2.5 mg -0.3 (p=0.174); 5 mg -0.3 (p=0.43); 7.5 mg -0.5 (p=0.612); placebo -0.1
(Hallucinations): 1 mg -1.7 (p<0.150); 2.5 mg -1.8 (p=0.173); 5 mg -1.4 (p=0.852); 7.5 mg -1.7 (p=0.258); placebo -1.4
(Irritability/Lability): 1 mg -1.3 (p<0.154); 2.5 mg -1.3 (p=0.058); 5 mg -1.5 (p=0.007); 7.5 mg -1.6 (p=0.045); placebo -1.1

BPRS (Total): 1 mg -6.3 (p<0.405); 2.5 mg -8.7 (p=0.399); 5 mg -6.4 (p=0507); 7.5 mg -9.5 (p=0.23); placebo -6.9
BPRS (Negative): 1 mg -0.8 (p<0.342); 2.5 mg -0.9 (p=0.417); 5 mg -0.5 (p=0.122); 7.5 mg -0.5 (p=0.171); placebo -0.9
BPRS (Positive): 1 mg -2.8 (p<0.717); 2.5 mg -3.3 (p=0.167); 5 mg -2.6 (p=0.900); 7.5 mg -3.7 (p=0.21); placebo -2.7
CGI: 1 mg -3.1 (p<0.524); 2.5 mg -2.8 (p=0.030); 5 mg -2.9 (p=0.312); 7.5 mg -3.0 (p=0.2341); placebo -3.2
Simpson-Angus Scale, AIMS, mobility (gait and balance) measured with Modified Performance-Oriented Mobility Assessment-II (POMA); spontaneously reported treatment-emergent adverse events.Withdrawals due to adverse events:
9.3% olanzapine 1 mg
6.7% olanzapine 2.5 mg
7.2% olanzapine 5 mg
9.8% olanzapine 7.5 mg
3.9% placebo
Slight, non-significant improvement from baseline in each treatment group and placebo on AIMS and Simpson-Angus scales.
Treatment-emergent abnormalities based on categorical analysis of the Simpson-Angus scale showed no overall differences among treatment groups (p=0.153), ranged from 15.6% in the placebo group to 4.7% in the olanzapine 1 mg group. No other assessments of treatment-emergent abnormal motor function were statistically significant, either on the Simpson-Angus scale, or AIMS.

Deaths occurring during treatment or within 30 days after ending study participation:
olanzapine 1 mg: 4
olanzapine 2.5 mg: 3
olanzapine 5 mg: 5
olanzapine 7.5 mg: 3
placebo: 2
Most frequent cause pneumonia, no deaths considered related to study medication.
Olanzapine (short-acting IM)
Meehan, 2002 (Eli Lilly Study F1D-MC-HGHX)
US, Russia, Romania (FAIR)
27224 hoursDouble-blind, multicenter; hospital inpatients or nursing homesMale or female inpatients at least 55 years of age with a diagnosis of possible or probable Alzheimer's disease, vascular dementia, or mixed dementia. Score of 14 or above on the PANSS-EC, at least one individual PANSS item score 4 or higher, and be diagnosed with clinically significant agitation for which treatment with a parenteral agent was indicated.Patients excluded if they received benzodiazepines, antipsychotics, or anticholinergics within 4 hours prior to the first injection of study drug, if they received psychostimulants or reserpine within one week prior to study drug administration, or an injectable depot neuroleptic within less than one dosing interval of study initiation, if they had been diagnosed with any serious neurological condition other than Alzheimer's disease or vascular dementia that cold contribute to psychosis or dementia, if they had laboratory or ECG abnormalities with clinical implications for the patient's participation in the study, or if they were judged to be at serious risk of suicide.IM olanzapine 2.5 or 5 mg injection, given as 1, 2, or 3 injections over 24 hoursNot reportedNot reportedMean age 77.6 years
92.3% white
61.0% female
% with dementia type not reported331/NR/272 enrolled20/0/272PANSS-Excited Component
CMAI
Agitation-Calmness Scale
PANSS-derived BPRS total
CGI-Severity of Illness
MMSE
2 hours and 24 hours post-injectionMean change from baseline to endpoint; olanzapine (p vs placebo)
PANSS-Excited Component at 2 hours
olanzapine 2.5 mg: −7.86 (p=0.024)
olanzapine 5.0 mg: −8.67 (p=0.004)
placebo:−5.27
PANSS-Excited Component at 24 hours
olanzapine 2.5 mg: −6.44 (p=0.015)
olanzapine 5.0 mg: −6.29 (p=0.024)
placebo: −3.81
CMAI at 2 hours
olanzapine 2.5 mg: −3.77 (p=0.090)
olanzapine 5.0 mg:−3.97 (p=0.047)
placebo: −2.78
CMAI at 24 hours
olanzapine 2.5 mg: −2.82 (p=0.289)
olanzapine 5.0 mg: −3.36 (p=0.056)
placebo: −2.21
Agitation-Calmness Scale at 2 hours
olanzapine 2.5 mg: 1.80 (p=0.013)
olanzapine 5.0 mg: 1.88 (p=0.006)
placebo: 1.04
Agitation-Calmness Scale at 24 hours
olanzapine 2.5 mg: 0.90 (p=0.208)
olanzapine 5.0 mg: 1.29 (p=0.003)
placebo: 0.63
PANSS-derived BPRS total at 24 hours
olanzapine 2.5 mg: −10.51(p=0.582)
olanzapine 5.0 mg: −10.59 (p=0.560)
placebo: −10.29
PANSS-derived BPRS positive at 24 hours
olanzapine 2.5 mg: −1.72 (p=0.955)
olanzapine 5.0 mg: −1.86 (p=0.906)
placebo: −2.09
CGI-Severity of illness at 24 hours
olanzapine 2.5 mg: −0.38 (p=0.347)
olanzapine 5.0 mg: −0.47(p=0.647)
placebo: −0.59
Simpson-Angus Scale. Adverse events were detected by clinical evaluation and spontaneous report. ECGs recorded at screening and endpoint (2 and 24 hours post first injection and/or upon discontinuation after randomization)No significant change from baseline to endpoint on SAS
No withdrawals due to AEs
Treatment-emergent AES not significantly different from placebo in any active-treatment group.
Quetiapine
Ballard, 2005
UK (FAIR)
9326 weeksDouble-blind, multicenterPeople with dementia living in care facilities in Newcastle. Those with clinically significant agitation were referred by staff or physician; eligible if CMAI total score >39 and level of agitation was judged represent a clinically significant problem. Diagnosis of probable or possible Alzheimer's disease, age >60, clinically significant agitation for at least 6 weeks and scores of 4 or higher on the irritability or aberrant motor behavior scales of the neuropsychiatric inventory; and no use of antipsychotics or cholinesterase inhibitors for 4 weeks before entry into the study.Patients known to be sensitive to cholinesterase inhibitors or antipsychotics and those with advanced, severe, progressive, or unstable disease that might interfere with efficacy or put the patient at special risk; disability that might prevent them from completing study procedures; those with severe, unstable, or poorly controlled medical conditions; bradycardia ( < 50), sick sinus syndrome, or conduction defects; current diagnosis of active uncontrolled peptic ulceration within the past three months; and clinically significant urinary obstruction.quetiapine 50 mg twice daily rivastigmine 9 mg daily placebo
Titrated up to week 26
NRNRMean age 83.8 (SD 7.7)
79.6% female
Race/ethnicity NR
All had Alzheimer's Disease282/239/9327/8/81CMAI
Severe Impairment Battery
Blinded assessment at baseline, 6, and 26 weeksMean change from baseline in CMAI, quetiapine vs placebo, mean difference (95% CI; p-value)
Week 6: 3.5 (−3.7 to 10.8; p=0.3)
Week 26: 2.0 (−4.2 to 8.3; p=0.5)

Mean change from baseline in Severe Impairment Battery, quetiapine vs placebo, mean difference (95% CI; p-value)
Week 6: −14.6 (−25.3 to −4.0; p=0.009)
Week 26: −15.4 (−27.0 to −3.8; p=0.01)
Not reportedNot reported
Zhong, 2007
Full publication, replaces Zhong 2004, previously available as a poster only
US (FAIR)
33310 weeksDouble-blind, multicenterDiagnosis of dementia consistent with probable or possible Alzheimer's Disease (DSM-IV or NINCDS-ADRDA), vascular dementia (DSM-IV), or mixed dementia (DSM-IV) and clinical symptoms of agitation (Cohen-Mansfiled and Billig criteria) requiring treatment of antipsychotic medication in addition to behavioral intervention; Positive and Negative Syndrome Scale-Excitement Component (PANSS-EC) total score >14, one of the five items >4; residents in nursing homes or assisted living facilities >14 days.History of schizophrenia, schizoaffective disorder or bipolar disorder, agitation that was judged not to be related to dementia, failure to respond to a prior adequate trial of atypical antipsychotics for the treatment of agitation, and unstable medical illness (included but not limited to cardiovascular, renal, hepatic, hematological, endocrine, cerebrovascular disorders, and abnormal ECG results). Psychotropic medications with few exceptions.quetiapine 200 mg, quetiapine 100 mg or placebo.Not reportedPermitted antidepressants, hypnotics, benzodiazepines, cholinesterase inhibitors on a stable dose; hypnotics for insomnia; and lorazepam <4 mg per day or equivalent for agitation up to day 14 as needed.Mean age 83 (SD 7.5)
74% female
85% white
81% Alzheimer's dementia
9% vascular dementia
10% mixed dementia
Number screened, eligible not reported/333 enrolled114 withdrawn/lost to followup not reported/# analyzed not clearPANSS-EC (Excitement Component)
CGI-C
Not reportedLeast squares mean change from baseline (SE; p-value vs placebo for effect size)
quetiapine 200 mg vs quetiapine 100 mg vs placebo
PANSS-EC Total score: −5.7 (0.9; p=0.065) vs −4.9 (0.8; p=0.306) vs −3.9 (0.9)
CGI-C: 3.0 (0.2; p=0.017) vs 3.2 (0.2; p=0.228) vs 3.6 (0.2)
NPI-NH Total: −9.7 (2.2; p=0.546) vs −8.9 (2.1; p=0.791) vs −8.2 (2.4)
NPI-NH Agitation: −1.1 (0.5; p=0.745) vs −0.9 (0.5; p=0.467) vs −1.2 (0.5)
NPI-NH Depression: −0.4 (0.5; p=108) vs −1.1 (0.5; p=0.009) vs 0.6 (0.5)
NPI-NH Psychosis: −2.5 (0.9; p=0.985) vs −1.8 (0.8; p=0.464) vs −2.5 (0.9)
NPI-NH Occupational disruptiveness: −3.6 (0.8; p=0.460) vs −2.8 (0.7; p=0.839) vs −3.0 (0.8)
CMAI Total: −11.0 (2.1; p=0.352) vs −9.2 (2.0; p=0.877) vs −8.8 (2.3)
CMAI Physically aggressive behavior: −3.7 (0.9; p=0.976) vs −3.2 (0.9; p=0.796) vs −3.8 (1.0)
CMAI non-aggressive physical behavior: −4.0 (0.7; p=0.182) vs −4.1 (0.7; p=0.067) vs −2.9 (0.8)
CMAI verbal aggression: −3.4 (0.8; p=0.111) vs −3.1 (0.8; p=0.942) vs −3.4 (0.8)
Assessments included treatment-emergent adverse events, clinically significant changes in laboratory tests, ECGs, and vital signs. AEs recorded using MedDRA system of nomenclature and incidence rates tabulated by system organ class and preferred term.
EPS assessed by the SAS and AIMS Falls assessed at each occurrence using a modified Hendrich Fall Scale
No differences between groups on overall adverse events, withdrawals due to AEs, or change from baseline on the AIMS, SAS, or MMSE
19 deaths occurred: 5.1% quetiapine 200 mg/day, 7.3% quetiapine 100 mg/day, and 3.3% placebo. Relative risk for death for quetiapine vs placebo: 2.08 (95% CI 0.61, 7.16).
Paleacu 2008
Israel
406 weeksDB RCT in
single center
age >50 years, dementia of the Alzheimer’s type diagnosed according to DSM-IV criteria, Mini-Mental State Examination (MMSE) score <24 and a score >6 on any of the Neuropsychological Inventory (NPI) items.other types of dementia (e.g. vascular, frontotemporal lobe dementia), concomitant malignant disease, active ischemic heart disease or chronic heart failure, women of childbearing potential and alcohol or drug abuseQuetiapine median dose 200 mg vs. Placebo2 week washoutZolpidemMean age 82.2 (SD 6.4)
65% female
Placebo vs. quetiapine (SD)
MMSE 14.3 (6.8) vs. 14.5 (6.3)
AIMS 0.3 (1.0) vs. 0.9 (22, appears to be typo perhaps should be 2.2)
SAS 14.2 (3.5) vs. 15.8 (5.8)
44/40/4013/1/40NPI, CGI-S, MMSE, SAS, AIMSNPI score performed at entry, Weeks 4 and 6 and the Clinical Global Impression of Change score at entry, Weeks 2, 3, 4, 5, 6 and study end or withdrawal, MMSE score performed at study entry and end, the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale entry and Weeks 2, 4, 6 and endPlacebo vs. quetiapine
Primary outcomes reported in graphs
Decreases from baseline in NPI total score: 79% vs. 68.5%
CGI-C score decreased P = 0.480 vs. P = 0.009

MMSE 14.9 (7.3) vs. 13.5 (6.8)
At each visit patients were questioned regarding side effects and if reported these were recorded on a separate sheet and assessed as related or not to the medication and which measures were taken in consequence.Placebo vs. quetiapine
Akathisia 1 vs.. 0
Parkinsonism 1 vs. 1
Tremor 1 vs. 0
Diarrhea 1 vs. 0
Dizziness 1 vs. 0
Dry mouth 0 vs. 1
Edema 1 vs. 0
Falls 2 vs. 0
Headaches 0 vs. 1
Sedation 0 vs. 1
Confusion UTI 0 vs. 1
All 8 vs. 5
AIMS 0.2 (0.9) vs. 0.8 (2.2)
SAS14.4 (3.0) vs. 16.1 (4.9)
Trials of Risperidone
Brodaty, 2003
Frank, 2004
Australia and New Zealand
Brodaty 2005 (subgroup analysis) (FAIR)
30912 weeksDouble-blind, multicenterDiagnosis of dementia with aggressive behaviors; dementia was of the Alzheimer's type, vascular dementia, or a combination of the two, according to DSM-IV. Age 55 or older, score of 4 or greater on FAST, and 23 or less on MMSE; at least a minimum aggression score on CMAI; residing in a nursing home for at least 1 month prior to enrollment.Medical or neurologic conditions other than dementia that diminish cognitive function, other types of dementia, major depression within the last 6 months, other psychiatric disorders that could have accounted for observed psychotic disturbances, a history of tardive dyskinesia, clinically uncontrolled organic disease, clinically relevant laboratory abnormalities, administration of a depot neuroleptic within 2 treatment cycles, a history of neuroleptic malignant syndrome or an allergic reaction to neuroleptic drugs, history of failure to respond to risperidone treatment of at least 4 weeks' duration, and participation in clinical trial(s) with any investigational drugs during the 4 weeks preceding selection.risperidone oral solution 1 mg/mL, or placebo solution. Started with 0.5 mL. In case of insufficient response, dosage adjusted by increments of .5 mL no faster than every other day. Dosing was flexible throughout treatment period according to patient response and investigator judgment. Maximum dose 2 mL daily, corresponding to 2 mg risperidone.Maximum 7-day single-blind placebo washout period during which existing psychotropic medication was discontinued.Short-acting benzodiazepines allowed for treatment of insomnia, provided the dosage had been stable for at least 3 months.Mean age 83 (se 0.58)
72% female
Ethnicity not reported
58% Alzheimer's dementia
28% vascular dementia
13% mixed dementia
Number screened not reported/384 eligible/345 enrolled101 withdrawn/lost to followup not reported/304 analyzedCMAI total aggression subscale
BEHAVE-AD
CGI-S
CGI-C
MMSE
FAST

Secondary analysis:
Modified Strain in Nursing Care Assessment Scale (M-NCAS)
CMAI and BEHAVE-AD at selection, baseline, and weeks 4 and 8, and endpoint (either week 12 or patients' last visit); nurses responsible for daily care of patients were interviewed by an experienced and trained research nurse who subsequently rated the scales.
CGI-S and CGI-C evaluated at selection, baseline, weeks 1, 2, 3, 4, and 8 and endpoint by specifically trained raters and patients' primary caregivers. FAST and MMSE assessed at selection and week 12 (or last visit)

M-NCAS completed by the nurse career of individual residents at baseline, 4 weeks, 8 weeks, and 12 weeks.
CMAI, Mean change from baseline, risperidone vs placebo
(Total aggression): −7.5 vs −3.1 (p<0.001)
(Physical aggression): −5.4 vs −2.8 (p=0.008)
(Verbal aggression): −2.1 vs −0.2 (p<0.001)
(Total non-aggression): −7.3 vs −2.8 (p=0.002)
(Physical non-aggression): −4.3 vs −2.5 (p=0.71)
(Verbal non-aggression) −3.0 vs −0.3 (p<0.001)

BEHAVE-AD
(Total): −6.8 vs −2.3 (p<0.001)
(Psychotic symptom subtotal): −2.0 vs −0.7 (p=0.004)
(Paranoid and delusional ideation): −1.4 vs −0.7 (p=0.015)
(Hallucinations): −0.6 vs −0.0 (p=0.010)
(Activity disturbances): −0.8 vs −0.4 (p=0.067)
(Aggressiveness): −2.0 vs −0.5 (p<0.001)
(Diurnal rhythm disturbances): −0.3 vs −0.2 (p=0.098)
(Affective disturbance): −0.5 vs −0.2 (p=0.034)
(Anxiety and phobias): −1.1 vs −0.4 (p=0.004)

M-NCAS mean change from baseline to endpoint (analysis on subgroup of 279 patients):
Risperidone vs placebo
Attention seeking: 0.24 vs 0.09 (p<0.05)
Autonomy: 0.09 vs 0.07 (NS)
Difficulty: 0.34 vs 0.17 (p<0.05)
Total Attitude Domain: 0.24 vs 0.12 (p<0.05)
Affect: 0.26 vs 0.10 (NS)
Job satisfaction: 0.26 vs 0.09 (p<0.05)
Neediness: 0.25 vs 0.07 (p<0.05)
Predictability: 0.30 vs 0.22 (NS)
Self direction: 0.19 vs 0.11 (NS)
Total Strain Domain: 0.25 vs 0.12 (p<0.05)
Monitoring the presence and severity of EPS at each visit and ratings on the Extrapyramidal Symptom Rating Scale.Withdrawals due to adverse events:
13.2% risperidone
8.2% placebo
Mean change in Extrapyramidal Symptoms Rating Scale score:
0.5 to 2 mg: +0.7
placebo: +0.5
(p=0.407)
CVAEs: 9% risperidone (5 stroke, 1 TIA) vs 1.8% placebo.
2 deaths from stroke in risperidone group.
Katz, 1999
US (FAIR)
Katz, 2004 (subanalysis)
Grossman, 2004 (subanalysis)
62512 weeksDouble-blind, multicenterAge 55 or older, residing in a nursing home or chronic disease hospital, DSM-IV diagnosis of Alzheimer's disease, vascular dementia, or a combination of the two, with scores of 4 or greater on the Functional Assessment Staging rating scale and 23 or lower on the MMSE. Total score of 8 or more and a global rating of 1 or more on BEHAVE-AD rating scale.Untreated reversible causes of dementia, medical or neurological conditions that diminish cognition, diagnosis of dementia related to infection with HIV or substance-induced persistent dementia, diagnosis of delirium or amnestic disorder, and psychiatric diagnosis that could have accounted for the observed psychotic disturbances.risperidone 0.5 mg, 1 mg, or 2 mg per day.
Doses for patients receiving 1 mg and 1 mg were adjusted during the first week in increments of 0.5 mg every 2 days.
Single-blind placebo washout of 3 to 7 days.Use of antipsychotics, antidepressants, or mood stabilizers not allowed.
Benztropine allowed to treat EPS.
Lorazepam (up to 3 mg/day for up to 4 days in any 7-day period) could be given until the end of week 4. Use of chloral hydrate for insomnia was allowed at the lowest effective dose.
Mean age 82.7 (sd 7.7)
68% female
89% white, 11% multiracial
73% Alzheimer's dementia
16% vascular dementia
12% mixed
729 screened/625 eligible/625 enrolled190/NR/617 analyzedBEHAVE-AD, CMAI, CGIAssessments at selection, baseline, and weeks 1–4, 6, 8, 10, and 12 (or when patient was terminated from treatment).
Elicited from patients' primary caregivers by specifically trained raters.
Mean change from baseline to endpoint, risperidone vs placebo (p vs placebo):
BEHAVE-AD (Total)
0.5 mg -4.8 (p.37); 1 mg -6.5 (p=0.002); 2 mg -6.4(p=0.001); placebo -4.2
BEHAVE-AD (Psychosis subscale)
0.5 mg -1.6 (p=0.68); 1 mg -2.5 (p=0.005); 2 mg -2.2 (p=0.01); placebo -1.5
BEHAVE-AD (Aggressiveness subscale)
0.5 mg -1.3 (p=0.11); 1 mg -1.7 (p=0.002); 2 mg -2.4 (p<0.001); placebo -0.9
Information regarding adverse events was obtained at each visit, Extrapyramidal Symptom Rating Scale.Withdrawals due to adverse events:
8% risperidone 0.5 mg
16% risperidone 1 mg
24% risperidone 2 mg
12% placebo
Change from baseline to endpoint, Extrapyramidal Symptom Rating Scale scores (total and hypokinesia scales):
risperidone 0.5 mg: −0.48 and 0.01 (NS vs placebo)
risperidone 1 mg: 0.84 and 0.95 (NS vs placebo)
risperidone 2 mg: 2.37 and 2.01 (p<0.001 vs placebo for both scales)
placebo: −0.22 and 0.17
Tardive dyskinesia emerged in 1 placebo patient, 0 risperidone
Deaths:
4% risperidone 0.5 mg; 9% risperidone 1 mg; 4% risperidone 2 mg; 3% placebo
Serious adverse events:
11% risperidone 0.5 mg; 16% risperidone 1 mg; 18% risperidone 2 mg; 13% placebo
Mintzer, 2006
US (FAIR)
4738 weeksDouble-blind, multicenterAge 55 or older, with Alzheimer's disease, residents of nursing home s or long-term care facilities, and mobile (ambulatory, walked with assistance, or used a wheelchair independently). Met criteria for psychosis of Alzheimer's disease and were deemed to be in need of treatment with an atypical antipsychotic in accordance with OBRA guidelines. Scored 2 or higher on any item of the BEHAVE-AD Psychosis subscale and between 5 to 23 on a MMSE.Patients excluded had recently been treated with neuroleptic injections, had other medical conditions that diminish cognition, or had other psychiatric disorders that produce psychotic symptoms. Patients with epilepsy, recent diagnoses or cancer (except nonmelanoma skin cancers), unstable medical conditions, changes in prescription medications 30 days before screening, or significant baseline laboratory or ECG abnormalities were also excluded.Risperidone daily flexible dosage in 2 divided doses. Initiated at 0.50 mg and increased after 3 days to 1 mg. If inadequate clinical response by day 13, increased to 1.5 mg. Subsequent adjustments were allowed in patients who experienced adverse events. Minimum treatment dosage was 0.5 mg daily.One-week placebo run-in to wash out previously used psychotropic medications. Run-in length reduced for patients not using psychotropic medications and those whose psychosis or agitation worsened.Lorazepam (maximum daily dose 1.0 mg) during the run-in phase and the first 4 weeks of treatment.
Maximum daily dose of 0.5 mg 3 days per week.
Mean age 83.3 77% female 80.1% white, 10.1% black, 6.6% Hispanic, 2.1% Asian, 1.1% other100% Alzheimer's dementia560/NR/473117/1/416BEHAVE-AD Psychosis (primary efficacy measure)
CGI-C
BEHAVE-AD: Activity disturbances, Aggressiveness, Diurnal rhythm disturbances, Affective disturbance, Anxieties and phobias, Total, Global Part 2.
BEHAVE-AD assessed at baseline and treatment weeks 1, 2, 4, and 8.
CGI-Change determined at weeks 1, 2, 3, 4, 6, and 8, using baseline CGI-S as a reference point.
N=416
Mean change from baseline to endpoint (SD), risperidone vs placebo (analysis of covariance model, including treatment group and site as factors and baseline score as a covariate):
BEHAVE-AD (Psychosis): −2.9 (3.55) vs −2.3 (3.55) p=0.118
BEHAVE-AD (Activity disturbances): −0.4 (1.78) vs −0.6 (1.80) p=0.812
BEHAVE-AD (Aggressiveness): −1.1 (2.42) vs −1.0 (2.83) p=0.078
BEHAVE-AD (Diurnal rhythm disturbances): −0.2 (0.81) vs −0.2 (3.55) p=0.643
BEHAVE-AD (Affective disturbance): −0.1 (1.19) vs −0.2 (1.11) p=0.199
BEHAVE-AD (Anxieties and phobias): −0.4 (1.67) vs −0.4 (1.49) p=0.943
BEHAVE-AD (Total): −4.9 (8.23) vs −5.0 (8.27) p=0.386
BEHAVE-AD (Global Part 2): −0.6 (0.91) vs −0.5 (0.97) p=0.111
CGI-C, risperidone vs placebo (controlling for site)
Marked worsening: 4.0% vs 4.2%
Moderate worsening: 6.0% vs 4.2%
Minimal worsening: 5.5% vs 5.6%
No change: 18.9% vs 30.0%
Minimal improvement: 33.3% vs 21.6%
Moderate improvement: 24.9% vs 23.0%
Marked improvement: 7.5% vs 11.3%
overall p=0.416
Simpson-Angus Scale, Barnes Akathisia Scale, AIMSWithdrawals due to adverse events:
quetiapine 200 mg: 12%
quetiapine 100 mg: 7.3%
placebo: 35%: 7.6%
No significant difference in mean changes on SAS and AIMS among treatment groups (data not reported)
Incidence of EPS-related adverse events:
quetiapine 200 mg: 5%
quetiapine 100 mg: 5%
placebo: 4%
Mean change in MMSE at end of treatment was 0 for all treatment groups.
1 transient ischemic attack in placebo group.
Aripiprazole
Mintzer, 2007
Multinational
48710 weeksDouble-blind, multicenterMen and women aged 55–95 years (inclusive), who were diagnosed with AD and psychotic symptoms of delusions or hallucinations, who were living in nursing homes or residential assisted-living facilities for a minimum of four weeks ; capable of selflocomotion (alone or with the aid of an assistive device) and have an identified or proxy caregiver. MMSE score2 of 6–22 points (inclusive), and had experienced persistent or intermittent delusions, hallucinations or both for at least one month; presence of psychotic symptoms was confirmed by scores of 6 or higher on either the delusions or hallucinations items of the NPI-NH Psychosis Subscale score.an axis I diagnosis of delirium, amnestic disorder, bipolar disorder, schizophrenia or schizoaffective disorder, or mood disorder with psychotic features; non-AD; a current major depressive episode with psychotic symptoms of hallucinations or delusions; seizure disorders; history of refractoriness to antipsychotics; known hypersensitivity to aripiprazole or other quinolinones; suicidal ideation or history; unstable thyroid function; clinically significant abnormal laboratory findings; or previous participation in aripiprazole trials; were women who were pregnant or nursing or of childbearing potential and not using adequate contraception.fixed doses of aripiprazole (2 mg/day, 5 mg/day, or 10 mg/day) or placebo for 10 weeks7 day washout and 28 day screening periodLorazepam and anticholinergic medication for treating EPS, at a maximum dose equivalent to 2 mg/day of benztropine, stable doses of cholinesterase inhibitors or antidepressants at baselineMean age 82.5
79% female
87% white
100% Alzheimer’s DiseaseNR/NR/654203/NR/475NPI-NH Total score and subscores Clinical Global Impression–Severity of Illness (CGI-S) score; BPRS Psychosis Subscale, Core and Total scores; CMAI Total score; MMSE score; and the mean CGI-I scoreNPI-NH administered by caregiver, all others by investigators NPI-NH and CGI-S were performed at randomization (baseline), and at weeks 1, 2, 3, 4, 6, 8, and 10, CGI-I evaluations were performed at each time point except baseline.
The BPRS and CMAI baseline, then every 2 weeks during the study. MMSE was carried out at screening and week 10.
Placebo vs. Aripiprazole 2 mg vs Aripiprazole 5 mg vs. Aripiprazole 10 mg
NPI-NH total mean change [2 x SD] 13.0 [32.8] vs. 14.1 [38.6] vs. 15.9 [37.2] vs 17.6[33.2]
CGI-S mean change [2 x SD] 0.5 [1.6] vs. 0.5 [1.8] vs. 0.6 [1.8] vs. 0.7 [1.8]
CGI-I (SD) 3.5 [2.8] vs. 3.3 [2.6] vs. 3.2 [2.8] vs. 3.2 [3.0]
MMSE mean change [2 x SD] 0.9 [6.2] vs. 0.3 [6.2] vs. 1.6 [7.0] vs. 1.0 [7.4]
Medical review of adverse event reports, physical examination, vital sign measurements, and results of standard clinical laboratory tests and 12-lead electrocardiograms (ECGs). Extrapyramidal symptoms (EPS) were rated using the Simpson–Angus Scale, the Abnormal
Involuntary
Movement Scale and the Barnes Akathisia
Rating Scale
Placebo vs. Aripiprazole 2 mg vs Aripiprazole 5 mg vs. Aripiprazole 10 mg n(%)
Accidental injury 23 (19) vs. 35 (30) vs. 29 (24) vs. 25 (20)
Agitation 20 (17) vs. 13 (11) vs. 9 (7) vs. 13 (11)
Urinary-tract infection 16 (13) vs. 19 (16) vs. 23 (19) vs. 25 (20)
Anorexia 13 (11) vs. 10 (9) vs. 6 (5) vs 7 (6)
Ecchymosis 12 (10) vs. 10 (9) vs. 6 (5) vs. 11 (9)
Edema, peripheral 10 (8) vs. 12 (10) vs. 7 (6) vs. 11 (9)
Insomnia 10 (8) vs. 11 (9) vs. 7 (6) vs. 6 (5)
Rash 10 (8) vs. 11 (9) vs. 11 (9) vs. 10 (8)
Vomiting 8 (7) vs. 13 (11) vs. 11 (9) vs. 8 (7)
Extremity pain 7 (6) vs. 8 (7) vs. 11 (9) vs. 12 (10)
Skin ulcer 9 (8) vs. 12 (10) vs. 14 (12) vs. 11 (9)
Diarrhea 7 (6) vs. 7 (6) vs. 8 (7) vs. 11 (9)
Constipation 6 (5) vs. 6 (5) vs. 6 (5) vs. 4 (3)
Coughing 6 (5) vs. 6 (5) vs. 4 (3) vs. 7 (6)
Upper respiratory infection 6 (5) vs. 10 (9) vs. 6 (5) vs. 6 (5)
Infection 5 (4) vs. 9 (8) vs. 6 (5) vs. 7 (6)
Confusion 5 (4) vs. 3 (3) vs. 9 (7) vs. 6 (5)
Headache 4 (3) vs. 5 (4) vs. 5 (4) vs. 9 (7)
Back pain 4 (3) vs. 6 (5) vs. 4 (3) vs. 8 (7)
Abdominal pain 4 (3) vs. 3 (3) vs. 8 (7) vs. 5 (4)
Weight loss 4 (3) vs. 6 (5) vs. 6 (5) vs. 5 (4)
Somnolence 4 (3) vs. 4 (3) vs. 12 (10) vs. 9 (7)
Asthenia 3 (3) vs. 7 (6) vs. 11 (9) vs. 12 (10)
Conjunctivitis 3 (3) vs. 7 (6) vs. 3 (2) vs. 3 (2)
Urinary incontinence 2 (2) vs. 2 (2) vs. 12 (10) vs. 7 (6)
Edema 2 (2) vs. 6 (5) vs. 4 (3) vs. 2 (2)
Abnormal gait 1 (1) vs. 2 (2) vs. 9 (7) vs. 5 (4)
Increased salivation 1 (1) vs. 2 (2) vs. 9 (7) vs. 2 (2)
Lightheadedness 0 (0) vs. 6 (5) vs. 5 (4) vs. 4 (3)
Cerebrovascular adverse events were reported for seven aripiprazole-treated patients during the study period (one in the 2 mg/day dose group, two in the 5 mg/day dose group and four in the 10 mg/day dose group), compared with no patients in the placebo group.
EPS-related adverse events placebo, 6%; aripiprazole 2 mg/day, 8%; aripiprazole 5 mg/day, 7%; aripiprazole 10 mg/day, 7%).
De Deyn, 2005
Multinational
20810 weeksDouble-blind, multicenterNoninstitutionalized men and women, aged 55–95 years, diagnosed with AD, and with symptoms of delusions or hallucinations present (at least intermittently) for 1 month or longer were eligible for enrollment in the study. MMSE score of 6–24, and a score of 6 on the delusions or hallucinations items of the Neuropsychiatric Inventory (NPI)20 assessment at baseline.diagnosis of delirium, amnesic disorders, bipolar disorder, schizophrenia or schizoaffective disorder, or mood disorder with psychotic features; psychotic symptoms better accounted for by another general medical condition or direct physiologic effects of a substance (eg, medication);
refractory to neuroleptics used to treat psychotic symptoms in the past.
Aripiprazole 2 mg/d (Aripiprazole could be titrated to higher doses (5, 10, and 15 mg/d) at 2-week intervals) or placebo, administered once-daily for 10 weeks,7-day washout period for previous psychotropic medicationZolpidem, anti-depressants, lorazepam, anticholinergic treatment of EPSMean age 81.5
72% female
98% white
100% Alzheimer’s DiseaseNR/NR/20831/NR/208NPI-NH Total score and subscores Clinical Global Impression–Severity of Illness (CGI-S) score; BPRS, Core and Total scores; CMAI Total score; MMSE score;NPI-NH administered by caregiver, others NR. Timing of assessments every two weeks following baseline.Placebo vs. aripiprazole
NPI Psychosis mean change 5.52 vs. 6.55 P = 0.169
NPI Total mean change 9.75 vs. 11.20 P = 0.582
BPRS Psychosis mean change 1.27 vs. 1.93 P = 0.029
BPRS Core mean change 2.7 vs. 3.9 P = 0.042
BPRS Total mean change 6.58 vs. 8.53 P = 0.153
CGI-S mean change 0.54 vs. 0.69 P = 0.345
CGI-I 3.07 vs. 3.17 P = 0.564
MMSE mean change 0.53 vs. 0.81 P = 0.001
AE reports, extrapyramidal symptoms (EPS) rating scales, 12-lead ECGs, vital signs, and body weight measurements.Serious AEs were reported by 25 patients (12%) during double-blind treatment or within 30 days of discontinuation (placebo, n = 9; aripiprazole, n = 16)
EPS-related AEs (aripiprazole, n = 5; placebo, n = 4).
Weight changes aripiprazole and placebo (+0.17 kg vs. 0.33 kg; P = 0.321), and clinically significant gain ( 7% increase in weight from baseline) at end point (aripiprazole, 5%; placebo, 3%; P = 0.695).
Streim 2008
United States
25610 weeksDB RCT
Multicenter
Men and women aged 55–95 years, diagnosed with AD (DSM–IV criteria), and who had psychotic symptoms of delusions or hallucinations for 1 month, institutionalized for 4 weeks before study entry; capable of self-locomotion or locomotion with the aid of an assistive device; and have a caregiver or family member who could serve as a collateral informant for study assessments and, if necessary, provide proxy consent to participate. MMSE score between 6 and 22 at screening, and a score of 6 on either the delusions or hallucinations items of the Neuropsychiatric Inventory–Nursing Home Version (NPI-NH) at baseline (at the time of randomization).Axis I diagnosis of delirium or schizophrenia; a schizoaffective, mood, bipolar, or amnestic disorder; any reversible cause of dementia; continuous symptoms of psychosis before the onset of dementia; psychotic symptoms better accounted for by another medical condition or direct effects of a substance; a current episode of major depression with symptoms of psychosis; dementia resulting from vascular causes; any specific non-AD-type dementia caused by trauma, disease, infection, or substance abuse; a seizure disorder; and/or unstable thyroid pathology within the past 3 months; previously been refractory to antipsychotic drug treatment for psychosis; had been randomized in an aripiprazole clinical study; had participated in any clinical study with an investigational agent 1 month; recent treatment with a long-acting antipsychotic agent in which the last dose was administered 1 full cycle plus 1 week prior to randomization; met DSM–IV criteria for any significant substance use disorder; were deemed to be at significant risk of suicide; were likely to require prohibited concomitant therapy; were known to be allergic or hypersensitive to aripiprazole or quinolinones; had any laboratory test, vital sign, or ECG abnormalities that could indicate an elevated risk for significant adverse events (AEs), or any medical condition that would make study participation unsafe.Placebo vs. Aripiprazole (2–15 mg, mean of 10 mg) for 10 weeks (there was early escape at 6 weeks)7 day washouttrazodone 25–50 mg, zolpidem
2.5–5.0 mg or temazepam 7.5–15.0 mg analgesics or antipyretics, anxiolytics, cognition enhancers, and selective serotonin reuptake inhibitors
Mean age 83.0
24% male
89% white
83% delusionalNR/NR/330105/0/249NPI. CGI-S, CGI-I, BPRS, CMAI, CDS, MMSENPI-NH and CGI-S assessments were performed at randomization (baseline) and Weeks 1, 2, 3,4, 6, 8, and 10; CGI-I was evaluated at each time point except baseline. BPRS and CMAI were assessed at baseline, then every 2 weeks during the study. The Cornell depression scale was assessed at baseline and Weeks 6 and 10.
MMSE was evaluated at screening and Week 10.
Placebo vs.. Aripiprazole (2*SD)
NPI-NH Psychosis −4.62 (9.56) vs. −4.53 (9.23) P = 0.883
CGI-S 0.43 (1.65) vs. −0.57 (1.63) P = 0.198
NPI-NH total −10.01(37.66) vs. −16.43 (34.63) P = 0.009
BPRS Total − 5.14 (17.76) vs. − 7.73 (16.32) P = 0.031
BPRS Psychosis − 1.24 (3.91) vs − 1.18 (3.63) P = 0.823
BPRS Core − 1.97 (6.80) vs. − 2.48 (5.58) P = 0.231
CMAIa − 6.16 (29.11) vs. − 10.25 (25.70) P = 0.030
Cornell scale − 0.13 (10.18) vs. − 1.98 (8.25) P = 0.006
NPI-NH Total Caregiver distress − 4.31 (14.37) vs. − 7.23 (14.64) P = 0.003
NPI-NH Psychosis Caregiver distress − 1.62 (3.27) vs. − 1.89 (3.63) P = 0.246
MMSE − 0.57 (6.34) vs. − 0.77 (5.97) P = 0.685
ADCS-ADL-SEV − 0.22 (9.03) vs. − 0.83 (9.88) P = 0.442

CGI-I score at endpoint 3.65 (2.64) vs. 3.13 (2.35) P = 0.002
NPI-NH Total response 28% vs. 46% P = 0.006
NPI-NH Psychosis response 52% vs. 54% P = 0.959
Medical review of AE reports, physical examination, vital sign measurements, standard clinical laboratory tests, and 12-lead ECGs. Extrapyramidal symptoms (EPS) were evaluated using the Simpson–Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS) and Barnes Akathisia Rating Scale (BAS).Placebo vs.. Aripiprazole (%)
Accidental injury 30 vs. 21
Agitation 12 vs. 8
Asthenia 7 vs. 12
Ecchymosis 13 vs. 12
Rash 12 vs. 10
Somnolence 4 vs. 14
Ulcer skin 12 vs. 9
Urinary tract infection 11 vs. 14
Vomiting 8 vs. 10
EPS-related AEs 4 vs. 5
Intramuscular Aripiprazole
Rappaport 2009
USA
12924 hoursDouble-blind, multicenterMale and female patients (aged 55 to 95) diagnosed with AD, vascular, or mixed dementia, residing in healthcare facilities) who manifested moderate-to severe acute exacerbations of agitated behaviors defined as Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) score ≥ 15 and ≤ 32 with at least 1 of the 5 items with a score 4 or more.Other major DSM-IV Axis I psychiatric disorders; those with a history of neuroleptic malignant syndrome, seizure, abnormal electroencephalogram not attributable to AD or vascular dementia, severe head trauma or stroke, and compulsorily detained patients.Injection of IM aripiprazole (2.5, 5 or 10 mg) or IM placebo, followed by a second injection 2 hours later (2.5, 5 mg or placebo). Patients were clinically observed over 24 hours.NRYes except medications that might have interfered with assessments of efficacy or safety were prohibited within 4 hours before baseline assessment and during the 4-hour efficacy evaluation phase after baseline.Placebo vs. aripiprazole
n = 26 vs. 103
% male 38 vs.35
% white 85 vs. 81
% black 25 vs. 19
% Hispanic 6 vs. 10
Placebo vs. aripiprazole
Underlying diagnosis
%
Alzheimer's 85 vs.78
Mixed 8 vs. 15
Vascular 8 vs. 8
NR/NR/1502/0/127PEC, Agitation–Calmness Evaluation Scale (ACES), Clinical Global Impressions–Severity of Illness (CGI-S), and Clinical Global Impressions–Improvement (CGI-I)Assessed at baseline 30 minutes, 1 hour, 1.5 hours, 2, 3, 4, 6, 12, 24 hoursACES increase from baseline
Placebo vs. all aripiprazole
0.8 (0.1) vs.. 1.3 (0.1)
All other comparisons are in graphs
AEs and changes in electrocardiograms, vital signs, laboratory tests, and the Simpson Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Mini Mental State Examination (MMSE)Placebo vs. All aripiprazole n(%)
Any AE 8 (32.0) vs. 56 (54.4)
Somnolence 2 (8.0) vs. 37 (35.9)
Dementia 0 vs. 3 (2.9)
Lethargy 0 vs. 1 (1.0)
Vomiting 0 vs. 4 (3.9)
Pyrexia 0 vs. 1 (1.0)
Skin laceration 2 (8.0) vs. 2 (1.9)
Fall 1 (4.0) vs. 1 (1.0)
Femoral neck fracture 0 vs. 1 (1.0)
Electrocardiogram change 0 vs. 1 (1.0)
Irregular heart rate 0 vs. 1 (1.0)
Insomnia 0 vs. 3 (2.9)
Agitation 2 (8.0) vs. 1 (1.0)

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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