Evidence Table 3. KQ3: Efficacy or effectiveness of antidepressants for treating depression and its accompanying symptoms

Study CharacteristicsResearch ObjectiveInclusion/ExclusionBaseline CharacteristicsHealth Outcome ResultsAdverse Events (%)Analysis and Quality Rating
Duration
Study Design
Author: Research objective: Inclusion criteria: Mean age (yrs): Anxiety outcomes: Overall adverse events: Overall attrition rate:
Baldwin et al., 1996To compare efficacy of NEF and PAR for treatment of moderate-severe major depression
  • Adults 18 or older
  • Outpatients
  • MDD according to DSM-III-R
  • Minimum HAM-D-17 score of 18
  • Rated at least moderately ill on CGI-S
D1: 38.3Improvement in HAM-A score was 6.5 for NEF vs. 8.0 for PAR (95% CI for diff between groups: -0.7 to 3.8) D1: 8423.1%
Country and setting: Duration of study: Exclusion criteria: D2: 37.9 D2: 78 ITT Analysis:
Europe, multicenter (20 psychiatric clinics)8 wks
  • Additional mental illnesses or organic mental disorder
  • Concomitant psychotherapeutic medications
  • ECT within 6 mos
  • Substance abuse or dependence (within 1 yr)
  • Clinically sig medical disease
  • Pregnant or lactating
  • Suicidal (serious risk)
  • Lack of response of current MDD episode to 2 prior courses of therapy
Sex (% female): Dizziness: Yes
Funding: Study design: D1: 60 D1: 17 Quality rating:
Bristol-Myers SquibbRCT D2: 50 D2: 9Fair
Overall study N: Race (% white): Headache:
206 randomized; 196 included in analysis D1: NR D1: 35
Intervention: D2: NR D2: 25
D1: Nefazodone 200–600 mg/d (mean 472) Baseline HAM-D-17: Nausea:
D2: Paroxetine 20–40 mg/d (mean 32.7) D1: 24.6 D1: 27
D2: 24.8 D2: 30
Baseline HAM-A: Somnolence:
D1: 19 D1: 16
D2: 18.3 D2: 24
Author: Research objective: Inclusion criteria: Mean age (yrs): Sleep outcomes Diarrhea: Overall attrition rate:
Beasley et al., 1991To compare FLUO and TRA for treatment of major depression and to evaluate activation and sedation effects
  • Adults 18 or older
  • Outpatients
  • MDD according to DSM-III
  • Minimum HAM-D-21 score of 20
  • Duration at least 4 wks
D1: 40.0Improvement in HAM-D Sleep Disturbance Factor was 1.6 points in FLUO-treated group vs. 2.7 points in TRA group (P = 0.001) D1: 7.734.1%
Country and setting: Duration of study: Exclusion criteria: D2: 40.0 D2: 3.3 ITT Analysis:
United States, multicenter (3 sites)6 wks
  • Additional mental illnesses or organic mental disorder
  • Concomitant psychotherapeutic medications
  • Substance abuse (within one yr)
  • Placebo response during lead-in
Sex (% female): Dizziness: Yes
Funding: Study design: D1: 64.6 D1: 6.2 Quality rating:
Eli Lilly and CompanyRCT D2: 68.8 D2: 21.3Fair
Overall study N: Race (% white): Headache:
126 randomized; 120 included in analysis D1: 98.5 D1: 21.5
Intervention: D2: 98.4 D2: 27.9
D1: Fluoxetine 20–40 mg/d (median 20 mg/d) Baseline HAM-D-21: Insomnia:
D2: Trazodone 50–400 mg/d (median 250 mg/d) D1: 23.4 (2.7) D1: 9.2
D2: 24.3 (3.6) D2: 3.3
Baseline HAM-D Sleep Factor: Nausea:
D1: 3.8 (1.7) D1: 27.7
D2: 3.8 (1.8) D2: 24.6
Baseline HAM-A: Somnolence:
NR D1: 20.0
D2: 45.9
Sweating (increase):
D1: 4.6
D2: 0
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in patients with pain: Cardiovascular adverse events (high systolic BP): Overall attrition rate:
Brannan et al., 2005To evaluate efficacy of DUL for treatment of pain and depression in patients with major depression and painful physical symptoms
  • Adults 18 or older
  • Outpatients
  • MDD according to DSM-IV
  • Minimum HAM-D-17 score of 15
  • CGI-S of 4 or more
  • BPI average pain score of 2 or more
D1: 40.8Mean HAM-D-17 improvement was similar for both groups (-10.9 for DUL vs. -10.3 for placebo, P = 0.544). Response rates were similar for DUL and placebo (42% vs. 40%, P = 0.901). Remission rates were also similar (23% vs. 24%, P = 0.887) D1: 4.1NR
Country and setting: Duration of study: Exclusion criteria: D2: 40.3 Pain outcomes: D2: 4.1 ITT Analysis
United States, multicenter (25 psychiatry clinics)7 wks
  • Additional mental illness or organic mental disorder
  • Substance abuse or dependence
  • Clinically sig medical disease
  • Suicidal (serious risk)
  • Primary pain disorder with diagnosis such as arthritis, migraine, or fibromyalgia
  • Treatment resistant depression or lack of response of current MDD episode to 2 prior courses of therapy
Sex (% female): Mean reduction in BPI average pain was 2.32 (0.21) for DUL-treated patients compared to 1.80 (0.20) for those receiving placebo (P = 0.066). Mean changes in BPI worst pain, least pain, and current pain did not differ between groups (P > 0.10 for all). Mean changes in VAS overall pain did not differ between groups (values NR and P = NR) (high diastolic BP): Yes
Funding: Study design: D1: 68.1 D1: 1.6 Quality rating:
Eli Lilly and CompanyRCT D2: 62.4 D2: 5.5Fair
Overall study N: Race (% white): Changes in weight (decrease):
282 randomized; 268 included in analysis D1: 81.6 D1: 7.1
Intervention: D2: 79.4 D2: 0.7
D1: Duloxetine 60 mg/d Baseline HAM-D-17: Constipation:
D2: Placebo D1: 23.4 (3.5) D1: 9.2
D2: 22.4 (3.4) D2: 6.4
BPI average pain: Diarrhea:
D1: 4.85 (1.69) D1: 17.7
D2: 4.62 (1.54) D2: 10.6
Baseline 100mm VAS (overall pain): Dizziness:
D1: 49.8 (22.2) D1: 9.9
D2: 46.8 (19.7) D2: 5.7
Baseline HAM-A: Headache:
NR D1: 14.2
D2: 13.5
Insomnia:
D1: 10.6
D2: 6.4
Nausea:
D1: 39.7
D2: 9.9
Fatigue:
D1: 16.3
D2: 1.4
Author: Research objective: Inclusion criteria: Mean age (yrs): Anxiety outcomes Changes in weight (decrease): Overall attrition rate:
Chouinard et al., 1999To evaluate antidepressant and anxiolytic efficacy of FLUO and PAR in patients with major depression
  • Outpatients
  • MDD according to DSM-III-R
  • Minimum HAM-D-21 score of 20 and score of 2 on HAM-D item 1
  • Depression symptoms for at least 1 mo
D1: 41.2Improvements in Covi Anxiety Scale, State-Trait Anxiety Inventory, and HAM-D Anxiety/Somatization Factor were similar in 2 treatment groups (scores NR; P = NR) D1: 11.936%
Country and setting: Duration of study: Exclusion criteria: D2: 40.6Mean improvement from baseline in HAM-D Psychic Anxiety item was 1.21 for FLUO and 1.17 for PAR (P = 0.823). Improvement from baseline in HAM-D Agitation item was 0.39 for FLUO and 0.40 for PAR (P = 0.978) D2: 2.9 ITT Analysis:
Canada, multicenter (8 sites)12 wks
  • Additional mental illnesses or organic mental disorder
  • Concomitant or recent psychotherapeutic drugs
  • ECT within 2 mos
  • Concurrent formal psychotherapy
  • Illicit drug or alcohol abuse (past or present)
  • Suicidal (sig risk)
  • Pregnant or lactating
  • Clinically sig medical disease
Sex (% female): (increase): Yes
Funding: Study design: D1: 59.4 D1: 13.9 Quality rating:
SmithKline BeechamRCT D2: 63.7 D2: 10.8Fair
Overall study N: Race (% white): Constipation:
203 randomized; 198 included in analysis D1: 98.0 D1: 4.0
Intervention: D2: 95.1 D2: 17.7
D1: Fluoxetine 20–80 mg/d (mean 27.5) Baseline HAM-D-21: Diarrhea:
D2: Paroxetine 20–50 mg/d (mean 25.5) D1: 25.45 (0.46) D1: 18.8
D2: 25.91 (0.46) D2: 11.8
Baseline HAM-A: Headache:
NR D1: 36.6
D2: 36.3
Insomnia:
D1: 22.8
D2: 26.5
Nausea:
D1: 31.7
D2: 37.3
Sexual dysfunction:
D1: 7.3 of males
D2: 10.8 of males
Somnolence:
D1: 16.8
D2: 18.6
Suicidality:
D1: 2.0
D2: 2.0
Sweating (increase):
D1: 5.9
D2: 13.7
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in patients with melancholia: Headache: Overall attrition rate:
Clerc et al., 1994To compare efficacy and short-term safety of VEN and FLUO in hospitalized patients with MDD and melancholia
  • Adults 18 or older
  • Hospitalized patients
  • MDD with melancholia according to DSM-III-R
  • Depression duration at least 1 mo
  • MADRS at least 25
D1: 53.6Mean decrease in HAM-D score was sig better for VEN (-18) compared to FLUO (-12.4) (P = 0.027) D1: 923%
Country and setting: Duration of study: Exclusion criteria: D2: 49.0HAM-D response rates were 73% in VEN-treated group compared to 50% in FLUO-treated group. Diff not statistically sig (P = NR) D2: 3 ITT Analysis
France and Belgium, multicenter (hospitals)6 wks
  • Clinically sig medical disease
  • Concurrent ECT
  • Concurrent psychotherapy
Sex (% female): Insomnia: Yes
Funding: Study design: NR D1: 9 Quality rating:
Wyeth-AyerstRCT Race (% white): D2: 9Poor
Overall study N: NR Nausea: High differential attrition
68 Baseline HAM-D-21: D1: 12
Intervention: D1: 29.7 (4.2) D2: 9
D1: Fluoxetine 40 mg/d D2: 29.1 (5.2)
D2: Venlafaxine 200 mg/d Baseline HAM-A:
NR
Author: Research objective: Inclusion criteria: Mean age (yrs): Sleep outcomes Constipation: Overall attrition rate:
Cunningham et al., 1994To compare efficacy and safety of TRA, VEN, and placebo in outpatients with major depression
  • Adults 18 or older
  • Outpatients
  • MDD according to DSM-III-R
  • Minimum HAM-D-21 score of 20
  • Depression duration at least 1 mo
Overall: 40.7HAM-D Sleep Factor scores at endpoint were sig better for TRA (1.42) than for VEN (2.22; P < 0.05) and placebo (1.95; P < 0.05) D1: 933.78%
Country and setting: Duration of study: Exclusion criteria: Sex (% female): D2: 22 ITT Analysis:
United States and Canada, multicenter (6 sites)6 wks
  • Additional mental illnesses or organic mental disorder
  • Concomitant or recent psychotherapeutic drugs
  • Drug or alcohol dependence (within 2 yrs)
  • ECT within 14 days
  • Investigational drug use within 2 yrs
  • Suicidal (serious risk)
  • Pregnant, lactating, or child-bearing potential without contraception
  • Unstable medical disease
  • History of seizure disorder
  • Placebo response during washout (20% improvement on HAM-D)
NR D3: 4Yes
Funding: Study design: Race (% white): Dizziness: Quality rating:
Wyeth-AyerstRCTNR D1: 36Fair
Overall study N: Baseline HAM-D-21: D2: 17
227 randomized; 225 included in analysis D1: 24.66 D3: 5
Intervention: D2: 25.02 Nausea:
D1: Trazodone 150–400 mg/d D3: 24.41 D1: 19
D2: Venlafaxine 75–200 mg/d Baseline HAM-D Sleep Factor: D2: 44
D3: Placebo D1: 3.60 D3: 5
D2: 3.52 Somnolence:
D3: 3.20 D1: 61
Baseline HAM-A: D2: 43
NR D3: 12
Sweating (increase):
D1: 3
D2: 12
D3: 1
Author: Research objective: Inclusion criteria: Mean age (yrs): Response and remission rates did not differ sig among DUL 120 mg (71%; 52%), DUL 80 mg (65%; 46%) and PAR (74%; 44%) (P = NR) Headache: Overall attrition rate:
Detke, 2004To determine comparative efficacy and safety of DUL and PAR for treatment of MDD
  • Adults 18 or older
  • Met DSM-IV and MINI criteria for MDD
  • CGI-S rating > 4
  • Diagnosed with MDD according to DSM-III or -IV
  • Minimum HAM-D score of 15
D1: 43.1PGI scores were sig superior in patients receiving PAR than patients receiving 80 mg/d DUL (P < 0.05) D1: 5.313.3%
Country and setting: Duration of study: Exclusion criteria: D2: 44.7Improvments in pain scores similar between active medications: DUL 80 mg and placebo (P = 0.063), DUL 120 mg and placebo (P = 0.086). Improvement in pain was superior to placebo (P = 0.035) D2: 5.4 ITT analysis:
United States Multicenter, university clinics8 wks
  • Pregnant
  • Additional mental illnesses or organic mental disorder
  • Illicit drug and alcohol abuse
  • Clinically sig medical disease
  • Suicidal tendencies
D3: 42.0 D3: 4.7Yes
Funding: Study design: D4: 42.0 Nausea: Quality rating:
Eli LillyRCT Sex (% female): D1: 12.6Fair
Overall study N: D1: 70 D2: 5.4
367 D2: 70 D3: 11.6
Intervention: D3: 58 Somnolence (fatigue):
D1: Duloxetine 80 mg/d D4: 58 D1: 2.1
D2: Duloxetine 120 mg/d Race (% white): D2: 7.5
D3: Paroxetine: 20 mg/d D1: 95 D3: 5.8
D4: placebo D2: 92 Sweating (increase):
D3: 86 D1: 4.2
D4: 86 D2: 8.6
Baseline (HAM-A): D3: 5.8
D1: 17.8
D2: 18.0
D3: 18.5
D4: 17.9
Mean HAM-D score at baseline:
D1: 19.9 (3.6)
D2: 20.2 (3.4)
D3: 20.3 (4.1)
D4: 19.9
Author: Research objective: Inclusion criteria: Mean age (yrs): Pain outcomes: Cardiovascular adverse events (new hypertension): Overall attrition rate:
Detke et al., 2002To evaluate efficacy of DUL vs. placebo for treatment of MDD and associated painful symptoms
  • Adults 18 or older
  • MDD according to DSM-IV
  • Minimum HAM-D-17 score of 15
  • Other: CGI-S of 4 or more
D1: 42.44Mean reduction in 100mm VAS for overall pain was statistically sig greater for duloxetine (~8.5 mm) compared to placebo (~2.5 mm) (Mean change estimated from figure; P = 0.019) D1: 0.8NR
Country and setting: Duration of study: Note: Painful symptoms not required for inclusion D2: 42.34 D2: 0 ITT Analysis
United States, multicenter (18 sites)9 wks Exclusion criteria: Sex (% female): Constipation: Yes
Funding: Study design:
  • Additional mental illness or organic mental disorder
  • Psychotherapy within 6 wks
  • Substance abuse or dependence (within 1 yr)
  • Clinically sig medical disease
  • Treatment resistant depression or lack of response of current MDD episode to 2 prior courses of therapy
D1: 65.0 D1: 13 Quality rating:
Eli Lilly and CompanyRCT D2: 68.0 D2: 1.6Fair
Overall study N: Race (% white): Diarrhea:
245 D1: 87.0 D1: 18.7
Intervention: D2: 84.4 D2: 6.6
D1: Duloxetine 60 mg/d Baseline HAM-D-17: Dizziness:
D2: Placebo D1: 21.42 (4.11) D1: 20.3
D2: 21.14 (3.72) D2: 8.2
Baseline 100mm VAS (overall pain): Insomnia:
D1: 29.02 (25.10) D1: 15.4
D2: 28.16 (23.21) D2: 5.7
Baseline HAM-A: Nausea:
NR D1: 46.3
D2: 9.0
Sexual dysfunction:
NR but 2.4% of DUL-treated patients dropped out due to abnormal ejaculation
Somnolence:
D1: 21.1
D2: 4.9
Author: Research objective: Inclusion criteria: Mean age (yrs): Pain outcomes: Cardiovascular adverse events (new hypertension): Overall attrition rate:
Detke et al., 2002To evaluate efficacy of DUL compared to placebo for treatment of emotional and painful physical symptoms of MDD
  • Adults 18 or older
  • MDD according to DSM-IV
  • Minimum HAM-D-17 score of 15
  • CGI-S of 4 or more
D1: 41Mean reduction in VAS for overall pain was ~10 mm for DUL compared to ~6 mm for placebo at endpoint (change score estimated from figure; P = 0.037) D1: 0.836.3%
Country and setting: Duration of study: Note: Painful symptoms not required for inclusion D2: 41 D2: 0 ITT Analysis
United States, multicenter (21 psychiatric clinical sites)9 wks Exclusion criteria: Sex (% female): Constipation: Yes
Funding: Study design:
  • Additional mental illness or organic mental disorder
  • Psychotherapy within 6 wks
  • Substance abuse or dependence (within 1 yr)
  • Clinically sig medical disease
  • Treatment resistant depression or lack of response of current MDD episode to 2 prior courses of therapy
D1: 66 D1: 14.1 Quality rating:
Not reported but authors worked for Eli Lilly and CompanyRCT D2: 71 D2: 5.0Fair
Overall study N: Race (% white): Diarrhea:
267 D1: 78.1 D1: 10.2
Intervention: D2: 78.4 D2: 7.9
D1: Duloxetine 60 mg/d Baseline HAM-D: Dizziness:
D2: Placebo D1: 20.33 (3.39) D1: 14.8
D2: 20.46 (3.39) D2: 2.9
Baseline 100mm VAS (overall pain): Headache:
D1: 25.40 (23.98) D1: 25.8
D2: 26.20 (23.10) D2: 22.3
Baseline HAM-A: Insomnia:
NR D1: 16.4
D2: 13.7
Nausea:
D1: 29.7
D2: 11.5
Author: Research objective: Inclusion criteria: Mean age (yrs) in sleep disturbance subgroup: Depression outcomes in patients with sleep disturbance: Changes in weight (increase 7%): Overall attrition rate:
Fava et al., 2002To compare efficacy and tolerability of FLUO vs. PAR and SER for treatment of depression associated with sleep disturbance
  • Adults 18 or older
  • Outpatients
  • MDD according to DSM-IV
  • Minimum HAM-D-17 score of 16
D1: 42.2No statistically sig diffs between FLUO, PAR and SER in HAM-D-17 total score improvement (overall P = 0.853) D1: 1.649%
Country and setting: Duration of study: Note: Sleep disturbance defined as HAM-D Sleep Disturbance Factor score of at least 4 D2: 41.9 Sleep outcomes: D2: 9.0 ITT Analysis:
United States, multicenter (15 sites)10 to 16 wks (depending on response to initial dose; all received 6 wks of therapy at effective dose) Exclusion criteria: D3: 43.0Improvement in HAM-D Sleep Disturbance factor was similar for all 3 groups: FLUO (-3.1), PAR (-2.9), SER (-3.1) (overall P = 0.852) D3: 2.9Yes
Funding: Study design:
  • Additional mental illness or organic mental disorder
  • Concomitant psychotropic medications
  • Substance use or dependence (within 6 mos)
  • Pregnant, lactating, or child-bearing potential without contraception
  • Clinically sig medical disease
  • Suicide risk (serious)
  • Seizure within 1 yr
  • Response to placebo in lead-in phase
Sex (% female) in sleep disturbance subgroup: Diarrhea: Quality rating:
Eli Lilly and CompanyRCT D1: 60.5 D3: 26.0Fair
Overall study N: D2: 65.2 Headache:
284 overall; 125 in sleep disturbance subgroup D3: 63.4 D1: 25.0
Intervention: Race (% white): D2: 21.9
D1: Fluoxetine: 20–60 mg/dNR D3: 28.1
D2: Paroxetine: 20–60 mg/d Baseline HAM-D-17 in sleep disturbance subgroup: Insomnia:
D3: Sertraline: 50–200 mg/d D1: 23.4 (3.9) D2: 20.8
D2: 22.6 (4.2) D3: 26.0
D3: 23.5 (3.9) Nausea:
Baseline HAM-D Sleep Disturbance factor in sleep disturbance subgroup: D2: 25.0
D1: 5.1 (0.9) D3: 20.8
D2: 4.8 (0.8) Sexual dysfunction (abnormal ejaculation):
D3: 5.1 (0.8) D2: 20.0 (of males)
Baseline HAM-A:
NR
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in patients with anxiety: Diarrhea: Overall attrition rate:
Fava et al., 2000To compare efficacy and tolerability of FLUO vs. PAR and SER for treatment of anxious depression
  • Adults 18 or older
  • Outpatients
  • MDD according to DSM-IV
  • Minimum HAM-D-17 score of 16
D1: 40.3No statistically sig diffs between FLUO, SER and PAR in improvement on HAM-D-17 total scores (overall P = 0.323) D2: 20.0NR
Country and setting: Duration of study: Note: High anxiety defined as HAM-D Anxiety/Somatization Factor score of at least 7 D2: 41.4Response rates were similar for FLUO, PAR, and SER (73%, 77%, and 86%, overall P = 0.405). Remission rates were also similar (53%, 50%, and 62%, overall P = 0.588) D3: 25.6 ITT Analysis
United States, multicenter (15 sites)10 to 16 wks (depending on response to initial dose; all received 6 wks of therapy at effective dose) Exclusion criteria: D3: 44..1 Anxiety outcomes: Headache: Yes
Funding: Study design:
  • Additional mental illness or organic mental disorder
  • Concomitant psychotropic medications
  • Substance use or dependence (within 6 mos)
  • Pregnant, lactating, or child-bearing potential without contraception
  • Clinically sig medical disease
  • Suicide risk
  • Seizure within 1 yr
  • Response to placebo in lead-in phase
Sex (% female): No statistically sig diffs between FLUO, SER and PAR in improvement on HAM-D Anxiety/Somatization Factor scores (overall P = 0.199) D1: 22.9 Quality rating:
Eli Lilly and CompanyRCT D1: 65.7 D2: 23.3Fair
Overall study N: D2: 66.7 D3: 25.6
108 (subset of patients with high anxiety from larger trial involving 284 patients with MDD) D3: 62.8 Insomnia:
Intervention: Race (% white): D1: 17.1
D1: Fluoxetine: 20–60 mg/d (mean 44)NR D2: 23.3
D2: Paroxetine: 20–60 mg/d (mean 36) Baseline HAM-D-17: D3: 23.3
D3: Sertraline: 50–200 mg/d (mean 104) D1: 23.6 (3.9) Nausea:
D2: 25.0 (3.8) D2: 26.7
D3: 23.9 (3.4) Somnolence:
Baseline HAM-D Anxiety/Somatization factor: D1: 11.4
D1: 7.8 (0.9) D2: 10.0
D2: 8.2 (1.3) D3: 16.3
D3: 8.1 (1.3)
Baseline HAM-A:
NR
Author: Research objective: Inclusion criteria: Mean age (yrs): Anxiety outcomes: Cardiovascular adverse events: Overall attrition rate:
Fava et al., 1998To evaluate efficacy of FLUO vs. PAR vs. placebo for treatment of depression
  • Outpatients
  • Minimum HAM-D-17 score of 18
  • Raskin Depression score of 8 or more
  • Raskin score higher than Covi Anxiety Scale score
Overall: 41.3Improvement in Covi Anxiety was similar for FLUO (1.2), PAR (1.2) and placebo (1.1; P = NR) D1: 1128%
Country and setting: Duration of study: Exclusion criteria: Sex (% female): D2: 5 ITT Analysis:
United States, multicenter (5 sites)12 wks
  • Additional mental illnesses or organic mental disorder
  • Concomitant psychotherapeutic medications
  • Alcohol or drug abuse (within 6 mos)
  • ECT within 3 mos
  • Investigational drug within 1 mo
  • Suicidal (high risk)
  • Clinically sig medical disease
  • Pregnant, lactating, or child-bearing potential without contraception
  • Placebo response during washout (25% improvement on HAM-D)
Overall: 50 D3: 11Yes
Funding: Study design: Race (% white): Insomnia: Quality rating:
SmithKline BeechamPooled analysis of data from 5 sites of 2 multicenter trialsNR D1: 20Fair
Overall study N: Baseline HAM-D-17: D2: 29
128 D1: 23.9 (3.8) D3: 11
Intervention: D2: 23.1 (3.4) Sexual dysfunction:
D1: Fluoxetine 20–80 mg/d D3: 23.7 (2.7) D1: 7
D2: Paroxetine 20–50 mg/d Baseline Covi Anxiety score: D2: 25
D3: Placebo D1: 6.3 (1.7) D3: 0
D2: 6.2 (1.7) Somnolence:
D3: 5.8 (1.2) D1: 26
Baseline HAM-A: D2: 35
NR D3: 11
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression results in patients with melancholia: Overall adverse events: Overall attrition rate:
Flament et al., 1999To compare response rates of FLUO vs. SER for treatment of depression in subgroups of patients with depression
  • Adults 18 or older
  • Outpatients
  • MDD or bipolar, depressed by DSM-III-R criteria
  • Minimum HAM-D-17 score of 18
  • Raskin Depression score higher than Covi Anxiety score
D1: 49.9Mean HAM-D change did not differ between groups (-9.8 FLUO vs. -11.0 SER). Response rates were higher for SER (59%) vs. FLUO (44%) (P < 0.05) D1: 6013.3%
Country and setting: Duration of study: Exclusion criteria: D2: 49.9 Depression results in anxiety: D2: 57 ITT Analysis:
UK, multicenter (20 psychiatric clinics)6 wks
  • Additional mental illnesses or organic mental disorder
  • Concomitant psychotherapeutic drugs
  • Concomitant ECT or psychotherapy
  • Substance use or dependence (within 6 mos)
  • Pregnant, lactating, or child-bearing potential without contraception
  • Clinically sig medical disease
  • Suicide risk
  • Placebo response during washout
  • Previous use of study drugs
Sex (% female): FLUO and SER groups had similar HAM-D mean change (-10.6 vs. -9.7) and response rates (48% vs. 47%; P = NR)Yes
Funding: Study design: D1: 65 Depression results in psychomotor change: Quality rating:
Not reported, but 2nd author employed by Pfizer IncRCT D2: 57In retardation, HAM-D change and response were similar (Change/response: -10.7/46% for FLUO vs. -9.1/48% for SER; P = NR). In agitation, HAM-D improvement was 8.7 for FLUO vs. 12.4 for SER (P = 0.02); response rate was 39% for FLUO vs. 62% for SER (P = 0.04)Fair
Overall study N: Race (% white):
286 randomized; 248 included in analysis; 174 in melancholia subgroup (defined by DSM-III-R criteria); 131 in anxiety subgroup (7 or more on Covi Anxiety Scale); 47 in psychomotor retardation group (HAM-D item 8 ≥2 and item 9 ≤ 1); 78 in psychomotor agitation subgroup (HAM-D item 8 ≤ 1 and item 9 ≥2)NR
Intervention: Baseline HAM-D-17:
D1: Fluoxetine 20–40 mg/d (mean 25) D1: 23.4
D2: Sertraline 50–100 mg/d (mean 62.5) D2: 23.2
Baseline HAM-A:
NR
Author: Research objective: Inclusion criteria: Mean age (yrs): Anxiety outcomes: Diarrhea: Overall attrition rate:
Gagiano, 1993To evaluate efficacy of FLUO and PAR in patients with MDD
  • Adults 18 to 65
  • Outpatients
  • MDD according to DSM-III-R
  • Minimum HAM-D-21 score of 18
D1: 39.6Improvement in HAM-A scores was similar for FLUO and PAR groups (P = NR) D1: 1321%
Country and setting: Duration of study: Exclusion criteria: D2: 37.8 D2: 13 ITT Analysis:
South Africa6 wks
  • Additional mental illness or organic mental disorder
  • Recent psychotherapeutic medications
  • ECT within 3 mos
  • Alcohol or drug abuse
  • Pregnant or lactating
  • Clinically sig medical disease
  • Suicidal (severe risk)
Sex (% female): Headache: Yes
University hospital Study design: D1: 80 D1: 47 Quality rating:
Funding: RCT D2: 80 D2: 53Fair
NR Overall study N: Race (% white): Insomnia:
90NR D1: 20
Intervention: Baseline HAM-D-21: D2: 11
D1: Fluoxetine 20–60 mg/d D1: 24.5 (5.0) Nausea:
D2: Paroxetine 20–40 mg/d D2: 25.0 (4.7) D1: 33
Baseline HAM-A: D2: 36
D1: 22.6 (5.1)
D2: 23.4 (5.5)
Author: Research objective: Inclusion criteria: Mean age (yrs): Pain outcomes: Constipation: Overall attrition rate:
Goldstein et al., 2004To evaluate DUL vs. PAR and placebo for treatment of emotional and painful physical symptoms in patients with MDD
  • Adults 18 or older
  • MDD according to DSM-IV
  • Minimum HAM-D-17 score of 15
  • CGI-S of 4 or more
D1: 41Median change in VAS overall pain was 0 for placebo, -4 mm for DUL 40 mg (P vs. placebo = 0.172), -7.5 mm for DUL 80 mg (P vs. placebo = 0.005), and -3 for placebo (P vs. placebo = 0.088) D1: 8.141%
Country and setting: Duration of study: Note: Painful symptoms not required for inclusion D2: 41 D2: 8.8 ITT Analysis:
United States, multicenter (19 psychiatric research centers)8 wks Exclusion criteria: D3: 40 D3: 13.8Yes
Funding: Study design:
  • Additional mental illnesses or organic mental disorder (except anxiety disorders)
  • Substance abuse or dependence (within 1 yr)
  • Positive urine drug screen
  • Lack of response of current MDD episode to 2 prior courses of therapy
D4: 40 D4: 3.4 Quality rating:
Eli Lilly and CompanyRCT Sex (% female): Dizziness: Poor: High overall attrition
Overall study N: D1: 56 D1: 4.7
353 D2: 62 D2: 16.5
Intervention: D3: 64 D3: 10.3
D1: Duloxetine 40 mg/d D4: 64 D4: 5.6
D2: Duloxetine 80 mg/d Race (% white): Insomnia:
D3: Paroxetine 20 mg/d D1: 84 D1: 17.4
D4: Placebo D2: 85 D2: 19.8
D3: 74 D3: 8.0
D4: 83 D4: 5.6
Baseline HAM-D-17: Nausea:
D1: 18.74 (5.97) D1: 22.1
D2: 17.86 (4.66) D2: 25.3
D3: 17.83 (5.19) D3: 16.1
D4: 17.20 (5.08) D4: 2.2
Baseline HAM-A: Somnolence:
D1: 15.24 (5.87) D1: 17.4
D2: 14.70 (4.83) D2: 11.0
D3: 14.70 (6.00) D3: 8.0
D4: 14.47 (5.3) D4: 2.2
Median baseline 100mm VAS (overall pain): Sweating (increase):
D1: 17.5 D1: 9.3
D2: 18.0 D2: 12.1
D3: 15.0 D3: 6.9
D4: 15.0 D4: 0.0
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in patients with anxiety: NR Overall attrition rate:
Joliat et al., 2004To assess efficacy of FLUO 20 mg daily vs. FLUO 90 mg wkly vs. placebo in continuation treatment of depression in patients with MDD and associated anxiety who initially responded to therapy
  • Adults 18 to 65 (Study 1) and 18 to 80 (Study 2)
  • Outpatients
  • MDD according to DSM-III-R or IV
  • Minimum HAM-D-17 score of 16 for Study 1 and 18 for Study 2. Study 2 also required CGI-S score of 4 or more
  • Duration of 1 mo or more
D1: 40.6Relapse rates for patients with anxiety were 28.5% in FLUO wkly group, 27.8% in FLUO daily group, and 53.3% in placebo-treated group (P = NR)NR
Pooled data from
1.

Reimherr et al., 1998

2.

Schmidt et al., 2000

Duration of study: Note: High anxiety defined as score of 7 or more on HAM-D Anxiety-Somatization subscale D2: 40.8 Anxiety outcomes: ITT Analysis
Country and setting: 25 wks Exclusion criteria: D3: 41.5HAM-D Anxiety-Somatization scores increased (worsened) 1.92 and 1.93 in FLUO daily and wkly groups, respectively, and 3.12 points in placebo group (P = NR)Yes
United States, multicenter Study design:
  • Additional mental illness or organic mental disorder
  • Substance abuse (within 1 yr)
  • Pregnant or lactating
  • Unstable medical conditions
  • Lack of response of current episode to FLUO or to 2 prior courses of therapy
Sex (% female): Quality rating:
Funding: Pooled analysis of data from 2 RCTs D1: 72.1Fair
Eli Lilly and Company Overall study N: D2: 70.1
374 with anxiety (data for 425 patients without anxiety not considered for KQ 3) D3: 76.2
Intervention: Race (% white):
D1: Fluoxetine 20 mg/d D1: 84.3
D2: Fluoxetine 90 mg/wk D2: 91.8
D3: Placebo D3: 86.7
Baseline HAM-D:
D1: 3.79(2.56)
D2: 4.17(2.77)
D3: 3.45(2.34)
Baseline HAM-A:
NR
Author: Research objective: Inclusion criteria: Mean age (yrs): Anxiety outcomes in patients with anxiety: Dropouts due to dizziness: Overall attrition rate:
Khan et al., 1998To evaluate efficacy of 3 different doses of VEN vs. placebo for treatment of MDD or MDD with associated anxiety
  • Adults 18 or older
  • Outpatients
  • MDD according to DSM-III -R
  • Minimum HAM-D-21 score of 20
  • Depression symptoms for at least 1 mo
D1: 43.3All 3 VEN-treated groups had statistically sig improvement in HAM-D Anxiety-Psychic Item and Anxiety-Somatization Factor scores compared to placebo group (P < 0.05) D1: 5NR
Country and setting: Duration of study: Note: Anxiety defined as score of 2 or more on HAM-D Anxiety-Psychic Item D2: 40.0 D2: 2 ITT Analysis
United States, multicenter (12 sites)12 wks Exclusion criteria: D3: 43.6 D3: 6Yes
Funding: Study design:
  • Additional mental illnesses or organic mental disorder
  • Concomitant or recent psychotherapeutic drugs or ECT
  • Drug or alcohol dependence (within 2 yrs)
  • Suicidal
  • Women with child-bearing potential
  • Clinically sig medical disease
  • Decrease of >20% in HAM-D during palcebo washout
D4: 40.2 D4: 1 Quality rating:
Not reported but 3 authors employed by Wyeth-AyerstRCT Sex (% female): Dropouts due to insomnia: Fair
Overall study N: D1: 68 D1: 5
403 randomized; 353 in modified ITT analysis; 346 with associated anxiety D2: 64 D2: 3
Intervention: D3: 60 D3: 5
D1: Venlafaxine 75 mg/d D4: 61 D4: 0
D2: Venlafaxine 150 mg/d Race (% white): Dropouts due to nausea:
D3: Venlafaxine 200 mg/dNR D1: 8
D4: Placebo Baseline HAM-D: D2: 7
D1: 24.3 D3: 17
D2: 24.5 D4: 1
D3: 24.8 Dropouts due to somnolence:
D4: 25.1 D1: 7
Baseline HAM-A: D2: 4
NR D3: 4
D4: 0
Author: Research objective: Inclusion criteria: Mean age (yrs): Somatization severity outcomes: Dropouts due to changes in weight (increase): Overall attrition rate:
Kroenke et al., 2001To compare effectiveness of PAR, FLUO and SER for treatment of depression in primary care
  • Adults 18 or older
  • Depressive disorder diagnosed by primary care physician
  • Access to telephone at home
D1: 47.1Scores on Patient Health Questionnaire Somatization Severity scale (possible range 0–28) improved similarly in all 3 treatment groups. Scores decreased 3.1, 3.2, and 4.1 points for FLUO, PAR, and SER-treated groups (nonsig diff; P value NR) D1: 024.3%
Country and setting: Duration of study: Exclusion criteria: D2: 47.2 D2: 1 ITT Analysis
United States, multicenter (37 primary care clinics)9 mos
  • Concomitant psychotherapeutic medications (SSRI within 2 mos or current non-SSRI antidepressant)
  • Suicidal tendencies (active)
  • Bipolar disorder, severe cognitive impairment, terminal illness
  • Active cocaine or opiate abuse
  • Pregnant, lactating or pregnancy planned within 9 mos
  • Unable to read, write, or speak English
D3: 44.1 D3: 1Yes
Funding: Study design: Sex (% female): Dropouts due to gastrointestinal symptoms: Quality rating:
Eli Lilly and CompanyRCT D1: 86 D1: 4Fair
Overall study N: D2: 76 D2: 8
601 randomized; 546 included in analysis D3: 75 D3: 4
Intervention: Race (% white): Dropouts due to headache:
D1: Fluoxetine: 20 mg/d (mean 23.4) D1: 88 D1: 2
D2: Paroxetine: 20 mg/d (mean 23.5) D2: 85 D2: 3
D3: Sertraline: 50 mg/d (mean 72.8) D3: 79 D3: 1
Baseline HAM-D: Dropouts due to sexual dysfunction:
NR D1: 1
Baseline HAM-A: D2: 2
NR D3: 0
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in patients with sleep problems Insomnia: Overall attrition rate:
Lader et al., 2005To evaluate effect of ESC vs. CIT and placebo on sleep in patients with depression
  • Adults 18 to 65 (Study 1, 3), 18 to 80 (Study 2)
  • Outpatients
  • MDD according to DSM-IV
  • Minimum MADRS score of 22
D1: 42Mean improvement in MADRS total score was 16.47 points for ESC group (P < 0.05 vs. CIT; P < 0.05 vs. placebo) compared to 14.02 for CIT (P vs. placebo not sig) and 12.2 for placebo D1: 8.616.7%
Pooled data from
1.

Burke et al., 2002

2.

Rapaportet al., 2004

3.

Lepola et al., 2003

Duration of study: Note: Sleep problems defined as MADRS item 4 score of 4 or more (possible range 0–6) D2: 41 Sleep outcomes: D2: 9.2 ITT Analysis
Country and setting: 8 wks Exclusion criteria: D3: 42Mean improvement in MADRS item 4 was 1.65 points for ESC (P < 0.01 vs. CIT; P < 0.01 vs. placebo), 1.31 for CIT (P vs. placebo not sig), and 1.26 for placebo. Rate of improvement (end MADRS sleep score of 0 or 1) was 43.6% for ESC vs. 28.4% for CIT and 24.4% for placebo (P < 0.001) D3: 3.9Yes
United States and Europe Study design:
  • Concomitant psychotherapeutic medications
  • Full criteria not reported
Sex (% female): Somnolence: Quality rating:
Funding: Pooled analysis of 3 RCTs D1: 61 D1: 4.7Fair
H. Lundbeck A/S, Forest Laboratories Overall study N: D2: 67 D2: 6.9
1321 included in analysis; 638 with sleep problems D3: 64 D3: 2.2
Intervention: Race (% white):
D1: Citalopram: 20–40 mg/d (mean 28.9)NR
D2: Escitalopram: 10–20 mg/d (mean 13.3) Baseline HAM-D:
D3: PlaceboNR
Baseline MADRS:
D1: 28.9 (4.6)
D2: 28.7 (4.5)
D3: 29.0 (4.6)
Baseline HAM-A:
NR
Author: Research objective: Inclusion criteria: Mean age (yrs): Anxiety outcomes: Overall adverse events: Overall attrition rate:
Leinonen et al., 1999To evaluate efficacy of MIR vs. CIT for treatment of major depression
  • Adults 18 to 65
  • Outpatient and inpatient
  • MDD according to DSM-IV
  • Minimum MADRS score of 22
  • Duration of current depression episode less than 12 mos
D1: 41.1Mean reduction in HAM-A scores was similar (approximately -13 points) in both treatment groups (change estimated from figure; P = 0.75) D1: 70.719.1%
Country and setting: Duration of study: Exclusion criteria: D2: 42.1 D2: 66.4 ITT Analysis
European, multicenter (21 psychiatric sites)8 wks
  • Additional mental illnesses or organic mental disorder
  • Concomitant or recent psychotherapeutic medications
  • ECT within 3 mos
  • Substance abuse (within 12 mos)
  • Pregnant or lactating
  • Clinically sig medical disease
  • Suicidal (high risk)
  • Lack of response of current MDD episode to 2 prior courses of therapy
  • Placebo response during washout (25% improvement on MADRS)
Sex (% female): Changes in weight (increase): Yes
Funding: Study design: D1: 57.1 D1: 4.5 Quality rating:
OrganonRCT D2: 66.9 D2: 15.3Fair
Overall study N: Race (% white): Diarrhea:
270 randomized; 269 included in analysisNR D1: 6.0
Intervention: Baseline HAM-D: D2: 2.9
D1: Citalopram 20–60mg/d (mean 36.6)NR Dizziness:
D2: Mirtazapine 15–60mg/d (mean 35.9) Baseline MADRS: D1: 4.5
D1: 29.1 (4.5) D2: 8.8
D2: 29.6 (4.9) Headache:
Baseline HAM-A: D1: 14.3
D1: 20.9 (6.1) D2: 9.5
D2: 21.1 (6.2) Nausea:
D1: 20.2
D2: 10.2
Somnolence:
D1: 6
D2: 8
Fatigue:
D1: 13.5
D2: 12.4
Sweating (increase):
D1: 15.0
D2: 2.2
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in patients with melancholia: NR Overall attrition rate:
Mallinckrodt et al., 2005To compare efficacy of DUL for treatment of depression in patients with melancholia to those without melancholia
  • Adults 18 or older
  • MDD according to DSM-IV
  • Minimum HAM-D-17 score of 15
  • CGI-S score of 4 or more
All melancholic: 42.1Mean reduction in HAM-D-17 score was 8.97 for DUL-treated group and 6.57 for those receiving placebo (P < 0.001)NR
Country and setting: Duration of study: Note: Melancholic features defined by DSM-IV criteria Sex (% female): ITT Analysis
United States, multicenter9 wks Exclusion criteria: All melancholic: 69.5Yes
Funding: Study design:
  • Additional mental illness or organic mental disorder
  • Concomitant psychotherapeutic or chronic prescription analgesic drugs
  • Substance abuse or dependence (within one yr); positive urine drug screen
  • Clinically sig medical disease
  • Suicidal (serious risk)
  • Lack of response of current MDD episode to 2 prior courses of therapy
Race (% white): Quality rating:
Eli Lilly and CompanyPooled analysis of 8 RCTs (all RCTs included in DUL's New Drug Application to FDA)NRFair
Overall study N: Baseline HAM-D:
1572 with melancholiaAll melancholic: 22.3 (3.9)
Intervention: Baseline HAM-A:
D1: Duloxetine 40–120 mgNR
D2: Placebo
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in patients with insomnia: Constipation: Overall attrition rate (%):
Rush et al., 1998To evaluate effects of FLUO vs. NEF on sleep in patients with depression and insomnia
  • Adults 19 to 55
  • Outpatients
  • MDD according to DSM-III-R
  • Minimum HAM-D-17 score of 18
  • One of following sleep problems was required: difficulty falling asleep, waking up during night, or inability to fall asleep again after getting up
D1: 37Mean improvement in HAM-D-17 was 12.2 for FLUO-treated group and 11.4 for NEF-treated group (95% CI for diff: -1.7, 2.8) D1: 1117%
Country and setting: Duration of study: Exclusion criteria: D2: 36Response rates were similar for FLUO (45%) and NEF (47%; P = NR) D2: 17 ITT Analysis
United States, multicenter (10 sites)8 wks
  • Additional mental illness or organic mental disorder
  • Substance use disorder (within 1 yr)
  • Clinically sig medical disease
  • Pregnant, lactating, or child-bearing potential without contraception
  • Shift-workers; sleep/wake disorder on polysomnograph
Sex (% female): Sleep outcomes: Diarrhea: Yes
Funding: Study design: D1: 70Mean improvement in HAM-D Sleep Disturbance Factor was 1.6 points for FLUO-treated group and 2.3 for NEF-treated group (P < 0.05) D1: 26 Quality rating:
Bristol-Myers SquibbPooled analysis of 3 RCTs D2: 59Improvement in IDS-SR Sleep Factor was 1.7 points for FLUO-treated group and 2.4 for NEF-treated group (P < 0.01) D2: 16Fair
Overall study N: Race (% white): Dizziness:
125 randomized; 122 included in analysis D1: 85 D1: 8
Intervention: D2: 78 D2: 22
D1: Fluoxetine 20–40 mg/d (mean 32) Baseline HAM-D: Headache:
D2: Nefazodone 200–500 mg/d (mean 424) D1: 23.3 (2.7) D1: 48
D2: 22.9 (2.9) D2: 56
Baseline HAM-D Sleep Disturbance Factor: Insomnia:
D1: 4.2 (1.3) D1: 11
D2: 4.2 (1.3) D2: 6
Baseline Depression Symptomatology-Self Report (IDS-SR) Sleep Factor: Nausea:
D1: 5.8 (2.1) D1: 25
D2: 5.3 (2.2) D2: 36
Baseline HAM-A: Sexual dysfunction:
NR D1: 11 of males
D2: 0 of males
Somnolence:
D1: 21
D2: 22
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in patients with high anxiety: Diarrhea: Overall attrition rate (%):
Rush et al., 2001 (original report: Kavoussi, 1997)To determine whether baseline anxiety levels are associated with response to BUP SR and SER
  • Adults 18 or older
  • MDD according to DSM-IV
  • Minimum HAM-D-21 score of 18
  • Depression duration 1 to 24 mos
D1: 39In patients with high anxiety (top quartile of HAM-A scores), response and remission rates were similar for BUP SR and SER (estimated from figure: approximately 60% remission and 70% response in both groups, P = NR) D1: 331%
Country and setting: Duration of study: Exclusion criteria: D2: 40 Anxiety outcomes in all patients: D2: 22 ITT Analysis
United States, multicenter16 wks
  • Concomitant or recent psychotherapeutic drugs
  • Suicidal (active)
  • Pregnant or lactating
  • History of eating disorder or predisposition to seizures
  • Previous treatment with BUP or SER
Sex (% female): Mean reduction in HAM-A was 9.7 for BUP-treated group and 10.0 for SER treated group (P = NR) Dizziness: Yes
Funding: Study design: D1: 48 D1: 8 Quality rating:
Glaxo-WellcomeRCT D2: 48 D2: 5Fair
Overall study N: Race (% white): Headache:
248 D1: 93 D1: 34
Intervention: D2: 94 D2: 32
D1: Bupropion SR 100–300 mg/d Baseline HAM-D: Insomnia:
D2: Sertraline 50–200 mg/d D1: 24.8 (4.6) D1: 18
D2: 24.8 (4.6) D2: 19
Baseline HAM-A: Nausea:
D1: 16.6 (5.2) D1: 10
D2: 16.6 (5.4) D2: 30
Sexual dysfunction (orgasm in men):
D1: 10
D2: 61
Sexual dysfunction (orgasm in women):
D1: 7
D2: 41
Somnolence:
D1: 2
D2: 13
Sweating (increase):
D1: 2
D2: 10
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in anxiety subgroup: Dizziness: Overall attrition rate (%):
Sir et al., 2005To evaluate diffs in efficacy between SER and VEN XR on measures of QOL, depression, anxiety and pain in patients with major depression
  • Adults 18 or older
  • Outpatients
  • MDD according to DSM-IV
  • Minimum HAM-D-17 score of 18
D1: 37.3Mean reduction in HAM-D was 17.3 for SER and 14.8 for VEN XR (P = 0.70) D1: 32.923%
Country and setting: Duration of study: Note: Anxious depression subgroup defined by HAM-D Anxiety-Somatization score of 7 or more D2: 36.8Response rates SER 79.6% VEN 68.9% (P = 0.26) D2: 26.2 ITT Analysis:
Australia and Turkey (13 sites)8 wks Exclusion criteria: Sex (% female): Remission rates were SER 63.0% VEN 54.1 (P = 0.44) Headache: Quality rating:
Funding: Study design:
  • Additional mental illnesses or organic mental disorder
  • Substance abuse or dependence (within 6 mos)
  • Pregnant or child-bearing potential without contraception
  • Lack of response of current MDD episode to 2 prior courses of therapy
  • History of nonresponse to SER or VEN
D1: 72.2 Anxiety outcomes: D1: 44.3Fair
Pfizer, IncRCT D2: 66.7In overall study population, mean reduction in HAM-A was similar for treatment groups: 14.1 for SER vs. 12.9 for VEN XR (P = 0.32) D2: 32.1
Overall study N: Race (% white): In high-anxiety subgroup, response on HAM-D Anxiety-Somatization subscale was similar for treatment arms: 83.3% for SER, 70.5% for VEN (P = 0.12) Insomnia:
163 overall; 120 in anxiety subgroup D1: 96.2 D1: 35.4
Intervention: D2: 100 D2: 27.4
D1: Sertraline 50–150 mg/d Baseline HAM-D: Nausea:
D2: Venlafaxine XR 75–225 mg/d D1: 23.4 (4.4) D1: 51.9
D2: 23.5 (4.4) D2: 47.6
Baseline HAM-A: Somnolence:
NR D1: 21.5
D2: 26.2
Sweating (increase):
D1: 31.6
D2: 21.4
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in patients with anxiety: Dizziness: Overall attrition rate:
Trivedi et al., 2001 and Rush et al., 2001To compare effects of bupropion SR and SER on anxiety in patients with MDD
  • Adults 18 or older
  • MDD according to DSM-IV
  • Recurrent major depression episode of 2 to 24 mo duration
  • Minimum HAM-D-21 score of 18
D1: 37Response rates were similar for BUP SR, SER, and placebo (approximately 70%, 64% and 58%; rates estimated from figure; P = NR). Remission rates were also similar for all 3 treatment groups (P = NR) D1: 728%
Country and setting: Duration of study: Note: Anxiety subgroup defined as top quartile on HAM-A (score > 24) D2: 37 Anxiety outcomes in all patients: D2: 8 ITT Analysis
United States, multicenter8 wks Exclusion criteria: D3: 38Mean reduction in HAM-A was similar for BUP SR and SER-treated groups (9.9 and 9.4 points) and slightly less for those receiving placebo (8.4 points). No statistically sig diff between active drug groups (P > 0.41). Diff between active drug and placebo was statistically sig for BUP group (P = 0.04) but not for SER (P = NR) D3: 5Yes
Funding: Study design:
  • Additional mental illness or organic mental disorder (except GAD)
  • Concomitant psychotherapeutic medications (within one wk)
  • Substance abuse or dependence (within one yr)
  • Pregnant or lactating
  • Prior treatment with BUP or SER
Sex (% female): Insomnia: Quality rating:
Glaxo Wellcome IncAnalysis of pooled data from 2 RCTs D1: 53 D1: 16Fair
Overall study N: D2: 51 D2: 18
724 randomized; 692 included in analysis D3: 55 D3: 5
Intervention: Race (% white): Somnolence:
D1: Bupropion SR 150–400 mg/d D1: 87 D1: 3
D2: Sertraline 50–200 mg/d D2: 91 D2: 13
D3: Placebo D3: 88 D3: 5
Baseline HAM-D:
D1: 25.2 (5.2)
D2: 25.2 (5.2)
D3: 24.9 (5.2)
Baseline HAM-A:
D1: 18.8 (7.3)
D2: 18.6 (7.4)
D3: 18.6 (7.1)
Author: Research objective: Inclusion criteria: Mean age (yrs): Depression outcomes in melancholia: Overall adverse events: Overall attrition rate:
Tzanakaki et al., 2000To evaluate efficacy of FLUO vs. VEN in patients with major depression and melancholia
  • Adults 18 to 64
  • Outpatient or hospitalized
  • MDD with melancholia according to DSM-IV
  • MADRS of 25 or more
  • Depression symptoms for one mo or more
D1: 49Response rates were similar for FLUO-treated group (58%) and VEN group (65%; P = NR). Remission rates were similar for FLUO (36%) and VEN (41%; P = NR) D1: 46.322%
Country and setting: Duration of study: Exclusion criteria: D2: 47 D2: 49.1 ITT Analysis
Greece and Italy, multicenter6 wks
  • Additional mental illnesses or organic mental disorder
  • Concomitant or recent psychotherapeutic drugs
  • ECT within 30 days
  • Drug or alcohol dependence (within 2 yrs)
  • Pregnant or without contraception
  • Clinically sig medical disease
  • Investigational drug use within 30 days
  • Suicidal (acute)
Sex (% female): Constipation: Yes
Funding: Study design: D1: 83 D1: 1.9 Quality rating:
Wyeth-Ayerst InternationalRCT D2: 75 D2: 7.3Fair
Overall study N: Race (% white): Dizziness:
109NR D1: 0
Intervention: Baseline HAM-D: D2: 5.5
D1: Fluoxetine 60 mg/d D1: 27.1 (5.6) Headache:
D2: Venlafaxine 225 mg/d D2: 27.8 (5.6) D1: 1.9
Baseline HAM-A: D2: 5.5
NR Insomnia:
D1: 1.9
D2: 12.7
Nausea:
D1: 14.8
D2: 5.5
Sweating (increase):
D1: 3.7
D2: 5.5
Author: Research objective: Inclusion criteria: Mean age (yrs): Sleep outcomes: Overall adverse events: Overall attrition rate:
Versiani, 2005To compare efficacy and tolerability of MIR and FLUO in severe MDD
  • Adults 18 to 65
  • MDD according to DSM-IV
  • Minimum HAM-D-17 score of 25
D1: 47Scores on Leeds Sleep Evaluation Questionnaire improved similarly for both groups D1: 4514%
Country and setting: Duration of study: Exclusion criteria: D2: 43 D2: 50 ITT Analysis
Europe and South America, multicenter (30 sites)8 wks
  • Current depression episode duration >12 mos
  • Additional mental illnesses or organic mental disorder
  • Concomitant or recent psychotherapeutic drugs
  • Investigational drug use within 30 days
  • ECT within 3 mos
  • Alcohol or substance abuse (within 6 mos)
  • Pregnant or lactating
  • Clinically sig medical disease
  • Suicidal risk
  • Response during placebo washout (25% improvement in HAM-D-17)
Sex (% female): Changes in weight (increase): Yes
Funding: Study design: D1: 69 D1: 1.3 Quality rating:
OrganonRCT D2: 74 D2: 6.9Fair
Overall study N: Race (% white): Dizziness:
299 randomized; 292 included in analysisNR D1: 12.8
Intervention: Baseline HAM-D: D2: 9
D1: Fluoxetine 20–40 mg/d D1: 28 (3) Headache:
D2: Mirtazapine 30–60 mg/d D2: 29 (3) D1: 18.8
Baseline HAM-A: D2: 19.3
NR Insomnia:
D1: 8.7
D2: 4.8
Nausea:
D1: 24.1
D2: 15.9
Somnolence:
D1: 9.4
D2: 13.8

From: Appendix D, Evidence Tables

Cover of Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression
Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression [Internet].
Comparative Effectiveness Reviews, No. 7.
Gartlehner G, Hansen RA, Thieda P, et al.

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