Table 1.
Randomised controlled trials of drugs included in the systematic review and network meta-analysis
| Diagnostic criteria | Type of depression | Treatments (dose range) | Number randomly assigned to each group | Treatment duration (selected timepoint, weeks) | Age range, years (mean) | Proportion female | Area recruited from | Setting | Baseline severity scale; mean baseline severity (SD) | Transforming score of baseline*(SD) | Manufacturer funder | Type of publication | Type of blinding | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Kye et al (1996) | K-SADS and RDC | MDD | Amitriptyline (5 mg/day per kg); pill placebo | 18/13 | 8 (8) | 12–17 (14·8) | 29% | USA | Outpatients | HAMD (clinician-reported); 12·50 (4·31) | 41·73 (8·52) | None | Published trial | Double-blind |
| Von Knorring et al (2006) | DSM-IV | MDD | Citalopram (10–40 mg/day); pill placebo | 124/120 | 12 (12) | 13–18 (16·0) | Not stated | Europe | Inpatients and outpatients | MADRS (clinician-reported); Not stated | Not stated | Lundbeck | Unpublished data from author | Double-blind |
| Wagner et al (2004) | DSM-IV | MDD | Citalopram (20–40 mg/day); pill placebo | 93/85 | 8 (8) | 7–17 (12·1) | 53% | USA | Not stated | CDRS-R (clinician-reported); 58·32 (10·98) | 58·32 (10·98) | Forest Laboratories | Published trial | Double-blind |
| Braconnier et al (2003) | DSM-IV | MDD | Clomipramine (75–150 mg/day); Paroxetine (20–40 mg/day) | 58/63 | 8 (8) | 12–20 (16·1) | 60% | France | Not stated | MADRS (clinician-reported); 31·84 (4·63) | 65·29 (7·02) | GlaxoSmithKline | Published trial | Double-blind |
| Klein et al (1998) | DSM-III-R | MDD | Desipramine (50–300 mg/day); pill placebo | 23/22 | 6 (6) | 13–18 (15·7) | 67% | USA | Outpatients | HAMD-24 (clinician-reported); 21·39 (4·44) | 42·61 (5·32) | None | Published trial | Double-blind |
| Kutcher et al (1994) | DSM-III-R | MDD | Desipramine (200 mg/day); pill placebo | 30/30 | 6 (6) | 15–19 (17·8) | 70% | Canada | Outpatients | HAMD (clinician-reported); 23·20 (5·23) | 57·60 (9·15) | None | Published trial | Double-blind |
| Atkinson et al (2018) | DSM-IV-TR | MDD | Desvenlafaxine (20–35 mg/day); Desvenlafaxine (25–50 mg/day); pill placebo | 122/121/120 | 8 (8) | 7–17 (13·0) | 56% | USA and Chile | Outpatients | CDRS-R (clinician-reported); 58·09 (9·19) | 58·09 (9·19) | Pfizer | Published trial | Double-blind |
| Weihs et al (2018) | DSM-IV-TR | MDD | Desvenlafaxine (25–50 mg/day); Fluoxetine (20 mg/day); pill placebo | 115/113/112 | 8 (8) | 7–17 (12·7) | 54% | USA and Mexico | Outpatients | CDRS-R (clinician-reported); 56·53 (8·94) | 56·53 (8·94) | Pfizer | Published trial | Double-blind |
| Emslie et al (2014) | DSM-IV-TR | MDD | Duloxetine (60 mg/day); Duloxetine (30 mg/day); Fluoxetine (20 mg/day); pill placebo | 108/116/117/122 | 10 (10) | 7–17 (13·0) | 51% | Cross-continental | Outpatients | CDRS-R (clinician-reported); 58·78 (10·33) | 58·78 (10·33) | Eli Lilly | Published trial | Double-blind |
| Atkinson et al (2014) | DSM-IV-TR | MDD | Duloxetine (60–120 mg/day); Fluoxetine (20–40 mg/day); pill placebo | 117/117/103 | 10 (10) | 7–17 (13·2) | 52% | Cross-continental | Outpatients | CDRS-R (clinician-reported); 59·37 (10·90) | 59·37 (10·90) | Eli Lilly | Published trial | Double-blind |
| Emslie et al (2009) | DSM-IV | MDD | Escitalopram (10–20 mg/day); pill placebo | 158/158 | 8 (8) | 12–17 (14·6) | 59% | USA | Outpatients | CDRS-R (clinician-reported); 56·80 (8·26) | 56·80 (8·26) | Forest Laboratories | Published trial | Double-blind |
| Wagner et al (2006) | DSM-IV | MDD | Escitalopram (10–20 mg/day); pill placebo | 132/136 | 8 (8) | 6–17 (12·3) | 52% | USA | Outpatients | CDRS-R (clinician-reported); 55·57 (Not stated) | 55·57 (Not stated) | Forest Laboratories | Published trial | Double-blind |
| Attari et al (2006) | DSM-IV | MDD | Fluoxetine (0·5–2 mg/day per kg); Nortriptyline (1–2 mg/day per kg) | 20/20 | 8 (8) | 7–16 (12·9) | 50% | Iran | Outpatients | CDI (self-reported); 28·65 (8·50) | 65·28 (14·33) | Not stated | Published trial | Double-blind |
| Almeida-Montes et al (2005) | DSM-IV-TR | MDD | Fluoxetine (20 mg/day); pill placebo | 12/11 | 6 (6) | 8–14 (11·4) | 35% | Mexico | Outpatients | DSRS (self-reported); Not stated | Not stated | None† | Published trial | Double-blind |
| Eli Lilly et al (1986) | DSM-III | MDD | Fluoxetine (20–60 mg/day); pill placebo | 21/19 | 6 (6) | 12–17 (15·6) | 55% | Canada | Inpatients and outpatients | HAMD-17 (clinician-reported); 21·90 (3·46) | 55·33 (6·06) | Eli Lilly | Unpublished trial from Eli Lilly company | Double-blind |
| Emslie et al (1997) | DSM-III-R | MDD | Fluoxetine (20 mg/day); pill placebo | 48/48 | 8 (8) | 7–17 (12·4) | 46% | USA | Outpatients | CDRS-R (clinician-reported); 58·05 (10·40) | 58·05 (10·40) | None | Published trial | Double-blind |
| Emslie et al (2002) | DSM-IV | MDD | Fluoxetine (10–20 mg/day); pill placebo | 109/110 | 9 (9) | 8–18 (12·7) | 49% | USA | Outpatients | CDRS-R (clinician-reported); 56·10 (10·92) | 56·10 (10·92) | Eli Lilly | Published trial | Double-blind |
| Findling et al (2009) | DSM-IV | MDD or other depressive disorder | Fluoxetine (10–20 mg/day); pill placebo | 18/16 | 8 (8) | 12–17 (16·5) | 15% | USA | Outpatients | CDRS-R (clinician-reported); 53·44 (9·70) | 53·44 (9·70) | Eli Lilly | Published trial | Double-blind |
| Hongfen et al (2009) | CCMD-3 | MDD | Fluoxetine (20 mg/day); Venlafaxine (150 mg/day) | 30/30 | 8 (8) | 12–18 (15·8) | 47% | China | Inpatients and outpatients | HAMD-17 (clinician-reported); 22·05 (2·34) | 55·59 (4·10) | Not stated | Unpublished trial from abstract for conference | Double-blind |
| Puig-Antich et al (1987) | K-SADS and RDC | MDD | Imipramine (3·25–5 mg/day per kg); pill placebo | 20/22 | 5 (5) | 6–12 (9·1) | 40% | USA | Inpatients and outpatients | K-SADS-9 (clinician-reported); 3·05 (0·56) | Not available | None | Published trial | Double-blind |
| Organon et al (2002) | DSM-IV | MDD | Mirtazapine (15–45 mg/day); pill placebo | 82/44 | 8 (8) | 7–18 (12·3) | 51% | Europe | Outpatients | CDRS-R (clinician-reported); 51·28 (9·05) | 51·28 (9·05) | Organon | Unpublished trial from FDA report | Double-blind |
| Organon et al (2002) | DSM-IV | MDD | Mirtazapine (15–45 mg/day); pill placebo | 88/45 | 8 (8) | 7–18 (12·0) | 53% | Europe | Outpatients | CDRS-R (clinician-reported); 48·43 (10·56) | 48·43 (10·56) | Organon | Unpublished trial from FDA report | Double-blind |
| Bristol-Myers Squibb (2002) | DSM-IV | MDD | Nefazodone (100–300 mg/day); Nefazodone (200–600 mg/day); pill placebo | 95/95/94 | 8 (8) | 7–17 (Not stated) | Not stated | Not stated | Not stated | CDRS-R (clinician-reported); 60·17 (Not stated) | 60·17 (Not stated) | Bristol-Myers Squibb | Unpublished trial from FDA report | Double-blind |
| Emslie et al (2002) | DSM-IV | MDD | Nefazodone (100–400 mg/day); pill placebo | 99/96 | 8 (8) | 12–17 (Not stated) | 59% | Not stated | Not stated | CDRS-R (clinician-reported); Not stated | Not stated | Bristol-Myers Squibb | Unpublished trial from abstract for conference | Double-blind |
| Geller et al (1990) | DSM-III | MDD | Nortriptyline (45–140 mg/day); pill placebo | 12/19 | 8 (8) | 12–17 (14·3) | 45% | USA | Outpatients | CDRS (clinician-reported); 51·36 (3·91) | 51·36 (3·91) | None | Published trial | Double-blind |
| Geller et al (1992) | DSM-III | MDD | Nortriptyline (10–140 mg/day); pill placebo | 30/30 | 8 (8) | 6–12 (9·7) | 30% | Not stated | Outpatients | CDRS-R (clinician-reported); 49·75 (4·37) | 49·75 (4·37) | None | Published trial | Double-blind |
| Berard et al (2006) | DSM-IV | MDD | Paroxetine (20–40 mg/day); pill placebo | 187/99 | 12 (8) | 13–18 (15·6) | 67% | Cross-continental | Outpatients | MADRS (clinician-reported); 25·90 (6·42) | 56·28 (9·74) | GlaxoSmithKline | Published trial | Double-blind |
| Emslie et al (2006) | DSM-IV | MDD | Paroxetine (10–50 mg/day); pill placebo | 104/102 | 8 (8) | 7–17 (12·0) | 47% | USA and Canada | Not stated | CDRS-R (clinician-reported); 61·64 (9·20) | 61·64 (9·20) | GlaxoSmithKline | Published trial | Double-blind |
| GlaxoSmithKline (2009) | DSM-IV-TR | MDD | Paroxetine (10–40 mg/day); pill placebo | 29/27 | 8 (8) | 7–17 (14·6) | 61% | Japan | Not stated | CDRS-R (clinician-reported); 56·08 (7·84) | 56·08 (7·84) | GlaxoSmithKline | Unpublished trial from clinical trials.gov | Double-blind |
| Noury et al (2015) | DSM-III-R | MDD | Paroxetine (20–60 mg/day); Imipramine (200–300 mg/day); pill placebo | 93/95/87 | 8 (8) | 12–18 (14·9) | 62% | USA | Not stated | HAMD-17 (clinician-reported); 18·66 (4·19) | 49·65 (7·33) | None | Published trial | Double-blind |
| Wagner et al (2003) | DSM-IV | MDD | Sertraline (50–200 mg/day); pill placebo | 97/91 | 10 (10) | 6–17 (Not stated) | 51% | Cross-continental | Outpatients | CDRS-R (clinician-reported); 64·01 (10·97) | 64·01 (10·97) | Pfizer | Published trial | Double-blind |
| Wagner et al (2003) | DSM-IV | MDD | Sertraline (50–200 mg/day); pill placebo | 92/96 | 10 (10) | 6–17 (Not stated) | 52% | Cross-continental | Outpatients | CDRS-R (clinician-reported); 64·91 (10·98) | 64·91 (10·98) | Pfizer | Published trial | Double-blind |
| Emslie et al (2007)‡ | DSM-IV | MDD | Venlafaxine (37·5–225 mg/day); pill placebo | 184/183 | 8 (8) | 7–17 (12·3) | 46% | USA | Outpatients | CDRS-R (clinician-reported); 56·10 (8·80) | 56·10 (8·80) | Wyeth Research | Unpublished data from author | Double-blind |
| Durgam et al (2018) | DSM-IV-TR | MDD | Vilazodone (15 mg/day); Vilazodone (30 mg/day); pill placebo | 175/180/174 | 8 (8) | 12–17 (14·8) | 60% | USA | Outpatients | CDRS-R (clinician-reported); 57·36 (8·59) | 57·36 (8·59) | Forest Research Institute | Published trial | Double-blind |
References for included studies are provied in the appendix (pp 41–48). CCMD-3=Chinese Classification of Mental Disorders third version. CDI=Children's Depression Inventory. CDRS-R=Children's Depression Rating Scale-Revised. DSRS=Depression Self-Rating Scale. FDA=US Food and Drug Administration. HAMD=Hamilton Rating Scale for Depression. K-SADS=Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children. MADRS=Montgomery-Asberg Depression Rating Scale. MDD=major depressive disorder. RDC=Research Diagnostic Criteria.
*
The method for transforming other depressive scales to CDRS-R.26
†
The authors stated that fluoxetine and placebo were donated by Eli Lilly, but this company was not involved in the design, planning, implementation, collection, analysis, and presentation of the results of this study.
‡
This publication reports the combined data from two similarly designed controlled studies comparing venlafaxine with placebo.