Table 1. Clinical trials included in the systematic review of antidepressant activity of anti-cytokine treatment.
| Study | Design | Drug (n) | Placebo/comparison group (n) | Main outcome | Drug target | Dosage | Study duration | Assessment of depressive symptoms |
Change in mean depression score from baselinea |
CONSORT score (%) | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment group | Placebo/comparison group | ||||||||||
| RCTs of anti-cytokine drug vs placebo | |||||||||||
| Tyring et al. (2006)27 | Double-blind RCT | Etanercept (305) | Placebo (292) | Psoriasis | TNF-α | 50 mg twice weekly | 12 weeks | BDI | −3.9 | −2.1 | 94% |
| Loftus et al. (2008)35 (weeks 4–56) | Double-blind RCT | Adalimumab (324) | Placebo (168) | Crohn’s Disease | TNF-α | 40 mg weekly or every other week | 52 weeks | ZDS | −1.1 | +1.8 | 53% |
| Langley et al. (2010)47 | Double-blind RCT | Ustekinumab (800) | Placebo (398) | Psoriasis | IL-12, 23 | 45/90 mg at weeks 0,4; then every 12 weeks | 12 weeks | HADS-D | −1.9 | +0.2 | 52% |
| Menter et al. (2010)46 | Double-blind RCT | Adalimumab (44) | Placebo (52) | Psoriasis | TNF-α | 40 mg every other week | 12 weeks | ZDS | −6.7 | −1.6 | 56% |
| Tyring et al. (2013)26 | Double-blind RCT | Etanercept (59) | Placebo (62) | Psoriasis | TNF-α | 50 mg twice weekly | 12 weeks | PROMIS depression score | −5.5 | −2.7 | b |
| Raison et al. (2013)20 | Double-blind RCT | Infliximab (27) | Placebo (28) | Treatment-resistant depression | TNF-α | 5 mg kg−1 at weeks 0, 2 and 6 | 12 weeks | HAM-D | −7.5 | −9.6 | 91% |
| Simpson et al. (2015)45 | Double-blind RCT | Dupilumab (318) | Placebo (61) | Atopic dermatitis | IL-4 R-α | Variable (100 to 600 mgs every 1–4 weeks) | 16 weeks | HADS | −4.2 | +0.1 | b |
| RCTs of anti-cytokine drugs as adjuncts to an active treatment | |||||||||||
| Kekow et al. (2010)50 | Double-blind RCT | Etanercept+DMARD (265) | DMARD (263) | Rheumatoid arthritis | TNF-α | 50 mg weekly | 52 weeks | HADS-D | −2.4 | −2.0 | 48% |
| Bae et al. (2013)48 | Randomised open-label | Etanercept+DMARD (192) | DMARD (100) | Rheumatoid arthritis | TNF-α | 25 mg twice weekly | 16 weeks | HADS-D | −2.2 | −1.3 | 63% |
| Machado et al. (2014)49 | Randomised open-label | Etanercept+DMARD (279) | DMARD (142) | Rheumatoid arthritis | TNF-α | 50 weekly | 24 weeks | HADS-D | −2.8 | −1.9 | 77% |
| Non-randomised and/or non-placebo trials | |||||||||||
| Minderhoud et al. (2007)38 | Single-blind | Infliximab (14) | — | Crohn’s Disease | TNF-α | 5 mg kg−1 at baseline | 4 weeks | CES-D | −5.7 | — | — |
| Loftus et al. (2008)35 (weeks 0–4) | Open-label | Adalimumab (499) | — | — | TNF-α | 80 mg at baseline; 40 mg at week 2 | 4 weeks | ZDS | −9.1 | — | — |
| Gelfand et al. (2008)56 | Open-label | Etanercept (2546) | — | — | TNF-α | 50 mg twice weekly | 12 weeks | BDI | Not reported | — | — |
| Dauden et al. (2009)37 | Randomised (to dosage regimen), open-label | Etanercept (703) | — | — | TNF-α | 25 or 50 mg twice weekly | 54 weeks | HADS-D | −1.6 | — | — |
| Guh et al. (2010)51 | Open-label | Adalimumab (174) | — | — | TNF-α | 80 mg at baseline; 40 mg every other week | 24 weeks | BDI | −4.4 | — | — |
| Ertenli et al. (2012)53 | Open-label | Infliximab (16) | — | — | TNF-α | 5 mg kg−1 at weeks 0, 2 and 6 | 6 weeks | HADS-D | −3.0 | — | — |
| Gniadecki et al. (2012)36 | Randomised (to dosage regimen) double-blind | Etanercept (752) | — | — | TNF-α | 50 mg weekly; 50 mg twice weekly | 12 weeks | HADS-D | −1.5 | — | — |
| Bhutani et al. (2013)52 | Open-label | Adalimumab (32) | — | — | TNF-α | 80–40 mg every other week | 24 weeks | PGWB depression | −1.9 | — | — |
| Eisenberg et al. (2013)57 | Open-label | Eisenberg (9) | — | Complex regional pain syndrome type 1 | TNF-α | 40 mg twice every other week | 4 weeks | BDI | Not reported | — | — |
| Traki et al. (2013)54 | Open-label | Tocilizumab (26) | — | Rheumatoid arthritis | IL-6 R | 8 mg kg−1 monthly | 26 weeks | HADS-D | −1.0 | — | — |
| Gossec et al. (2015)55 | Open-label | Tocilizumab (610) | — | Rheumatoid arthritis | IL-6 R | – | – | HADS-D | −1.3 | — | — |
Abbreviations: BDI, Beck’s Depression Inventory; CES-D, Centre for Epidemiological Studies Depression Scale; DMARD, disease-modifying anti-rheumatic drug; HADS(-D), Hospital Anxiety and Depression Scale (Depression); HAM-D, Hamilton Depression Rating Scale; IL, interleukin; PGWB depression, Psychological General Well-Being depression; RCT, randomised controlled trial; TNF-α, tumor necrosis factor alpha; ZDS, Zung Depression Inventory.
a
(−)ve=decrease in depression score from baseline, (+)ve=increase in depression score from baseline.
b
Could not assess fully because articles published as a letter or as a conference abstract (data from Tyring et al. was extracted using software and from Simpson et al. by contacting authors directly).