Table 1 Clinical trials of new therapeutic drugs for MDD
From: Major depressive disorder: hypothesis, mechanism, prevention and treatment
Study | Duration | Mean age (SD) in years | Mood disorder type | Diagnostic tool | Interventions | Control | Outcome indicators | Blinding of participants | Outcomes |
|---|---|---|---|---|---|---|---|---|---|
Fava M et al.478 | 7 days | NR | MED, with an inadequate response to one to three courses of antidepressant treatment | DSM-5; HAMD | (1) REL-1017 75 mg (Day 1), 25 mg/day (Days 2-7) (2) REL-1017 100 mg (Day 1), 50 mg/day (Days 2-7) | Placebo | MADRS; SDQ; CGI-S; CGI-I | Double blind | REL-1017 may have rapid and sustained antidepressant effects in patients with inadequate response to antidepressant treatment. |
De Martin S et al.479 | 10 days | 39 (8) | Healthy | / | REL-1017 25 mg | Placebo | BDNF plasma levels; systolic BP; diastolic BP | Double blind | Administration of 25 mg of REL-1017 significantly increased BDNF plasma levels and significantly decreased diastolic blood pressure. |
Hochschild A et al.481 | 2 days | 38.4 (13.2) | MDE, unipolar depression | DSM-IV; HAMD-17; SSI | Ketamine 0.5 mg/kg | Midazolam 0.02 mg/kg | SSI; HAMD-24; POMS; BDI | Double blind | Ketamine resulted in greater improvements in HDRS, HDRS, BDI and POMS scores and reduced suicidal ideation in patients. |
Daly EJ et al.484 | 10 weeks, with an additional 8 weeks of post-treatment follow-up | 44.7 (10.0) | TRD | DSM-IV-TR | Esketamine 28 mg, 56 mg, or 84 mg twice weekly | Placebo, an inactive substance | MADRS | Double blind | Antidepressant effects of intranasal esketamine in the treatment of TRD are rapid and dose-related. |
Abbasi SH et al.488 | 6 weeks | NR | MDD | DSM-IV-TR; HAMD-17 | Celecoxib 200 mg twice daily plus sertraline 200 mg/day | Placebo plus sertraline 200 mg/day | HAMD; IL-6 concentrations in the sera | Double blind | The serum IL-6 concentration in the celecoxib group was significantly reduced, which may be related to its antidepressant activity and can be used as an auxiliary antidepressant drug. |
Akhondzadeh S et al.489 | 6 weeks | 34.6 (6.8) | MDD | DSM-IV-TR; HAMD | Celecoxib 400 mg/day plus fluoxetine 40 mg/day | Placebo plus fluoxetine 40 mg/day | HAMD | Double blind | Celecoxib combined with fluoxetine is more effective than fluoxetine alone in treating major depression. Celecoxib may be an effective adjunct to treatment of patients with major depressive disorder. |
Nettis MA et al.490 | 4 weeks | 47.0 (10.0) | MDD with peripheral inflammation (CRP ≥ 1 mg/L) | DSM-5; MINI; HAMD-17; levels of serum CRP | Minocycline 200 mg/day | Placebo | HAMD-17; BDI- II; CGI; PSS; SHAPS; STAI-S; STAI-T: levels of inflammatory biomarkers | Double blind | Add-on therapy with minocycline may be effective in patients with MDD in patients with low-grade inflammation and CRP ≥ 3 mg/L |
Hasebe K et al.491 | 12 weeks | 51.7 (14.4) | MDD | MINI-PLUS 5; MADRS | Minocycline 200 mg/day | Placebo | HAMA; Q-LES-Q-SF; LIFE-RIFT; PGI; CGI-I; levels of IL-6, LBP and BDNF in blood samples | Double blind | There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. |
Su KP et al.492 | 2 weeks | 53 (10) | Depression induced by IFN-α | DSM-IV | Omega-3 fatty acids: EPA 3.5 g/day or DHA 1.75 g/day | Placebo (high oleic oil) | HAMD-21; NTRS; percentage of participants with MDE induced by IFN-α | Double blind | EPA is effective in preventing depression in HCV patients receiving IFN-α. |
Berk M et al.493 | 12 weeks | 20.2 (2.6) | MDD | SCID-I/P; MADRS | Rosuvastatin 10 mg/day or aspirin 100 mg/day | Placebo | MADRS; QIDS-SR; GAD-7; CGI-I/S; PGI; Q-LES-Q-SF; SAS-SR; SOFAS | Triple blind | The addition of aspirin or rosuvastatin did not produce any beneficial effects in the treatment of depression in young adults, but rosuvastatin may have potential therapeutic role in adolescent depression. |
Meltzer-Brody S et al.494 | 3 days, with an additional 4 weeks of post-treatment follow-up | NR | PPD | SCID-I; HAMD | Brexanolone 90 μg/kg/h or brexanolone 60 μg/kg/h | Placebo | HAMD-17; CGI-I; MADRS; EPDS; PHQ; GAD-7 | Double blind | Compared with placebo, after 60 hours of intravenous infusion of brexanolone, the total HAMD score of patients with postpartum depression was significantly reduced, and the drug effect was rapid and long-lasting. |
Leal GC et al.495 | 7 days | NR | TRD; and failure to respond to at least two adequate antidepressant trials in the current episode | MINI; DSM-5; MADRS | (R)-ketamine 0.5 mg/kg | Placebo (saline solution) | MADRS; CGI-S; CGI-I | Double blind | (R)-ketamine is capable of producing rapid and potent antidepressant effects in TRD subjects. |
