. 2024 Feb 9;9:30. doi: 10.1038/s41392-024-01738-y

Table 1.

Clinical trials of new therapeutic drugs for MDD

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.

SD standard deviation, NR not reported, MDE major depressive episode, DSM Diagnostic and Statistical Manual of Mental Disorders, HAMD Hamilton Depression Scale, MADRS Montgomery-Asberg Depression Rating Scale, SDQ Symptoms of Depression Questionnaire, CGI-S Clinical Global Impressions Severity Scale, CGI-I Clinical Global Impressions Improvement Scale, BDNF brain-derived neurotrophic factor, BP blood pressure, SSI Beck Scale for Suicidal Ideation, POMS Profile of Mood States, BDI Beck Depression Inventory, TRD treatment resistant depression, MDD major depressive disorder, IL-6 interleukin-6, CRP C-reactive protein, MINI Mini International Neuropsychiatric Interview, PSS Perceived Stress Scale, SHAPS Snaith–Hamilton Pleasure Scale, STAI-S Spielberger State-Trait Anxiety Rating Scale-State, STAI-T Spielberger State-Trait Anxiety Rating Scale-Trait, HAMA Hamilton Anxiety Scale, Q-LES-Q-SF Quality of Life Enjoyment and Satisfaction Questionnaire Short Form, LIFE-RIFT Range of Impaired Functioning Tool, PGI Patient Global Impression, LBP lipopolysaccharide binding protein, IFN interferon, EPA eicosapentaenoic acid, DHA docosahexaenoic acid, NTRS Neurotoxicity Rating Scale, SCID Structured Clinical Interview, QIDS-SR Quick Inventory of Depression Symptomatology–Self Report, GAD-7 Generalised Anxiety Disorder seven-item scale, SAS-SR Social Adjustment Scale–Self Report, SOFAS Social and Occupational Functioning Scale, PPD postpartum depression, EPDS Edinburgh Postnatal Depression Scale, PHQ Patient Health Questionnaire