Table 3.

Completed clinical trials but not published in peer-reviewed journals until September 2022

Mood disorder	Drug	Dose	Phase	Type of study	Durationa	Follow upb	NCT number	Trial design	Adjunctive treatment or monotherapy	Depressive symptoms severity scale at baseline	Population			Drug effectiveness on depressive symptoms
											N	Sex (F/M)	Age range or mean age
MDD	AV-101	1440 mg	II	Multicenter randomized double-blind placebo-controlled parallel-group Trial	2 weeks	NA	NCT03078322	2 arms AV-101 Placebo	Adjunctive treatment	HDRS-17 > 20	199	NA	18–65	Failed to improve depressive symptoms at day 15 in the MADRS (Primary outcome)
	AXS-05	45/105 mg	III	Multicenter open-label trial	12 months	NA	NCT04039022	Single arm	Monotherapy	MADRS 33	876	62%/38%	42.4	Reduction in depressive symptoms at week 6 MADRS: −21.1 (Primary outcome)
		45/105 mg	II	Multicenter open-label trial	12 months	NA	Substudy of NCT04039022 (antidepressant unresponsive patients)	Single arm	Monotherapy	MADRS 33.3	115	NA	NA	Reduction in depressive symptoms at week 6 MADRS: −19.1 (Primary outcome)
		45/105 mg	III	Multicenter open-label trial	12 months	NA	Substudy of NCT04039022 (patients with suicidal ideation)	Single arm	Monotherapy	MADRS-suicidal ideation 3.4 MADRS 36.8	37	NA	NA	Reduction in suicidal ideation at week 3 MADRS-SI: -2.8 [P = 0,001] (Primary outcome)
	Pimavanserin	34 mg	III	Multicenter randomized double-blind placebo-controlled parallel-group trials	6 weeks	NA	NCT03968159 and NCT03999918	2 arms Pimavanserin (n 148) Placebo (n 150)	Adjunctive treatment	NA	298	69.8%/30.2%	≥ 18	Failed to improve depressive symptoms at week 5 HDRS-17: −9.0 for pimavanserin vs −8.1 for placebo [P = 0.296] (Primary outcome)
	Zuranolone	50 mg	III	Multicenter randomized double-blind placebo-controlled trial	2 weeks	Day 42	NCT04442490	2 arms Zuranolone (n 27) Placebo (n 272)	Monotherapy	HDRS-17 26.8	543	66%/34%	39.7	Reduction in depressive symptoms at day 15 HDRS-17: −14.1 for ZRN vs −12.3 for placebo [P = 0.0141] (Primary outcome)
		30 mg 50 mg	III	Open-label trial	2 weeks	1 year	NCT03864614	Single arm	Monotherapy (n 421) Adjunctive treatment (n 304)	HDRS-17 25.3	725	NA	18–75	Reduction in depressive symptoms at day 15 HDRS-17: −14.9 for zuranolone 30 vs −15.9 for zuranolone 50
		50 mg	III	Randomized double-blind placebo-controlled trial	2 weeks	6 weeks	NCT04476030	2 arms Zuranolone (n 210) Placebo (n 215)	Adjunctive treatment	HDRS-17 26.8	440	NA	18–64	Reduction in depressive symptoms at day 3 HDRS-17: −8.9 for zuranolone vs −7.0 for placebo [P = 0.0004] (Primary outcome)
		20 mg 30 mg	III	Multicenter randomized double-blind placebo-controlled trial	2 weeks	Days 43–182	NCT03672175	3 arms Zuranolone 20 (n 159) Zuranolone 30 (n 166) Placebo (n 157)	Monotherapy	HDRS-17 ≥ 22	581	70.3%/29.7%	18–65	Failed to improve depressive symptoms at day 15 HDRS-17: –12.5 for zuranolone 30 vs -11.1 for placebo [P = 0.116] [d = 0.17] vs –11.5 for zuranolone 20 [P = 0.664] [d = 0.03] (Primary outcome)
	Prax-114	40 mg	II/III	Randomized double-blind placebo-controlled trial	4 weeks	2 weeks	NCT04832425	2 arms PRAX-114 Placebo	Monotherapy	HDRS-17 ≥ 23	216	NA	18–65	Failed to improve depressive symptoms at day 15 in the HDRS-17 (Primary outcome)
	Seltorexant	20 mg 40 mg	II	Multicenter randomized double-blind flexible-dose parallel-group trial	6 months	2 weeks	NCT03321526	2 arms Seltorexant (n 52) Quetiapine (extended-release) (n 52)	Adjunctive treatment	NA	104	66.3%/33.7%	18–84	Failed to improve depressive symptoms at week 12 in the MADRS
TRD	AXS-05	45/105 mg	II	Multicenter randomized double-blind placebo-controlled trial	52 weeks	0	NCT04608396	2 arms AXS-05 (n 22) Placebo (n 22)	Monotherapy	NA	44	NA	≥ 18	Delayed the time to relapse of depressive symptoms up to 52 weeks [P = 0.002] (Primary outcome)
		45/105 mg	III	Randomized double-blind active-controlled two-period trial	12 weeks	0	NCT02741791	2 arms AXS-05 (n 156) Bupropion (n 156)	Monotherapy	NA	312	NA	18–65	Failed to improve depressive symptoms at week 6 in the MADRS [P = 0.117] [d = 0.21] (Primary outcome)
		45/105 mg	II	Multicenter open-label trial	12 months	0	NCT04634669	Single arm	Monotherapy	MADRS 32.2	150	60.7%/39.3%	45.6	Reduction in depressive symptoms at 12 months MADRS: −24.5 [P < 0.001] (Primary outcome)
	Psilocybin	1 mg 10 mg 25 mg	II	Randomized double-blind controlled trial	Single treatment session	12 weeks	NCT03775200	3 arms Psilocybin 1 Psilocybin 10 Psilocybin 25	Monotherapy (PAP)	NA	233	NA	≥18	Reduction in depressive symptoms at week 3 MADRS: −6.6 Psilocybin 25 vs psilocybin 1 [P < 0.001] (Primary outcome)
PPD	Zuranolone	50 mg	III	Randomized double-blind placebo-controlled trial	2 weeks	4 weeks	NCT04442503	2 arms Zuranolone (n 97) Placebo (n 98)	Monotherapy	HDRS-17 ≥ 26	195	NA	18–45	Reduction in depressive symptoms at day 15 HDRS-17: −15.6 for zuranolone vs −11.6 for placebo [P = 0.0007] (Primary outcome)
Bipolar depression	Zuranolone	30 mg	III	Open-label trial	2 weeks	4 weeks	NCT03692910	2 arms Zuranolone Placebo	Monotherapy	HDRS 25.7	35	23%/12%	47.6	Reduction in depressive symptoms MADRS: −7.7 on day 3, -15.5 on day 15, -16.4 on day 42
PMD	Prax-114	60 mg	II	Open-label trial	2 weeks	2 weeks	NA	Single arm	Monotherapy	HDRS-17 25.3	6	100%/0%	NA	Reduction in depressive symptoms at day 15 HDRS-17: −12 (Primary outcome)

For some studies, some data is not available (i.e. follow-up, depressive symptoms severity scale at baseline, sex, age range or mean age, P value, effect size).

HDRS, Hamilton Depression Rating Scale total score; MADRS, Montgomery-Asberg Depression Rating Scale total score; MADRS-SI, Montgomery-Asberg Depression Rating Scale-Suicidal Ideation total score; MDD, major depressive disorder; NA, not available; PAP, psilocybin assisted psychotherapy; PMD, perimenopausal depression; PPD, postpartum depression; TRD, treatment-resistant depression.

^aRefers to the length over time of the pharmacological intervention.

^bRefers to the length of monitoring over time of participant’s health after the end of the pharmacological intervention.