Table 2.

Summary of efficacy and tolerability data

Study	SAMe sample	Control sample	MD SAMe	MD control	Efficacy	Side effects	Response method	Response rate SAMe	Response rate control
Caruso 1984 [36]	25	24	11.4 (7.7)	2.9 (6.4)	SAMe better than placebo	Not reported	NR	NR	NR
Kagan 1990 [37]	9	6	16.2 (6.9)	7.3 (14.3)	SAMe better than placebo	Mild side effects only, resolved spontaneously	NR	NR	NR
Berlanga 1992 [38]	20	20	13.7 (4.6)	9.6 (6.2)	SAMe + IMI better than placebo + IMI	Typical anticholinergic effects of IMI (mild). Mild weight gain	Reduction HAM ≥ 50%	65	45
Papakostas 2010 [39] *	24	31	11.1 (6.1)	15.8 (6.2)	SAMe + SRI better than placebo + SRI	Slightly higher mean supine systolic blood pressure in the treatment group	Reduction HAM ≥ 50%	75.0	12.9
Delle Chiaie 2002a [40]	143	135	12.6 (8.1)	13.1 (8.6)	SAMe equal to imipramine	Dry mouth, constipation, and tachycardia. More frequent IMI	Reduction HAM ≥ 50%	51	57
Delle Chiaie 2002b [40]	146	147	12.6 (8.0)	13.1 (7.1)	SAMe equal to imipramine		Reduction HAM ≥ 50%	58.9	50.3
Mischoulon 2014a [41]	36	31	6.19 (7.38)	5.11 (6.92)	SAMe equal to placebo	Good tolerability. GI complaints	Reduction HAM ≥ 50%	35	30
Mischoulon 2014b [41]	36	30	6.19 (7.38)	6.31 (6.98)	SAMe equal to escitalopram		Reduction HAM ≥ 50%	35	34
Sarris 2014a [42]	18	16	7.31 (5.96)	4.0 (5.6)	SAMe better than placebo	Interventions were well tolerated with no significant adverse effects	Reduction HAM ≥ 50%	45	26
Sarris 2014b [42]	18	20	7.31 (5.96)	6.69 (5.7)	SAMe equal to escitalopram		Reduction HAM ≥ 50%	45	31
Sarris 2018 [43]	37	39	11.4 (7.54)	12.1 (7.02)	SAMe equal to placebo	Irritability, hot/cold flashes, cramping, confusion, headache, vertigo/dizziness, twitching, sleep difficulty and fatigue	Reduction MADRS ≥ 50%	54.3	50

NR not reported, MD mean difference