Comparison 2. S‐adenosyl methionine versus tricyclic antidepressant agent as monotherapy.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Efficacy. Change in mean scores from baseline to end of treatment on depression rating scale (negative value = improvement)	4	619	Std. Mean Difference (IV, Random, 95% CI)	‐0.04 [‐0.34, 0.27]
1.1 vs. imipramine	4	619	Std. Mean Difference (IV, Random, 95% CI)	‐0.04 [‐0.34, 0.27]
2 Acceptability. Participants dropping out of treatment during study period for any reason	3	78	Risk Ratio (M‐H, Random, 95% CI)	0.61 [0.28, 1.31]
2.1 vs. imipramine	2	52	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.29, 2.39]
2.2 vs. desipramine	1	26	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.14, 1.30]
3 Acceptability. Participants dropping out of treatment during study period because of adverse effects	2	52	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.20, 2.79]
3.1 vs. imipramine	2	52	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.20, 2.79]
4 Efficacy. Response to treatment, defined as a ≥ 50% reduction in depression score from baseline to end of treatment	4	622	Risk Ratio (M‐H, Random, 95% CI)	1.14 [0.83, 1.56]
4.1 vs. imipramine	3	596	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.81, 1.44]
4.2 vs. desipramine	1	26	Risk Ratio (M‐H, Random, 95% CI)	3.00 [0.74, 12.21]
5 Acceptability. Participants experiencing troublesome adverse effects of any nature	3	604	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.52, 0.88]
5.1 vs. imipramine	3	604	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.52, 0.88]
6 Acceptability. Participants experiencing specific adverse effects: mania or hypomania	2	48	Risk Ratio (M‐H, Random, 95% CI)	3.00 [0.13, 68.26]
6.1 vs. imipramine	2	48	Risk Ratio (M‐H, Random, 95% CI)	3.00 [0.13, 68.26]
7 Acceptability. Participants dropping out for any reasons other than adverse effects	2	52	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.17, 5.89]
7.1 vs. imipramine	2	52	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.17, 5.89]