Summary of findings 3. S‐adenosyl methionine as monotherapy compared to SSRI antidepressant agent as monotherapy for depression in adults.

S‐adenosyl methionine compared to SSRI antidepressant agent as monotherapy for depression in adults
Patient or population: adults with depression Settings: outpatients Intervention: SAMe as monotherapy Comparison: SSRI antidepressant agent as monotherapy
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	SAMe vs. SSRI antidepressant agent as monotherapy
Efficacy. Change in scores from baseline to end of treatment on the depression rating scale A larger negative MD indicates greater improvement in the SAMe group Follow‐up: 12 weeks	‐	The mean change in scores from baseline to end of treatment on the depression rating scale in the SAMe group was 0.12 standard deviations lower (2.75 lower to 2.99 higher), indicating less improvement. However, this was not statistically significant	‐	129 (1 study)	⊕⊕⊝⊝ low1,2	MD 0.12 (95% CI ‐2.75 to 2.99)
Acceptability Participants dropping out of treatment during the study period for any reason Follow‐up: 12 weeks	Study population		RR 0.81 (0.57 to 1.16) not statistically significant	129 (1 study)	⊕⊕⊝⊝ low3,4	‐
	54 per 100	44 per 100 (31 to 62)
	Moderate
	54 per 100	44 per 100 (31 to 63)
Proportions of participants responding to treatment ≥ 50% reduction in depression score from baseline to end of treatment A larger RR indicates greater response to treatment in the SAMe group Follow‐up: 12 weeks	Study population		RR 1.06 (0.66 to 1.7) not statistically significant	129 (1 study)	⊕⊕⊝⊝ low3,4	‐
	34 per 100	36 per 100 (22 to 58)
	Moderate
	34 per 100	36 per 100 (22 to 58)
Proportions of participants achieving remission depression rating scale score within the normal range at the end of the study A larger RR indicates greater response to treatment in the SAMe group Follow‐up: 12 weeks	Study population		RR 1.02 (0.58 to 1.77) not statistically significant	129 (1 study)	⊕⊕⊝⊝ low3,4	‐
	28 per 100	28 per 100 (16 to 49)
	Moderate
	28 per 100	28 per 100 (16 to 49)
Acceptability. Participants experiencing troublesome adverse effects of any nature	No data	‐	‐	‐	‐	‐
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; MD: mean difference; RR: risk ratio; SAMe: S‐adenosyl methionine; SSRI: selective serotonin reuptake inhibitor.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

¹ downgraded one point because of imprecision caused by small sample size, fewer than 400.
 ² downgraded one point because of imprecision caused by a 95% confidence interval that included no effect and the upper and lower confidence limit crossed an effect size of 0.5 in either direction.
 ³ downgraded one point because of imprecision caused by a total number of events that was fewer than 300.
 ⁴ downgraded one point because of imprecision caused by a 95% confidence interval that includes both no effect and appreciable benefit and appreciable harm (the threshold for 'appreciable benefit' or 'appreciable harm' was a relative risk reduction (RRR) or relative risk increase (RRI) greater than 25%).