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. 2016 Oct 10;2016(10):CD011286. doi: 10.1002/14651858.CD011286.pub2

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%).