CRD Summary: This review found that s-adenosyl-l-methionine was superior to placebo and as effective as tricyclic antidepressant medication. Limitations in the analysis mean that the author’s conclusions should be treated with caution.

CRD Commentary: Inclusion criteria for the participants, intervention and study design were clearly defined.  Restricting outcomes to studies using the HAM-D might have resulted in relevant studies being omitted. Only studies with a short-term follow-up were included, which means that any conclusions can only be interpreted in light of this relatively brief timeframe. Attempts were made to identify unpublished data, but only one database was used to search for studies and it is unclear whether any language restrictions were imposed. Relevant studies might therefore have been missed and bias introduced. There was insufficient information about the study selection and data extraction processes to rule out the possibility of bias and error. Although a formal quality assessment was not undertaken, only double-blind RCTs were included; all included studies were therefore of a relatively high quality and are likely to have produced reliable results.

There was insufficient information on the characteristics of the included studies to determine the extent to which the findings can be generalised. The methods used to synthesise the studies were confusing and, in some cases, inappropriate. The author summed data across individual study arms, which ignores the randomisation in the included studies and so is not an appropriate method of analysis. The use of effect sizes was confusing; the use of standard methods of meta-analysis based on relative risks would have been easier for the reader to interpret. There was evidence of statistically significant heterogeneity for some meta-analyses and these analyses should therefore be interpreted with caution. Limitations in the analysis mean that the author’s conclusions should be treated with caution.