Abstract: For efficacy we included three randomised trials of between five and eight weeks duration with a total of 204 participants. For adverse effects we included two randomised trials and three observational (non-randomised) studies of five to eight weeks duration with a total of 225 participants. Overall, the randomised trials had low-to-moderate risk of bias, and the observational studies had a high risk of bias (due to small size and high attrition). The participants in the studies all met DSM (Diagnostic and Statistics Manual of Mental Disorders) criteria for SAD. The average age was approximately 40 years and 70% of the participants were female. Results from one trial with 68 participants showed that fluoxetine was not significantly more effective than placebo in achieving clinical response (risk ratio (RR) 1.62, 95% confidence interval (CI) 0.92 to 2.83). The number of adverse effects were similar between the two groups. We located two trials that contained a total of 136 participants for the comparison fluoxetine versus light therapy. Our meta-analysis of the results of the two trials showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24), RR of remission 0.81 (95% CI 0.39 to 1.71). The number of adverse effects was similar in both groups. Two of the three randomised trials and three non-randomised studies contained adverse effect data on 225 participants who received fluoxetine, escitalopram, duloxetine, reboxetine, light therapy or placebo. We were only able to obtain crude rates of adverse effects, so any interpretation of this needs to be undertaken with caution. Between 22% and 100% of participants who received a SGA suffered an adverse effect and between 15% and 27% of participants withdrew from the studies because of adverse effects. Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo, which shows a non-significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy, which suggest equivalence between the two interventions. The lack of available evidence precludes the ability to draw any overall conclusions on the use of SGAs for SAD. Further larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs. Data on adverse events were sparse, and a comparative analysis was not possible. Therefore the data we obtained on adverse effects is not robust and our confidence in the data is limited. Overall, up to 27% of participants treated with SGAs for SAD withdrew from the studies early due to adverse effects. The overall quality of evidence in this review is very low.

Plain-language summary: We found three trials with a total of 204 participants that looked at one SGA (fluoxetine) compared with placebo or light therapy. We did not find any trials on other SGAs. One trial (68 participants) compared fluoxetine with placebo. Fluoxetine appears to work better than placebo for winter depression, but we cannot say this with certainty due to the small numbers involved in the trial. Approximately the same number of participants in both groups experienced a side effect. We found two trials (with 136 participants in total) that compared fluoxetine with light therapy. When we combined the results of these two trials we found that there was no difference between the two groups: approximately 66 people out of 100 improved in both the fluoxetine and light therapy groups. We are unsure whether this summary result is correct because the trials are small and have some problems with their design as well as a high drop-out rate (many participants did not finish the trials). About the same number of participants had side effects in the fluoxetine and light therapy groups. We found three additional studies that gave us information on the side effects of other SGAs (fluoxetine, escitalopram, duloxetine, and reboxetine), but we cannot compare the drugs directly. We can say that about 15% to 27% of people had to leave the studies early because of side effects and that the most common side effects were nausea, diarrhoea, disturbed sleep, decreased sex drive, dry mouth and agitation. We could not compare the rates of side effects in people taking SGAs compared with placebo drugs which means that our confidence in the information on side effects is limited.