Seasonal Affective Disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occur during autumn or winter and remit in spring. Second-generation antidepressants (SGAs) are established interventions to treat acute episodes of SAD. However, little is known about the efficacy and potential harms of these interventions for preventing SAD.

To assess the efficacy and safety of SGAs to prevent SAD and improve patient–centered outcomes in adults with a history of SAD.

We searched the Cochrane Depression, Anxiety and Neuorosis Review Group's specialised register, EMBASE, MEDLINE, PsycINFO and the Cochrane Central Register of Controlled Trials. In addition, we searched pharmaceutical industry trials registers via the Internet to identify unpublished trial data. We also conducted grey literature searches and handsearches of pertinent reference lists. Two authors reviewed the evidence, abstracted data, and assessed risk of bias. We pooled data for meta-analysis when participant groups were similar and the studies assessed the same treatments with the same comparator.

We did not find eligible studies for most comparisons. We included three RCTs comparing bupropion XL with placebo. Statistically significantly fewer patients treated with bupropion experienced the onset of a major depressive episode during winter months. The overall risk of adverse events was similar between treatment groups. However, bupropionn-treated patients had significantly higher risk for headache, insomnia, and nausea.

The evidence base on SGA treatment to prevent SAD is limited. Future studies are needed to provide a sufficient evidence base for clinical decisionmaking.