Abstract: We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.

Plain-language summary: In populations with a high risk of developing a new depressive episode in the next winter, results show that antidepressants can prevent winter depression in about one in four people. In populations with a lower risk of recurrence, antidepressants can prevent a new depressive episode in one of eight people. The other seven people suffer from winter depression despite treatment or would not have suffered from winter depression anyway. People using antidepressants are at slightly higher risk of experiencing headaches, nausea or insomnia when compared with people not taking antidepressants. Doctors need to discuss with patients the advantages and disadvantages of antidepressants and other potentially preventive treatments for winter depression, such as light treatment, psychological therapies or lifestyle interventions. As no available studies have compared these treatments, the decision for or against preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Review authors recommend that future studies should directly compare antidepressants against other treatments, such as light therapy, psychological therapies or other drugs to determine the best treatment for preventing winter depression.