Second‐generation antidepressants for preventing seasonal affective disorder in adults

Gerald Gartlehner, Barbara Nussbaumer, Bradley N Gaynes, Catherine A Forneris, Laura C Morgan, Angela Kaminski‐Hartenthaler, Amy Greenblatt, Jörg Wipplinger, Linda J Lux, Jeffrey H Sonis, Julia Hofmann, Megan G Van Noord, Dietmar Winkler

Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). To assess the efficacy and safety of second-generation antidepressants (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. A search of the Specialised Register of the Cochrane Depression, Anxiety and Neuorosis Review Group (CCDANCTR) included all years to 11 August 2015. The CCDANCTR contains reports of randomised controlled trials derived from EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO (1967 to date) and the Cochrane Central Register of Controlled Trials (CENTRAL). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Knowledge, The Cochrane Library and the Allied and Complementary Medicine Database (to 26 May 2014). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. For efficacy, we included randomised controlled trials on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared an SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus the same comparator intervention as monotherapy. Two review authors screened abstracts and full-text publications and assigned risk of bias ratings based on the Cochrane 'Risk of bias' tool. We resolved disagreements by consensus or by consultation with a third party. Two review authors independently extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi(2) statistic and the Cochran Q. We used the I(2) statistic to estimate the magnitude of heterogeneity and examined potential sources of heterogeneity using sensitivity analysis or analysis of subgroups. We assessed publication bias by using funnel plots. However, given the small number of component studies in our meta-analyses, these tests have low sensitivity to detect publication bias. We rated the strength of the evidence using the system developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. We identified 2986 citations after de-duplication of search results and excluded 2895 records during title and abstract reviews. We assessed 91 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 patients with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; three 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 40% and 50%, NNTBs are 6 (95% CI 5 to 9) and 5 (95% CI 4 to 7), 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, four of five patients 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 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.