Clinical Question

Is extended-release bupropion (Wellbutrin XL) more effective than placebo for preventing symptoms of seasonal affective disorder (SAD) in adults?

Evidence-Based Answer

When started in the fall, extended-release bupropion, 300 mg once daily, is effective in preventing recurrent symptoms in high-risk adults with a history of SAD (number needed to treat [NNT] = 5), as well as those at lower risk (NNT = 8). Headaches, nausea, and insomnia may limit adherence to treatment.¹ (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

SAD is a recurrent depressive disorder that occurs only during a particular season, typically the winter months.² SAD is more common at northern latitudes; the prevalence is estimated at 9% in the northern United States,³ and two-thirds of patients experience the symptoms every year.⁴ Preventive measures are of particular interest for this group of patients.

The authors of this Cochrane review sought studies that compared any second-generation antidepressant with placebo, other medications, or other therapies for the prevention of episodes of SAD.¹ They found only three randomized trials, each comparing extended-release bupropion with placebo. The studies enrolled a total of 1,100 patients with a history of SAD at 151 sites in Canada and the northern United States. Patients were excluded if they had medical problems or any other psychiatric illnesses, including major depression. Treatment began between the months of September and November with extended-release bupropion, 150 mg daily, titrated to 300 mg daily for those who were able to tolerate it. In all three studies, the dosage was weaned to 150 mg per day in the first week of spring and then subsequently stopped.

Participants with confirmed SAD were asymptomatic at the start of all three studies. The primary outcome in two studies was the time to onset of depressive symptoms. In the third study, the primary end point was the difference in depression-free participants between the treatment and placebo groups at the end of the study. Depressive symptoms were measured using the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders (SIGH-SAD). The studies did not address the severity of SAD symptoms, quality of life, or quality of interpersonal/social functioning. Although this review did not specify how risk of recurrence was calculated, investigators considered the number of previous episodes of SAD and a patient-reported history of pattern and symptom severity using the Seasonal Pattern Assessment Questionnaire. Extended-release bupropion prevented episodes of SAD in some patients; its effectiveness increased with higher risk of recurrence. Patients with a 50% risk of episode recurrence were more likely to benefit from therapy (NNT = 5; 95% confidence interval [CI], 4 to 7) than patients with a 30% risk of recurrence (NNT = 8; 95% CI, 6 to 12).

Adverse effects were more common in participants taking extended-release bupropion and included headache (number needed to harm [NNH] = 15; 95% CI, 8 to 75), insomnia (NNH = 16; 95% CI, 9 to 56), and nausea (NNH = 20; 95% CI, 11 to 72). However, the overall discontinuation rate from adverse effects was not significantly different between treatment and placebo groups. None of the included studies compared extended-release bupropion with nonpharmacologic therapies, including light therapy or psychotherapy. The studies also did not compare extended-release bupropion with other antidepressants. The three studies were sponsored by the pharmaceutical company that manufactures extended-release bupropion.

The United States does not currently have formal guidelines for the treatment or prevention of SAD. The Canadian Consensus Guidelines for the Treatment of Seasonal Affective Disorder discuss pharmacologic and nonpharmacologic treatment options.⁵ However, well-designed trials directly comparing pharmacologic with nonpharmacologic options are lacking. When using extended-release bupropion for the prevention of SAD, the possibility of adverse effects should be considered in a shared decision-making process between physician and patient.

The practice recommendations in this activity are available at http://www.cochrane.org.