Toward achieving optimal response: understanding and managing antidepressant side effects.

The safety and tolerability of antidepressants have improved considerably over the past two decades, Nevertheless, antidepressant side effects are still common and problematic. The majority of patients treated with contemporary agents experience one or more bothersome side effects. These side effects often create barriers to achieving depressive remission, as well as to preventing relapse and recurrence. Clinicians tend to underestimate the prevalence of side effects, and as many as one quarter of patients discontinue their antidepressants because of difficult-to-tolerate side effects; others may continue on antidepressant therapy but experience diminished quality of life related to troublesome side effects. This article reviews the prevalence of side effects, the impact of side effects on treatment adherence, and methodological issues including the challenge of distinguishing side effects from residual depressive symptoms, discontinuation effects, and general medical problems. In addition, we address the most common side effects such as sexual dysfunction, gastrointestinal problems, sleep disturbance, apathy, and fatigue, and offer strategies for management that may help patients achieve optimal response to pharmacotherapy.