Pleasurable sexual activity is an essential component of many human relationships, providing a sense of physical, psychological, and social well-being. Epidemiological and clinical studies show that depressive symptoms and depressive illness are associated with impairments in sexual function and satisfaction, both in untreated and treated patients. The findings of randomized placebo-controlled trials demonstrate that most of the currently available antidepressant drugs are associated with the development or worsening of sexual dysfunction, in a substantial proportion of patients. Sexual difficulties during antidepressant treatment often resolve as depression lifts but can endure over long periods and may reduce self-esteem and affect mood and relationships adversely. Sexual dysfunction during antidepressant treatment is typically associated with many possible causes, but the risk and type of dysfunction vary with differing compounds and should be considered when making decisions about the relative merits and drawbacks of differing antidepressants. A range of interventions can be considered when managing patients with sexual dysfunction associated with antidepressants, including the prescription of phosphodiesterase-5 inhibitors, but none of these approaches can be considered “ideal.” As treatment-emergent sexual dysfunction is less frequent with certain drugs, presumably related to differences in their pharmacological properties, and because current management approaches are less than ideal, a reduced burden of treatment-emergent sexual dysfunction represents a tolerability target in the development of novel antidepressants. 1. Introduction Systematic reviews of the epidemiology of sexual difficulties, dysfunction, and dissatisfaction indicate that sexual problems are common in men and women in all societies and more frequent in older individuals and among those with chronic medical conditions, including depression [1, 2]. For example, the Global Survey of Sexual Attitudes and Behavior, of over 27,000 men and women aged 40–80 years, found “early ejaculation” (i.e., rapid or premature ejaculation) to be the most common sexual dysfunction, affecting 14% of men, with “erectile difficulties” having a prevalence of 10% all sexual dysfunctions in men being more prevalent in older groups [3]. The Men’s Attitudes to Life Events and Sexuality Study, of similar size but among men aged 20–75 years, found the prevalence of “erectile dysfunction” to be 16%, the proportion being higher in older men and individuals with cardiovascular disease, hypertension, or
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