Barriers to achieving treatment goals: A focus on sleep disturbance and sexual dysfunction

Background: Patients who meet the criteria for a major depressive episode experience a constellation of symptoms, and different symptom configurations may reflect distinct underlying neurological disturbances. Similarly, the differing receptor profiles of the various antidepressants may explain relatively low remission rates and persistent symptoms even after remission. In particular, depressed patients frequently display altered circadian rhythms, sleep disturbances, and diurnal mood variation. Exploring treatments that can restore mood while having a positive impact on circadian rhythms and sleep would greatly improve the ability to treat this core features of depression. Methods: The mechanisms of action of the various classes of antidepressants, their effects on sleep and issues beyond sleep, including sexual dysfunction, are explored, along with questions relating to adherence. Results: Unfortunately, persistent sleep problems are among the most difficult-to-treat residual symptoms of depression. Many of the currently available antidepressants have adverse effects on circadian processes, including sleep, and may actually worsen sleep problems. Tolerability is also an enduring issue; SSRI and SNRI antidepressants are associated with central nervous sysytem and gastrointestinal effects, sexual side effects and suicidality. Improved drug tolerability would not only minimize distressing adverse effects, but would also improve adherence, thus maximizing the chances of successful treatment. Conclusions: The complexity of managing a major depressive episode is well illustrated by sleep disturbance and sexual dysfunction, two core symptoms of MDD that may also be caused or exacerbated by antidepressant therapy. Future antidepressants should alleviate symptoms without adversely affecting sleep or sexual function.