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Antidepressant-Induced Sexual Dysfunction: Five Management Strategies

Antidepressant-Induced Sexual Dysfunction: Five Management Strategies

Abstract: Selective serotonin reuptake inhibitors and other second-generation antidepressants have become common therapeutic options for the management of depression. Although these agents are effective and generally well tolerated, they frequently cause sexual adverse effects that can impact patients' quality of life, thus ultimately leading to nonadherence to therapy in many cases. Counsel patients about these possible adverse effects, and assess their sexual function at baseline and during therapy to monitor for these effects. Management strategies include watchful waiting, dosage reduction, drug holidays, switching antidepressants, and use of add-on medications.

Key words: sexual dysfunction, antidepressants, serotonin reuptake inhibitors

The American College of Physicians recommends that second-generation antidepressants (including selective serotonin reuptake inhibitors [SSRIs], serotonin norepinephrine reuptake inhibitors [SNRIs], and atypical agents) replace the classic antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors) as the standard of care for pharmacological treatment of major depressive disorder (MDD) because of their reduced toxicity and adverse-effect profiles.1 The second-generation antidepressants are equally efficacious in the treatment of MDD1; thus, the challenge is to select the best agent for the patient. A complete evaluation should include potential adverse effects and consequent impact on quality of life.

Sexual dysfunction is an adverse effect of antidepressants that occurs in about 20% to 45% of treated patients, depending on the antidepressant used.2 Dysfunction presents as alterations in one or more sexual phases, and antidepressants can affect all phases of sexual function.3 Common dysfunctions include reduced libido, erectile or vaginal dysfunction, delayed orgasm, and anorgasmia.3 Further complicating the problem is that the sexual phases can have varying degrees of dysfunction.

The onset and duration of sexual dysfunction may vary between patients as a result of their medical and sexual history; thus, tracking any changes in sexual function after the initiation of treatment is crucial. If antidepressant therapy is not well tolerated because of sexual adverse effects, nonadherence may result, potentially leading to relapse or recurrence of depressive symptoms.2

In this article, we present 5 strategies that can be used to manage antidepressant-induced sexual dysfunction.


Numerous neurotransmitter systems are critical for normal sexual function, including the serotonin, dopamine, acetylcholine, and norepinephrine receptors4,5:

Serotonin (5-HT): activation of the 5-HT2A receptor inhibits sexual responses.
Dopamine: enhances libido.
Acetylcholine: facilitates erection and lubrication.
Norepinephrine: regulates the processes of erection and orgasm.


Because antidepressants target these neurotransmitter systems, they can alter sexual functioning. Although sexual dysfunction has been attributed to a number of antidepressant classes, the SSRIs, which are highly serotonergic, appear to be most likely to cause sexual dysfunction.2 Indeed, about 30% to 60% of patients who receive SSRI therapy experience these adverse effects.2 In contrast, bupropion, nefazodone, and mirtazapine are associated with much lower rates of sexual dysfunction,6 presumably because of 5-HT2 receptor antagonism (nefazodone and mirtazapine) or absence of serotonin reuptake inhibition (bupropion).


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