Evidence-Based Reviews

Sex and antidepressants: When to switch drugs or try an antidote

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Help patients stay on depression treatment by reducing sexual side effects



Antidepressants’ sexual side effects can often be managed—while preserving the antidepressant effect—by altering dosages, switching to another drug class, or adding an “antidote.” Understanding the benefits and risks of each strategy can help you:

  • base treatment choices on your patient’s history and side-effect experience
  • improve long-term compliance with antidepressant regimens.


Antidepressants may affect one or more phases of sexual functioning:

  • desire (libido)
  • arousal (erection or vaginal lubrication)
  • orgasm/ejaculation.

Sexual symptoms linked to antidepressants range from diminished interest/arousal and delayed orgasm to heightened sexual functioning (Table 1). Resulting sexual dysfunction can impair quality of life and intimate relationships and discourage patients from taking antidepressants (Box) 1,2

Table 1

Sexual side effects linked to antidepressants

Most common effectsShown by these drugs
Decreased desireTCAs, MAOIs, SSRIs
Delayed or absent ejaculation/orgasmTCAs, MAOIs, SSRIs
Impaired erectionTCAs, MAOIs, SSRIs
Less common effects
Increased desireBupropion
Spontaneous/prolonged erectionsSSRIs, CMI,bupropion, trazodone, nefazodone
Premature/retrograde/painful ejaculationsTCAs, trazodone, nefazodone
PriapismSSRIs, CMI, bupropion, trazodone, nefazodone
Spontaneous orgasms (associated with yawning)SSRIs, CMI, bupropion
Altered sexual sensation and sensitivitySSRIs, CMI, bupropion
TCAs: tricyclics
MAOIs: monoamine oxidase inhibitors
SSRIs: selective serotonin reuptake inhibitors
CMI: clomipramine

Although most reports have focused on SSRIs, all antidepressant classes have been associated with sexual dysfunction, with prevalence likely influenced by differences in neurotransmitter modulation (Table 2).1,3,4 The highest rates of sexual side effects have been reported with SSRIs, certain tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs).

A recent study reported similarly high rates with mirtazapine, but its small sample size limits conclusions about side effect prevalence with this drug.1 Other studies have found significantly lower rates with bupropion and nefazodone.

TCAs’ sexual side-effect rates and types depend on how much each drug inhibits serotonin reuptake. Clomipramine appears to have the highest rates of sexual dysfunction—particularly anorgasmia—probably because it inhibits the serotonin transporter more than do other TCAs.5 In TCAs with lesser effects on serotonergic neurotransmission, alpha-adrenergic and cholinergic receptor blockade may cause sexual side effects—particularly erectile dysfunction (ED).

Cholinergic agonists such as bethanechol, 10 to 50 mg/d, may reverse sexual dysfunction caused by anticholinergic effects.6 Cyproheptadine—a nonselective serotonin receptor antagonist—has also shown benefit at 4 to 12 mg/d in treating TCA-related sexual side effects.7

MAOIs. Sexual side effects appear to be more prevalent with MAOIs than with TCAs,4 perhaps similar to the rate seen with SSRIs. MAOIs directly increase serotonergic neurotransmission, and their substantial alpha-adrenergic antagonist effects may also produce sexual side effects.

Waiting for symptoms to subside may be appropriate, as anorgasmia caused by MAOIs may remit spontaneously. Sildenafil8 and cyproheptadine9 may reverse MAOI sexual side effects, although serious toxicity has been reported in a patient taking cyproheptadine and an MAOI.10

SSRIs. Increased serotonergic neurotransmission is widely believed to cause SSRI sexual side effects. Resulting secondary effects—such as inhibited central dopamine release, increased prolactin secretion, and inhibited nitric oxide synthesis—may also play important roles.

In general, SSRIs appear to alter sexual functioning in 40% to 60% of patients—both men and women. Anorgasmia is the most commonly reported sexual symptom.

Although all SSRIs are associated with sexual dysfunction, some studies have found higher rates with paroxetine. One study associated paroxetine with significantly higher rates of ED compared with other SSRIs. The authors attributed this finding to paroxetine’s greater anticholinergic effects or to its directly decreasing nitric oxide synthesis.3


Waiting. The simplest, safest way to manage SSRI-related sexual dysfunction is to wait and see if side effects resolve spontaneously. Sexual side effects improve without treatment in approximately 20% of cases,3 although improvement is often incomplete. Moreover, several months may pass before symptoms diminish adequately, making this strategy impractical for patients with substantial sexual dysfunction.

Dosing changes. Because SSRIs’ sexual side effects appear to be dose-related,11 carefully reducing the dosage may reduce sexual dysfunction without compromising antidepressant efficacy. This strategy is most likely to sustain remission when you avoid dosages that have proven ineffective. For example, consider a patient who achieves remission of depressive symptoms when fluoxetine is increased from 20 to 40 mg/d. If sexual side effects emerge at 40 mg/d, relapse may be less likely at 30 mg/d than at 20 mg/d.


Talking to patients about sexual function

Sexual side effects are common in patients taking selective serotonin reuptake inhibitors.1 Sexual side effects diminish patients’ quality of life and significantly decrease adherence to antidepressant regimens,2 which in turn diminishes depression treatment efficacy.

Hidden problem. Drug-related sexual side effects often go undetected because:

  • patients are too embarrassed to discuss sexual problems with their physicians
  • onset is often later and more insidious than that of other antidepressant side effects
  • they may be difficult to distinguish from pre-existing sexual dysfunction caused by depression, other medical reasons, or psychosocial factors
  • physicians often fail to educate patients about them.

Clinical tips. These problems point out the importance of obtaining a sexual history before starting antidepressant therapy, educating patients about the potential for sexual side effects with antidepressants (including when they occur and what may be done to manage them), and directly asking patients about specific sexual side effects at follow-up visits.


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