Evidence-Based Reviews

Restoring sexual function: Which medications show benefit?

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When trying centrally acting or topical agents, also address patients’ psychopathologies.



Sexual disorders such as premature ejaculation, erectile dysfunction (ED), and low libido reduce quality of life in patients with depression, anxiety, and other psychiatric illnesses. In addition, sexual dysfunction is a side effect of many drugs used to treat psychiatric disorders.1

Psychiatry—with its biopsychosocial model—can easily assume the evaluation and treatment of sexual disorders. To inform your practice, this article provides an update on pharmacotherapy for the 3 most common sexual disorders. Its emphasis on biologic treatment is not intended to minimize the importance of psychological interventions.

Premature ejaculation

Premature ejaculation is one of the most common male sexual complaints. In some surveys, approximately 30% of men express concern about ejaculating too rapidly.2 Behavioral therapy often is effective (Box 1), but in my experience most male patients prefer a pharmacologic approach to sexual problems.

Anesthetic creams. Locally applied anesthetic creams—such as prilocaine, lidocaine mixtures, and creams consisting of natural herbs—can increase ejaculatory latency by approximately 7 to 10 minutes. The major side effect of these preparations is penile hypoanesthesia. The man also must use a condom or wash off the cream before vaginal penetration to minimize vaginal absorption.3

Box 1

Start-stop technique for premature ejaculation*
  1. With male lying on back, partner strokes penis until male signals that ejaculation will occur with continued stimulation
  2. Stroking stops, and erection is allowed to subside, then stroking resumes
  3. Repeat steps 1 and 2 four times, 2 times/week
  4. Ejaculatory latency will increase
  5. Partner assumes female-superior position and moves up and down until male indicates ejaculation is imminent

* Behavioral therapy for heterosexual couples. Oral-genital stimulation can be utilized between steps 4 and 5

† Frenulum squeeze technique is similar except that partner squeezes frenulum of penis at sign of male excitement

Centrally active medications. No medications are FDA-approved for premature ejaculation, but case reports describe the off-label use of monoamine oxidase inhibitors, tricyclic antidepressants, and antipsychotics.4 The selective serotonin reuptake inhibitors (SSRIs) paroxetine, sertraline, and fluoxetine also delay ejaculation, as shown in double-blind controlled studies.

Among the SSRIs, paroxetine appears to have the greatest effect on ejaculatory latency (Table 1).5 Most trials have found that the dose needed to delay ejaculation is similar to the dose necessary to treat depressive disorders.

Clomipramine, a tricyclic antidepressant with strong serotonergic activity, has been shown in double-blind trials to be effective in treating rapid ejaculation on an as-needed basis. By contrast, SSRIs appear to require chronic dosing to be effective. Clomipramine usually is taken 4 to 6 hours before coitus in doses of 25 to 50 mg. Low-dose lorazepam (0.5 to 1 mg) taken 30 minutes before coitus also may be effective in some men.2

Some case reports suggest that phosphodiesterase type 5 inhibitors (PDE-5 inhibitors) may help to delay ejaculation, but this effect has not been borne out in double-blind studies.6

Table 1

Drug treatment options for premature ejaculation

DrugDosageCommon side effects
Paroxetine20 to 40 mg/dNausea, headache
Clomipramine25 to 50 mg 4 to 6 hours before sexual activityNausea, fatigue
Lorazepam0.5 to 1 mg 30 minutes before sexual activitySedation
Source: Reference 5
Recommendation. Most psychiatrists can easily provide pharmacotherapy for premature ejaculation because we commonly use the medications in clinical practice. As initial treatment, I recommend trying clomipramine, 25 to 50 mg 4 to 6 hours before coitus. Other authors prefer a trial of paroxetine, 20 mg daily.

Erectile dysfunction

Men with major depressive disorder, anxiety disorders, and psychotic disorders have higher rates of ED, compared with the general male population. ED also can be a side effect of—and adversely affect adherence to—antidepressant and antipsychotic therapy.7 Restored erectile function can positively affect patients’ self-esteem and sense of personal efficacy and may facilitate recovery from depression.8

PDE-5 inhibitors. Nitric oxide release triggers the production of cyclic guanosine monophosphate, which leads to decreased intracellular calcium, smooth muscle relaxation, and penile erection. All available PDE-5 inhibitors work by inhibiting the degradation of cyclic guanosine monophosphate. They are highly specific, vary somewhat in selectivity for other phosphodiesterase enzyme types, and differ in duration of action (Table 2).

Common side effects include dyspepsia, stuffy nose, and headache. The use of PDE-5 inhibitors with nitrates is contraindicated because of the risk of severe hypotension. Use PDE-5 inhibitors cautiously:

  • with alpha blockers because of the risk of hypotension
  • in men with aortic stenosis, recent myocardial infarction, unstable angina, heart failure, arrhythmias, degenerative retinal disease, or poorly controlled hypertension.9
Also warn patients about the rare possibility of priapism and to go immediately to the nearest emergency room if an erection lasts >4 hours without sexual stimulation.


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