Evidence-Based Reviews

Restoring sexual function: Which medications show benefit?

Current Psychiatry. 2008 June;7(6):19-36

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

References

1. Segraves RT. Female sexual disorders: psychiatric aspects. Can J Psychiatry 2002;47:419-25.

2. Segraves RT. Rapid ejaculation: a review of nosology, prevalence and treatment. Int J Impot Res 2006;18(suppl 1):S24-S32.

3. Riley A, Segraves RT. Treatment of premature ejaculation. Int J Clin Pract 2006;60(6):694-7.

4. Duterte E, Segraves R, Althof S. Psychotherapy and pharmacotherapy of sexual dysfunctions. In: Nathan P, Gorman J, eds. A guide to treatments that work. New York, NY: Oxford University Press; 2007:531-60.

5. Waldinger M. Male ejaculation and orgasmic disorders. In: Balon R, Segraves RT, eds. Handbook of sexual dysfunction. Boca Raton, FL: Taylor & Francis; 2005:215-48.

6. McMahon C, Stuckey B, Andersen M, et al. Efficacy of sildenafil citrate (Viagra) in men with premature ejaculation. J Sex Med 2005;2:368-75.

7. Segraves R. Treatment of erectile dysfunction: a psychiatric perspective. Primary Psychiatry 2004;11(12):35-45.

8. Hartmann U. Depression and sexual dysfunction. J Men’s Health Gender 2007;4:18-25.

9. Shabsigh R, Seftel A, Rosen R, et al. Review of time of onset and duration of clinical efficacy of phosphodiesterase inhibitors in treatment of erectile dysfunction. Urology 2006;68:689-96.

10. Mukherjee B, Shivakumar T. A case of sensorineural deafness following ingestion of sildenafil. J Laryngol Otol 2007;121(4):395-7.

11. Pomeranz HD, Bhavsar AR. Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (Viagra): a report of seven new cases. J Neuroophthalmol 2005;25(1):9-13.

12. Padma-Nathan H, Christ G, Adaikan G, et al. Pharmacotherapy for erectile dysfunction. In: Lue T, Basson R, Rosen R, et al, eds. Sexual medicine: sexual dysfunctions in men and women. Paris, France: Health Publications; 2004:505-68.

13. Safarinejad M. Salvage of sildenafil failures with cabergoline: a randomized, double-blind, placebo-controlled study. Int J Impot Res 2006;18:550-8.

14. Nickel M, Moleda D, Loew T, et al. Cabergoline treatment in men with psychogenic erectile dysfunction: a randomized placebo-controlled study. Int J Impot Res 2007;19:164-7.

15. Montorsi F, Althof S. Partner responses to sildenafil citrate (Viagra) treatment of erectile dysfunction. Urology 2004;63:762-7.

16. Wise T. Psychosocial effects of sildenafil therapy for erectile dysfunction. J Sex Marital Ther 1999;25(2):145-50.

17. Pallas J, Levine SB, Althof SE, Risen CB. A study using Viagra in a mental health practice. J Sex Marital Ther 2000;26:41-50.

18. Basson R, McInnes R, Smith MD, et al. Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder. J Womens Health Gend Based Med 2002;11:367-77.

19. Berman JR, Berman LA, Toler SM, et al. Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: a double-blind, placebo controlled study. J Urol 2003;170(6 Pt 1):2333-8.

20. Caruso S, Intelisano G, Lupo L, Agnello C. Premenopausal women affected by sexual arousal disorder treated with sildenafil: a double-blind, cross-over, placebo-controlled study. BJOG 2001;108:623-8.

21. Sherwin BB, Gelfand MM. The role of androgen in the maintenance of sexual functioning in oophorectomized women. Psychosom Med 1987;49:397-409.

22. Shifren JL, Braunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med 2000;343:682-8.

23. Segraves RT, Woodard T. Female hypoactive sexual desire disorder: history and current status. J Sex Med 2006;3:408-18.

24. Basaria S, Dobs AS. Clinical review: controversies regarding transdermal androgen therapy in postmenopausal women. J Clin Endocrin Metab 2006;91:4743-52.

25. Segraves RT, Clayton A, Croft H, et al. Bupropion for the treatment of hypoactive sexual desire disorder in premenopausal women. J Clin Psychopharamacol 2004;24:339-42.

26. Pfaus J, Giuliano F, Gelez H. Bremelanotide: an overview of preclinical CNS effects on female sexual function. J Sex Med 2007;4(suppl 4):269-79.

27. Ito T, Polan M, Whipple B, Trant A. The enhancement of female sexual function with ArginMax, a nutritional supplement, among women suffering in menopausal status. J Sex Marit Ther 2006;32:359-78.

28. Ferguson DM, Steidle CP, Singh GS, et al. Randomized, placebo-controlled, double blind, crossover design trial of the efficacy and safety of Zestra for Women in women with and without female sexual arousal disorder. J Sex Marital Ther 2003;29(suppl 1):33-44.

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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*

With male lying on back, partner strokes penis until male signals that ejaculation will occur with continued stimulation^†
Stroking stops, and erection is allowed to subside, then stroking resumes
Repeat steps 1 and 2 four times, 2 times/week
Ejaculatory latency will increase
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.

Clinical Point

The SSRI dose needed to delay ejaculation usually is similar to the dose needed 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

Drug	Dosage	Common side effects
Paroxetine	20 to 40 mg/d	Nausea, headache
Clomipramine	25 to 50 mg 4 to 6 hours before sexual activity	Nausea, fatigue
Lorazepam	0.5 to 1 mg 30 minutes before sexual activity	Sedation
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.