Evidence-Based Reviews

Prescribing to preserve or restore sexual function

Current Psychiatry. 2004 March;3(3):57-76

References

1. National Institutes of Health consensus conference on impotence. JAMA 1993;270:83-90.

2. Montejo-Gonzalez AL, Llorca G, Izquierdo JA, et al. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 1997;23:176-94.

3. Harrison WM, Rabkin JG, Ehrhardt AA, et al. Effects of antidepressant medication on sexual function: a controlled study. J Clin Psychopharmacol 1986;6:144-9.

4. Benazzi F, Mazzoli M. Fluoxetine-induced sexual dysfunction: a dose-dependent effect? Pharmacopsychiatry 1994;27:246.-

5. Clinical management of depression: bupropion—an update. Monograph series, vol.1, no. 1. Proceedings of a closed symposium: Antidepressant drug therapy: bupropion—an update meeting, Boca Raton, FL, October 30-31, 1992.

6. Rothschild AJ. Selective serotonin reuptake inhibitor-induced sexual dysfunction: efficacy of a drug holiday. Am J Psychiatry 1995;152:1514-16.

7. Rosen RC, Lane RM, Menza M. Effects of SSRIs on sexual function: a critical review. J Clin Psychopharmacol 1999;19:67-85.

8. Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J Clin Psychopharmacol 1998;18:274-81.

9. Koutouvidis N, Pratikakis M, Fotiadou A. The use of mirtazapine in a group of 11 patients following poor compliance to selective serotonin reuptake inhibitor treatment due to sexual dysfunction. Int Clin Psychopharmacol 1999;14:253-5.

10. Gelenberg AJ, McGahuey C, Laukes C, et al. Mirtazapine substitution in SSRI-induced sexual dysfunction. J Clin Psychiatry 2000;61:356-60.

11. Segraves RT, Kavoussi R, Hughes AR, et al. Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment. J Clin Psychopharmacol 2000;20:122-8.

12. Masand PS, Ashton AK, Gupta S, Frank B. Sustained-release bupropion for selective serotonin reuptake inhibitor-induced sexual dysfunction: a randomized, double-blind, placebo-controlled, parallel-group study. Am J Psychiatry 2001;158:805-7.

13. Farah A. Relief of SSRI-induced sexual dysfunction with mirtazapine treatment. J Clin Psychiatry 1999;60:260-1.

14. Smith SM, O’Keane V, Murray R. Sexual dysfunction in patients taking conventional antipsychotic medication. Br J Psychiatry 2002;181:49-55.

15. Kotin J, Wilbert DE, Verburg D, Soldinger SM. Thioridazine and sexual dysfunction. Am J Psychiatry 1976;133:82-5.

16. Guthrie SK. Clinical issues associated with maintenance treatment of patients with schizophrenia. Am J Health-Syst Pharm 2002;59(suppl 5):519-24.

17. Goodnick PJ, Rodriguez L, Santana O. Antipsychotics: impact on prolactin levels. Expert Opin Pharmacother 2002;3:1381-91.

18. Brunet M, Rodamilans M, Martinez-Osaba MJ, et al. Effects of long-term antiepileptic therapy on the catabolism of testosterone. Pharmacol Toxicol 1995;76:371-5.

19. Heroz AG, Levesque LA, Drislane FW, et al. Phenytoin-induced elevation of serum estradiol and reproductive dysfunction in men with epilepsy. Epilepsia 1991;32:550-3.

20. Husain AM, Carwile ST, Miller PP, Radtke RA. Improved sexual function in three men taking lamotrigine for epilepsy. South Med J 2000;93:335-6.

21. Nurnberg HG, Hensley PL, Gelenberg AJ, et al. Treatment of antidepressant-associated sexual dysfunction with sildenafil. A randomized controlled trial. JAMA 2003;289:56-64.

22. Nurnberg HG, Gelenberg A, Hargreave TB, et al. Efficacy of sildenafil citrate for the treatment of erectile dysfunction in men taking serotonin reuptake inhibitors. Am J Psychiatry 2001;158:1926-8.

23. Shrivastava RK, Shrivastava S, Overweg N, Schmitt M. Amantadine in the treatment of sexual dysfunction associated with selective serotonin reuptake inhibitors. J Clin Psychopharmacol 1995;15:83-4.

24. Worthington JJ, 3rd, Simon NM, Korbly NB, et al. Ropinirole for antidepressant-induced sexual dysfunction. Int Clin Psychopharmacol 2002;17:307-10.

25. Gross MD. Reversal by bethanechol of sexual dysfunction caused by anticholinergic antidepressants. Am J Psychiatry 1982;139:1193-4.

26. Yager J. Bethanechol chloride can reverse erectile and ejaculatory dysfunction induced by tricyclic antidepressants and mazindol: case report. J Clin Psychiatry 1986;47:210-11.

Phosphodiesterase (PDE-5) inhibitors have become widely used as first-line oral medications for ED secondary to numerous causes. Sildenafil has demonstrated effectiveness in treating SSRI-induced ED compared with placebo. Tadalafil and vardenafil have not been studied in patients taking SSRIs.

Table 4

Side effects, drug interactions associated with other ED agents

Drug	Adverse effects	Drug interactions
Amantadine	Aggression, altered mentation, anxiety, heart failure (rare), insomnia, leukopenia (rare), nausea Livedo reticularis (with extended use), neuroleptic malignant syndrome (upon discontinuation), orthostatic hypotension, psychoses	Bupropion (increased adverse events) Triamterene (may increase amantadine plasma concentration)
Bethanechol	Cholinergic effects (increased GI motility, lacrimation, miosis, urinary frequency) Diaphoresis, flushing, headache, hypotension, tachycardia	Anticholinergics (decreased effects of both agents) Cholinesterase inhibitors (increased cholinergic effects), Ganglionic blockers (severe hypotension)
Bupropion	Agitation, amblyopia, arrhythmias (rare), constipation, diaphoresis, dizziness, extrapyramidal symptoms (rare), headache, hypertension Hypoprolactinemia, insomnia, leukopenia (minor), nausea/vomiting Alcohol psychoses (rare), seizures, serum sickness (rare), taste perversion, tinnitus, tremor, urinary frequency Urticaria, weight gain (rare), weight loss, xerostomia	CYP-2D6 inducers and inhibitors (altered bupropion plasma concentration) Dopamine-receptor agonists (increased adverse effects) MAOIs (increased seizures and psychoses) QT-prolonging agents (increased QT-prolongation) Alcohol, systemic steroids, theophylline (increased seizures)
Mirtazapine	Somnolence, constipation, xerostomia, increased appetite, weight gain, dizziness, abnormal dreams, confusion Hyperlipidemia, flu-like symptoms, back pain	MAO inhibitors, linezolid, CNS depressants (increased sedative effects) Alcohol (may increase CNS depression) St John’s wort (may decrease mirtazapine levels)
Ropinirole	Abdominal pain, anxiety, arthralgias, confusion, constipation, diaphoresis, dyskinesias, dyspepsia, headache Hallucinations, insomnia, nausea/vomiting, orthostatic hypotension, peripheral edema Somnolence, tremor, upper respiratory infection, urinary tract infection, visual disturbances, xerostomia	CYP-1A2 inducers and inhibitors (altered ropinirole plasma concentration) Dopamine-receptor antagonists (decreased efficacy of both agents)

In one 6-week study,²¹ 54.4% of patients taking both an SSRI and sildenafil, up to 100 mg, showed significantly improved erectile function, arousal, ejaculation, orgasm, and overall satisfaction. In another study,²² SSRI-treated patients receiving sildenafil, 5 to 200 mg before sexual activity, reported noticeably improved ability to achieve and maintain erection, ejaculate, and achieve orgasm.

Sildenafil should not be taken concomitantly with agents or products containing nitrates. Use sildenafil with caution in patients with a blood pressure >170/110 mm Hg or <90/50 mm Hg, unstable angina, or retinitis pigmentosa. Also use sildenafil cautiously in patients who have suffered myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.

Bupropion. In double-blind trials,^11,12 the agent’s sustained-release form has shown effectiveness as an alternative or adjunct to SSRIs in treating SSRI-induced ED. Prescribe at 150 mg nightly when used as an adjunct.

Bupropion is contraindicated in patients with bulimia, anorexia nervosa, and seizure disorders, and in patients taking MAOIs. Use bupropion cautiously in patients with cranial trauma, renal or hepatic insufficiency, uncontrolled hypertension, myocardial infarction, unstable cardiovascular disease, psychosis, and bipolar disorder, and in patients abusing alcohol or taking warfarin.

Amantadine, an oral dopamine-receptor agonist with innate cholinergic effects, has shown effectiveness against SSRI-induced ED when given at 200 mg bid in a small trial.²³

Avoid using amantadine in patients with closed-angle glaucoma, and use with caution in patients with heart failure and in persons age 65 and older.

Mirtazapine, 15 mg/d, has shown effectiveness as an SSRI alternative and as SSRI augmentation therapy to alleviate sexual dysfunction.^12,13

Mirtazapine is contraindicated in patients with hypersensitivity or in patients who have used an MAOI within 14 days. Be careful when combining mirtazapine with an SSRI as the combination may increase the risk of serotonin syndrome.

Ropinirole, an oral dopamine 2-receptor agonist used to treat Parkinson’s disease, has shown effectiveness against antidepressant-induced ED when given at 0.25 mg/d and titrated across 4 weeks to 2 to 4 mg/d.²⁴ Use ropinirole carefully in patients with bradycardia, dyskinesias, hallucinations, renal or hepatic insufficiency, and hypotension.

Bethanechol, an oral cholinergic agent used to treat urinary retention, has been described in case reports to alleviate TCA-induced ED when given at 20 mg 1 to 2 hours before sexual activity.^25,26 Bethanechol is contraindicated in patients with hyperthyroidism, peptic ulcer disease, asthma, bradycardia, hypotension, coronary artery disease, epilepsy, Parkinson’s disease, urinary bladder neck obstruction, spastic GI disturbances, acute inflammatory GI lesions, peritonitis, and vagotonia.

Related resources

Miller TA. Diagnostic evaluation of erectile dysfunction. Am Fam Physician 2000;61:95-110.
Viera AJ, Clenney TL, Shenenberger DW, Green GF. Newer pharmacologic alternatives for erectile dysfunction. Am Fam Physician 1999;60:1159-72.
British Medical Journal Web site search: erectile dysfunction. http://bmj.bmjjournals.com/cgi/collection/erectile_dysfunction

Drug brand names

Amantadine • Symmetrel
Aripiprazole • Abilify
Bethanechol • Urecholine
Bupropion • Wellbutrin
Buspirone • BuSpar
Carbamazepine • Tegretol
Dihydrocodeine • Synalgos
Disulfiram • Antabuse
Gabapentin • Neurontin
Lamotrigine • Lamictal
Linezolid • Zyvox
Lisinopril • Prinivil, others
Lithium • Eskalith, others
Metformin • Glucophage
Mirtazapine • Remeron
Nefazodone • Serzone
Oxcarbazepine • Trileptal
Paroxetine • Paxil
Phenytoin • Dilantin
Risperidone • Risperdal
Ropinirole • Requip
Sertraline • Zoloft
Sildenafil • Viagra
Simvastatin • Zocor
Tadalafil • Cialis
Triamterene • Dyazide, others
Trazodone • Desyrel, others
Vardenafil • Levitra
Warfarin • Coumadin