Curbside Consults

VOL 116 / NO 6 / DECEMBER 2004 / POSTGRADUATE MEDICINE

Is antidepressant plus sildenafil a recipe for priapism?

Q: Are drugs such as trazodone hydrochloride (Desyrel), which has a side effect potential for priapism, contraindicated in patients taking erectile dysfunction (ED) drugs, such as sildenafil citrate (Viagra)?

Internist, Arizona

A: ED is defined as the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance (1). As many as 30 million men in the United States may be affected by ED. Prevalence is higher in men who have depression or other medical conditions, including diabetes, heart disease, and hypertension. Certain medications also may increase the risk of ED.

Priapism is a painful erection that lasts longer than 6 hours and occurs when blood becomes trapped in the penis. Priapism is rare, but it can result in scarring, permanent damage to tissues, and loss of erectile function. Consequently, men who experience an erection that lasts longer than 4 hours should contact their physician immediately. Priapism has been reported infrequently in men who use a wide range of treatment options for ED.

Sildenafil is one of several recently developed oral agents for treatment of ED. It selectively inhibits phosphodiesterase type 5 and enhances the effect of endogenous nitric oxide. This in turn produces penile smooth-muscle relaxation, arterial dilation, and inflow of blood, which leads to penile enlargement.

In a meta-analysis of 27 trials involving 6,659 men (2), sildenafil was more likely than placebo to lead to successful sexual intercourse (57% versus 21%) and resulted in a greater percentage of men experiencing at least one session of intercourse during treatment (83% versus 45%). Treatment was effective in men with ED from a wide range of origins, including depression and other psychologic factors. Treatment effectiveness varied little by dose (25 to 100 mg). However, adverse effects--particularly headache, flushing, dyspepsia, and abnormal vision--increased considerably at higher doses. Use of sildenafil has only rarely been associated with priapism (3).

Trazodone is an oral antidepressant that has anxiolytic, sedative, and hypnotic effects and also has been reported to increase libido and sexual function. In a systematic review and meta-analysis of six trials involving 396 men (4), trazodone was more likely than placebo to lead to a "positive treatment response" (37% versus 20%), although this difference was not statistically significant. Subgroup analyses suggested that, compared with men who had mixed or physiologic ED, men who had psychogenic ED were more likely to have a positive treatment response with trazodone than with placebo (63% versus 23%). The efficacy of trazodone was greater at higher daily doses (150 to 200 mg versus 50). Adverse events included dry mouth (19%), sedation (16%), dizziness (16%), and fatigue (15%). Priapism was reported in only one patient in a trazodone treatment group. However, priapism has been associated with trazodone use in other settings.

A May 2004 MicroMedEx computer search revealed that neither sildenafil nor other currently available phosphodiesterase type 5 inhibitors are listed as having known interactions with trazodone or as being contraindicated in men taking trazodone. However, men taking trazodone were excluded from randomized trials that evaluated sildenafil. Priapism or prolonged erections were reported infrequently with sildenafil during postmarketing surveillance. Nearly half of the men who reported priapism or prolonged erections had used sildenafil in combination with other drug therapy for ED (eg, alprostadil, trazodone) (5).

These results suggest that the absolute risk of priapism may be slightly higher in men using sildenafil in combination with other ED therapies, but there is no known contraindication to their combined use. Selective serotonin reuptake inhibitors used as antidepressant medications have not been associated with priapism.

Timothy J. Wilt, MD, MPH
Professor of Medicine
University of Minnesota Medical School--Twin Cities
Staff Physician, Minneapolis VA Center for Chronic Disease Outcomes Research

Howard A. Fink, MD, MPH
Assistant Professor of Medicine
University of Minnesota Medical School--Twin Cities
Staff Physician, Minneapolis VA Center for Chronic Disease Outcomes Research and the Geriatrics Research and Education Clinical Center

References

1. NIH Consensus Conference: impotence. NIH Consensus Development Panel on Impotence. JAMA 1993;270(1):83-90
2. Fink HA, MacDonald R, Rutks IR, et al. Sildenafil for male erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med 2002;162(12):1349-60
3. Sur RL, Kane CJ. Sildenafil citrate-associated priapism. Urology 2000;55(6):950
4. Fink HA, MacDonald R, Rutks IR, et al. Trazodone for male erectile dysfunction: a systematic review and meta-analysis. BJU Int 2003;92(4):441-6
5. McEvoy GK, ed. AHFS Drug Information 2002. Bethesda: American Society of Health-System Pharmacists, 2002;1905-16

Are inhaled corticosteroids safe in pregnancy?

Q: I have a patient with chronic upper respiratory allergies who has done well with daily use of a nasal corticosteroid spray. She has recently become pregnant, and her obstetrician insists that she stop using the nasal spray because it is considered a safety category C drug (ie, animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans). Are inhaled corticosteroids really a potential danger during pregnancy?

Primary care physician, Texas

A: Safety data on the use of most inhaled corticosteroids in pregnancy are lacking. However, results from a study of the use of an inhaled corticosteroid during pregnancy (1) suggest that at least one drug in this category--budesonide--does not present a danger to mother or child. Using data derived from the Swedish Medical Birth Register (which includes 99% of births in Sweden), Norjavaara and de Verdier (1) compared pregnancy outcomes for mothers who used the inhaled corticosteroid budesonide with outcomes for mothers who reported no usage. Among the 293,948 births identified from 1995 to 1998, the investigators found that the 2,968 mothers who had used budesonide during early pregnancy gave birth to infants of normal gestational age, birth weight, and length; the rates of stillbirths and multiple births were not increased.

Because of the Swedish data, the US Food and Drug Administration has assigned both inhaled and intranasal budesonide a safety category B rating. This rating designates that (1) animal studies have not shown a risk to the fetus, but there are no adequate studies in pregnant women or (2) animal studies have shown an adverse effect, but adequate studies in pregnant women have not shown a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk later in pregnancy. All other inhaled corticosteroids are category C drugs.

Newer inhaled corticosteroids, such as fluticasone propionate, are more potent per microgram than older agents but appear to have less bioavailability. No adequate, well-controlled studies of fluticasone in pregnancy have been performed. Because of the lack of safety data on this drug and the other newer agents, the American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma, and Immunology (2) state, "it would not be unreasonable to continue a different (from beclomethasone [dipropionate] or budesonide) inhaled corticosteroid in a patient well-controlled by that drug (fluticasone or other newer agents) prior to pregnancy."

Michael S. Blaiss, MD
Clinical Professor of Pediatrics and Medicine, University of Tennessee, Health Science Center, College of Medicine, Memphis

References

1. Norjavaara E, de Verdier MG. Normal pregnancy outcomes in a population-based study including 2,968 pregnant women exposed to budesonide. J Allergy Clin Immunol 2003;111(4):736-42
2. The use of newer asthma and allergy medications during pregnancy. The American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma, and Immunology (ACAAI). Ann Allergy Asthma Immunol 2000;84(5):475-80

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