Table 3
Phosphodiesterase type 5 inhibitors: A comparison
| Medication | Dose rangea | Pharmacokinetics | Side effects | Significant drug interactions |
|---|---|---|---|---|
| Avanafil | 50 to 200 mg, 30 minutes before sexual activity | Bioavailability: N/A (high-fat meal delays Tmax by 60 minutes and reduces Cmax by 24% to 39%; clinically insignificant) Half life: 5 hours Metabolism: CYP3A4 | Headache, flushing, nasal congestion, nasopharyngitis, backache | Strong CYP3A4 inhibitors (increased avanafil levels) Contraindicated within 12 hours of nitrate use (eg, nitroglycerin) |
| Sildenafil | 25 to 100 mg, 1 to 2 hours before sexual activity | Bioavailability: 41% (food/high-fat meal delays Tmax by 60 minutes and reduces Cmax by 29%) Half life: 4 hours Metabolism: CYP3A4 | Headache, flushing, erythema, indigestion, insomnia, visual disturbances (blue vision) | Strong CYP3A4 inhibitors (increased sildenafil levels) Contraindicated within 24 hours of nitrate use |
| Tadalafil | 10 to 20 mg, 30 minutes before sexual activity | Bioavailability: N/A (not affected by food) Half life: 17.5 hours (duration of action up to 36 hours) Metabolism: CYP3A4 | Headache, flushing, indigestion, nasal congestion, dizziness, myalgia, and back pain | Strong CYP3A4 inhibitors (increased tadalafil levels) Contraindicated within 48 hours of nitrate use |
| Vardenafil | 5 to 20 mg, 30 minutes to 2 hours before sexual activity | Bioavailability: 15% for film-coated tablet (high-fat meal reduces Cmax by 18% to 50%) Half life: 4 to 5 hours Metabolism: CYP3A4 | Headache, flushing, indigestion, nasal congestion, dizziness, visual disturbances (blue vision) | Strong CYP3A4 inhibitors (increased vardenafil levels) Contraindicated within 24 hours of nitrate use |
| aTypical dose range for treatment of erectile dysfunction Cmax: maximum concentration; CYP: cytochrome P450; Tmax: time to maximum concentration Source: Micromedex® Healthcare Series [Internet database]. Greenwood Village, CO: Thomson Healthcare. Accessed October 10, 2012 | ||||
Limited evidence for sildenafil
Case reports, a few small open-label trials, and 1 prospective, randomized controlled trial (RCT) have evaluated sildenafil as an adjunctive treatment for serotonergic antidepressant-associated sexual dysfunction in women.6,9 Nurnberg et al6 examined the efficacy of adjunctive sildenafil in women with SSRI-induced sexual dysfunction. This 8-week, placebo-controlled, double-blind, RCT used a flexible dose (50 or 100 mg), intention-to-treat design to assess the effect of sildenafil on 98 premenopausal women whose depression was in remission. Ten patients were taking the serotonin-norepinephrine inhibitor venlafaxine, 1 was taking the TCA clomipramine, and 87 were receiving an SSRI. Patients were instructed to take sildenafil or placebo 1 to 2 hours before sexual activity. The primary outcome was mean change from baseline on the Clinical Global Impression-Sexual Function (CGI-SF) scale.
Women taking sildenafil showed significant improvement compared with those taking placebo, with a treatment difference between groups of 0.8 (95% CI, 0.6 to 1.0; =.001). Additionally, 23% of sildenafil-treated patients reported no improvement with the intervention, compared with 73% of patients receiving placebo. Secondary outcomes using 3 validated scales that evaluated specific phases of sexual function found that patients’ orgasmic function significantly benefited from sildenafil treatment, while desire, arousal, and overall satisfaction were not significantly different.
Although these findings seem to support sildenafil for treating serotonergic antidepressant-associated sexual dysfunction in women, the study had a relatively small treatment effect in a well-defined patient population; therefore, replication in future trials and different patient populations is warranted. Overall, sildenafil was well tolerated, despite patient reports of headaches, flushing, visual disturbances, dyspepsia, nasal congestion, and palpitations. Finally, cost vs benefit should be considered; PDE5 inhibitors may not be covered by insurance or may require prior authorization.
CASE CONTINUED: Symptoms resolve
Bupropion is not an appropriate choice for Mrs. L because of her seizure risk. Mirtazapine is ruled out because in the past she experienced excessive somnolence that impaired her ability to function. You are not comfortable prescribing nefazodone because of its risk of hepatotoxicity or suggesting that Mrs. L take a “drug holiday” (stop taking any antidepressants for a short period) because of the risk of depressive relapse. You suggest that Mrs. L continue to take sertraline because sometimes antidepressant-induced sexual dysfunction resolves after ≥6 months of treatment with the same agent, but she is adamant that her relationship with her husband will deteriorate if she waits that long. She also declines cognitive-behavioral therapy because her job doesn’t allow the time or flexibility to commit to the sessions.
You prescribe sildenafil, 50 mg, and instruct Mrs. L to take 1 tablet 1 to 2 hours before sexual activity. This treatment improves her ability to achieve orgasm. She tolerates the drug well and after 8 weeks of treatment her CGI-SF score improves from 6 at baseline, indicating extreme dysfunction, to 2, indicating normal function. Ten months into her sertraline treatment, Mrs. L discovers she no longer requires sildenafil to achieve orgasm.