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This Month's Question

Response by Robert T. Segraves, MD, PhD, Posted 09/04/07

Depression is a common disease affecting millions of Americans. The lifetime prevalence of major depressive disorder in the adult population in the United States is estimated to be 32.6 to 35.1 million.¹ Antidepressants are the most commonly prescribed drugs in the United States²; however, adverse sexual side effects cause some patients to discontinue treatment, resulting in relapse.³ Published reports indicate that up to 50% of patients receiving antidepressant therapy experience sexual side effects.⁴ Among the common, yet unrecognized, sexual side effects cited as a reason for discontinuing therapy is ED.^5,6

Clinicians have several options to reduce this dropout rate. One option is to wait for the patient to develop a tolerance for the antidepressant medication, as symptoms may resolve in some cases.⁵ If that fails, clinicians may titrate or lower the dose of the antidepressant.⁵ If sexual dysfunction persists, clinicians may switch to an antidepressant with a lower incidence of sexual side effects.^5,7 Patients taking selective serotonin reuptake inhibitors (SSRIs), for example, have a higher incidence of sexual side effects compared with patients taking certain other antidepressant medications.^5,7 Other antidepressants, such as bupropion, which inhibit dopamine and norepinephrine reuptake, and duloxetine, which inhibits serotonin and norepinephrine reuptake, have a lower incidence of sexual side effects and may be considered as an alternate therapeutic option.^5,6,8

Another option is to use adjuvant therapy, such as phosphodiesterase type 5 (PDE5) inhibitor therapy, to help improve erectile function in men with antidepressant-induced ED.^5,9 My colleagues and I recently reported data that showed that tadalafil significantly improved erectile function in patients with ED taking antidepressant medication, including SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs).¹⁰ The study was a retrospective pooled analysis of 19 double-blind, placebo-controlled trials. Furthermore, the analysis demonstrated that tadalafil is efficacious in improving erectile function and safe in patients with ED who are taking antidepressants.

An earlier study indicated that sildenafil improves erectile function in men with antidepressant-associated ED.¹¹ This multicenter, 6-week, randomized, flexible-dose, double-blind, placebo-controlled trial focused on patients with SSRI-associated ED. Results confirmed previous reports that sildenafil improved SSRI-associated ED without the need to stop antidepressant therapy.

In addition to improving ED treatment outcomes in patients taking antidepressants, PDE5 inhibitors may also help patients with depression improve adherence to antidepressant therapy.¹² The results of a retrospective observational study analyzing treatment adherence determined by medication possession ratios suggested that treatment of ED with PDE5 inhibitors increased adherence to concomitant medication, including antidepressants, in patients who were previously nonadherent¹²; approximately 22% of patients nonadherent to antidepressant therapy became adherent after receiving their first prescription of a PDE5 inhibitor.

Given the abundant use of antidepressants, the high prevalence of depression, and associated sexual side effects that may be an unrecognized cause of nonadherence to antidepressant therapy, it is critical for clinicians to carefully monitor symptoms of depression and sexual dysfunction. Clinicians treating antidepressant-related ED can switch the antidepressant medication, adjust the dose, or add PDE5 inhibitor therapy to ameliorate both conditions and improve the quality of life and overall health of the patient.

References

1. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289:3095-3105.

2. Hing E, Cherry DK, Woodell DA. National Ambulatory Medical Care Survey: 2004 Summary. Hyattsville, MD: U.S. Department of Health & Human Services; 2006.

3. Rothschild AJ. Sexual side effects of antidepressants. J Clin Psychiatry. 2000;61(suppl 11):28-36.

4. Kennedy SH, Eisfeld BS, Dickens SE, Bacchiochi JR, Bagby RM. Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry. 2000;61:276-281.

5. Baldwin D, Mayers A. Sexual side-effects of antidepressant and antipsychotic drugs. Adv in Psychiatr Treatment. 2003;9:202-210.

6. Labbate LA, Croft HA, Oleshansky MA. Antidepressant-related erectile dysfunction: management via avoidance, switching antidepressants, antidotes, and adaptation. J Clin Psychiatry. 2003;64(suppl 10):11-19.

7. Coleman CC, Cunningham LA, Foster VJ, et al. Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment. Ann Clin Psychiatry. 1999;11:205-215.

8. Delgado PL, Brannan SK, Mallinckrodt CH, et al. Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder. J Clin Psychiatry. 2005;66:686-692.

9. Seidman S. Ejaculatory dysfunction and depression: pharmacological and psychobiological interactions [review]. Int J Impot Res. 2006;18:S33-S38.

10. Segraves RT, Lee J, Stevenson R, Walker DJ, Wang WC, Dickson RA. Tadalafil for treatment of erectile dysfunction in men on antidepressants. J Clin Psychopharmacol. 2007;27:62-66.

11. Fava M, Nurnberg HG, Seidman SN, et al. Efficacy and safety of sildenafil in men with serotonergic antidepressant-associated erectile dysfunction: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2006;67:240-246.

12. McLaughlin T, Harnett J, Burhani S, Scott B. Evaluation of erectile dysfunction therapy in patients previously nonadherent to long-term medications: a retrospective analysis of prescription claims. Am J Ther. 2005;12:605-611.