Introduction

Sexual dysfunction is common among individuals with major depressive disorder. For instance, a study by Kennedy and colleagues[1] revealed that of 134 patients with major depression surveyed, 40% of men and 50% of women reported decreased sexual interest; 40% to 50% of the sample also reported reduced levels of arousal. Sexual dysfunction is also a common side effect of antidepressant treatment, particularly pharmacotherapy with serotonin reuptake inhibitors (SRIs). Treatment-emergent SRI-induced sexual dysfunction ranges from approximately 30% to 70% of patients treated for depression.[2-4] Bupropion (Wellbutrin) and nefazodone (Serzone) is no longer on the market), in contrast, are associated with lower rates of sexual dysfunction.^[2]

Antidepressant-induced sexual dysfunction becomes an important issue in the context of treatment effectiveness, as antidepressant medications are helpful only insofar as patients take them. Intolerable side effects may be one reason that patients are noncompliant with antidepressant treatment.^[5] Given the important clinical implications of premature discontinuation -- for example, higher rates of relapse and recurrence -- increasing attention is currently being devoted to the management of antidepressant-induced sexual dysfunction and other unwanted side effects of pharmacotherapy for depression.

The issue of sexual functioning in the context of depression was discussed by a number of clinical researchers at the 156th annual meeting of the American Psychiatric Association in San Francisco, California. Topics included a comparison of the rates of treatment-emergent sexual dysfunction across various SRI antidepressants as well as strategies for managing antidepressant-induced sexual dysfunction, such as adding as-needed sildenafil to SRI pharmacotherapy for remitted depressed patients.

Assessment and Risk Factors for Sexual Dysfunction in the Context of Major Depression

The sexual response cycle consists of 4 phases: desire, arousal, orgasm, and resolution, and, as explained by Anita Clayton, MD,^[6] Professor and Vice Chairman, Department of Psychiatric Medicine, University of Virginia, Charlottesville, the phases of the sexual response cycle are affected by reproductive hormones and neurotransmitters.

For example, according to Dr. Clayton, estrogen, testosterone, and progesterone promote sexual desire; dopamine promotes desire and arousal, and norepinephrine promotes arousal. Prolactin inhibits arousal, and oxytocin promotes orgasm. Serotonin, in contrast to most of these other molecules, appears to have a negative impact on the desire and arousal phases of the sexual response cycle, and this seems to occur through its inhibition of dopamine and norepinephrine. Serotonin also appears to exert peripheral effects on sexual functioning by decreasing sensation and by inhibiting nitric oxide. The serotonergic system, therefore, may contribute to various sexual problems across the sexual response cycle.

Dr. Clayton recommended that clinicians conduct a thorough assessment with patients when attempting to ascertain the etiology of sexual dysfunction. Factors to consider include primary sexual disorders, such as hypoactive sexual desire disorder, as well as secondary causes, such as psychiatric disorders (eg, depression) and endocrine disorders (eg, diabetes mellitus, which may cause neurologic and/or vascular complications). Physicians should also inquire about situational and psychosocial stressors (eg, relationship conflict and job changes), as well as the use of substances known to exert a negative impact upon sexual functioning, such as psychotropic medication and drugs of abuse, such as alcohol.

Antidepressant-induced sexual dysfunction is common but underreported. For instance, only 14.2% of depressed patients taking selective SRIs (SSRIs) for depression spontaneously report sexual complaints; however, if queried directly, nearly 60% of patients report sexual complaints.^[7] Using standardized instruments, such as the Arizona Sexual Experiences Scale (ASEX) and the Changes in Sexual Functioning Questionnaire (CSFQ-C), and asking phase-specific questions may facilitate the clinicians' assessment of patients' sexual dysfunction.

There are a number of patient risk factors for sexual dysfunction. These include age (being 50 years old or older), having less than a college education, not being employed full-time, tobacco use (6-20 times per day), a prior history of antidepressant-induced sexual dysfunction, a history of little or no sexual enjoyment, and considering sexual functioning as "not" or only "somewhat" important..^[2] Gender, race, and duration of treatment, in contrast, do not appear to predict sexual dysfunction.

Clinicians may employ several strategies to manage antidepressant-induced sexual dysfunction.^[4] One is waiting for tolerance to develop, although, according to Dr. Clayton, this is typically not successful, as only a small portion of patients report improvement in sexual functioning over time during SSRI pharmacotherapy.^[7,8] Another option is to reduce the current dose, but this may result in subtherapeutic doses of medication. Drug holidays may provide relief from SSRI-induced sexual dysfunction,^[9] but, cautioned Dr. Clayton, may result in SSRI discontinuation symptoms after 1 to 2 days or encourage medication noncompliance.

The use of sildenafil (Viagra), bupropion (Wellbutrin), yohimbine, or amantadine may be helpful as antidotes, but, as yet, these agents are not indicated specifically for this use.^[4,10] Switching to antidepressants with little risk of inducing sexual dysfunction -- for example, bupropion, mirtazapine, and nefazodone (no longer on market) -- may be a successful strategy for some patients,^[3,11,12]] although there is the risk that depressive symptoms may not respond as well to the second agent as they did to the first.

References