What is the effect of atomoxetine (Strattera) on libido in adult males?

Effect of Atomoxetine on Libido in Adult Males

Atomoxetine causes decreased libido in approximately 3% of adult male patients, representing a statistically significant increase compared to placebo (1%), and this sexual side effect should be explicitly discussed before initiating treatment. 1

Incidence and Clinical Significance

The FDA-approved prescribing information clearly documents that decreased libido occurs in 3% of atomoxetine-treated adult males versus 1% on placebo 1. This represents one of several sexual adverse effects that are more prominent in adult males compared to other populations:

• Adult males experience the highest burden of sexual side effects with atomoxetine, while female patients and adolescent male patients show profiles clinically similar to placebo 2
• Sexual dysfunction with atomoxetine is likely underreported because patients and physicians are often reluctant to discuss these issues 1
• The FDA label explicitly states that physicians should routinely inquire about sexual side effects during treatment, as standard adverse event reporting significantly underestimates their true incidence 1

Spectrum of Sexual and Genitourinary Effects in Adult Males

Beyond decreased libido, adult males on atomoxetine experience multiple related sexual adverse effects 1:

• Erectile dysfunction: 8.0% (vs 1.9% placebo)
• Ejaculation disorder/delayed ejaculation: 4% (vs 1.1% placebo)
• Urinary hesitation: 6.9% (vs 2.4% placebo)
• Dysuria: 3.7% (vs 1.5% placebo)
• Decreased urine flow: 2.5% (vs 0.6% placebo)

Time Course and Resolution

The onset and resolution patterns of sexual side effects follow a predictable timeline 2:

• Onset occurs early: Sexual dysfunction typically emerges during the second and third week of dosing 2
• Resolution is prolonged: Median time to resolution ranges from 3-8 weeks after event onset, depending on the specific adverse effect 2
• Discontinuation leads to rapid improvement: Genitourinary symptoms typically resolve within 2 days of stopping atomoxetine 3

Impact of CYP2D6 Metabolizer Status

Poor CYP2D6 metabolizers (approximately 7% of Caucasians) experience dramatically higher rates of sexual side effects 4, 1:

• Erectile dysfunction: 21% in poor metabolizers vs 9% in extensive metabolizers
• Ejaculation disorder: 6% in poor metabolizers vs 2% in extensive metabolizers
• Dry mouth: 35% in poor metabolizers vs 17% in extensive metabolizers (relevant as it reflects overall higher drug exposure)

This occurs because poor metabolizers have 10-fold higher drug exposure and a half-life of approximately 24 hours (versus much shorter in extensive metabolizers) 5.

Clinical Management Recommendations

Before initiating atomoxetine 1:

• Explicitly discuss the risk of decreased libido and other sexual side effects
• Document baseline sexual function
• Consider CYP2D6 genotyping if available, particularly in patients concerned about sexual side effects

During treatment 1:

• Routinely inquire about sexual function at each visit, as patients rarely volunteer this information
• Monitor for onset of symptoms during weeks 2-3 of treatment
• If sexual side effects emerge, consider dose reduction or switching to an alternative ADHD medication

If sexual dysfunction occurs 2, 3:

• Recognize that most events are not severe and discontinuation rates remain relatively low
• Understand that resolution may take 3-8 weeks even after dose adjustment
• Discontinuation leads to rapid resolution (typically within 2 days)

Important Caveats

The American College of Physicians notes that sexual dysfunction is generally underreported in antidepressant and related medication trials 6. The actual incidence of libido changes with atomoxetine may be higher than reported in clinical trials 1, 2. Additionally, concomitant use of CYP2D6 inhibitors (such as paroxetine, fluoxetine) can elevate atomoxetine levels and increase the risk of sexual side effects 4, 7.