What are the effects of Intuniv (guanfacine) 3 mg, Adderall (amphetamine and dextroamphetamine) 20 mg, and Prozac (fluoxetine) 30 mg, all taken orally once daily, on fertility?

Effects of Intuniv 3 mg, Adderall 20 mg, and Prozac 30 mg on Fertility

This medication combination may negatively impact fertility, particularly through fluoxetine's documented effects on sperm parameters and the potential for reduced fecundability in women, though the evidence is strongest for male fertility impairment.

Impact on Male Fertility

Fluoxetine (Prozac) Effects

• Fluoxetine has the most concerning fertility data among these three medications, with long-term use (60 days) in animal studies showing marked decreases in spermatogenesis, sperm motility, and sperm density 1
• Reproductive organ weights (testes, epididymides, ventral prostate, and seminal vesicles) were significantly decreased with chronic fluoxetine exposure 1
• Testosterone and FSH levels were significantly reduced in treated animals 1
• Male rats on fluoxetine demonstrated reduced ability to impregnate females, with decreased implantations and viable fetuses 1
• Multiple studies have associated fluoxetine specifically with gonadotoxic effects including decreased sperm concentration and motility, increased DNA fragmentation, and decreased reproductive organ weights 2
• The gonadotoxic effects appear to be reversible upon discontinuation 2

Amphetamine (Adderall) Effects

• The data on amphetamines and male fertility are extremely limited, with no robust human studies specifically examining fertility outcomes 3
• Animal studies have not demonstrated impairment of fertility at doses up to 12.5 mg/kg/day (approximately 1.5 times the maximum recommended human dose) 4

Guanfacine (Intuniv) Effects

• No adverse effects on fertility were observed in animal studies with guanfacine in male and female rats 5

Impact on Female Fertility

Fluoxetine (Prozac) Effects

• Women taking antidepressants while attempting to conceive showed reduced probability of conception in time-varying analyses (adjusted fecundability ratio 0.75; 95% CI, 0.53-1.06) 6
• When adjusting for history of depression, the association strengthened (adjusted FR 0.66; 95% CI, 0.45-0.97), and when restricting analysis to women with depression history (adjusted FR 0.64; 95% CI, 0.43-0.94) 6
• The mechanism may involve alteration of allopregnanolone levels, a neurosteroid important for fertility 6

Amphetamine (Adderall) Effects

• In animal reproduction studies, maternal exposure to 12 mg/kg/day during gestation resulted in increased stillborn pups, decreased pup weight, and increased pup deaths during the first 7 days postpartum 4
• No evidence of impaired fertility in adult animals at doses up to 12.5 mg/kg/day 4

Guanfacine (Intuniv) Effects

• No adverse fertility effects were observed in animal studies 5

Clinical Implications and Monitoring

For Patients Attempting Conception

• Consider discontinuing fluoxetine if fertility is a priority, as it has the strongest evidence for negative fertility effects, particularly in males 1, 2
• The effects of fluoxetine appear reversible, so a medication-free period or switch to an alternative with less fertility impact should be considered 2
• Amphetamines do not appear to significantly impair fertility based on available animal data, though human data are limited 4, 3
• Guanfacine appears to have the most favorable fertility profile of the three medications 5

Alternative Approaches

• For ADHD management, consider non-pharmacological approaches such as Dialectical Behavior Therapy (DBT), which has been modified for adults with ADHD and addresses concentration, disorganization, interpersonal relationships, and emotion regulation 7
• If antidepressant therapy cannot be discontinued, consider alternatives to SSRIs, though data on other classes are limited and conflicting 2, 8

Important Caveats

• The distinction between medication effects versus underlying psychiatric condition effects on fertility is difficult to establish, as depression and ADHD themselves may impact fertility through stress hormone effects on the hypothalamic-pituitary-gonadal axis 8
• Most fertility data come from animal studies or small human cohorts, limiting generalizability 1, 2
• Long-term neurodevelopmental effects of these medications on offspring have not been adequately studied 3