What anti-anxiety medications, such as selective serotonin reuptake inhibitors (SSRIs), have a minimal risk of causing infertility?

Anti-Anxiety Medications and Infertility Risk

Most anti-anxiety medications commonly used, including SSRIs and benzodiazepines, do not have strong evidence of causing permanent infertility, though SSRIs may temporarily reduce fertility parameters in males and potentially delay time to conception in females. 1, 2

Medications with Minimal Infertility Risk

Benzodiazepines

• Alprazolam and other benzodiazepines have demonstrated efficacy for anxiety treatment without documented effects on fertility parameters. 3
• These medications are effective anxiolytics that do not appear in the literature as causing reproductive dysfunction 3

SSRIs - Overall Safety Profile

While SSRIs are widely used for anxiety disorders, the fertility impact requires nuanced understanding:

For Female Patients:

• SSRIs appear safe for women undergoing fertility treatment, with multiple observational studies showing no significant negative impact on IVF outcomes. 1
• The benefit of treating depression/anxiety in infertile women may outweigh theoretical fertility concerns 1
• However, fluoxetine specifically deserves caution, as it was associated with 24% reduced fecundability and significantly lower live birth rates in prospective cohort data. 4
• Paroxetine and escitalopram showed experimental concerns regarding fallopian tube motility, though clinical significance remains unclear 1

For Male Patients:

• SSRIs may cause reversible, dose-dependent adverse effects on sperm parameters (count, motility, morphology). 1
• Six of seven studies found adverse impacts on semen quality, though effects appear reversible upon discontinuation 2
• A 2024 retrospective study of 299 men found no significant differences in sperm liquefaction, motility, viscosity, or count between SSRI users and non-users, though this conflicts with earlier data 5
• For men actively trying to conceive, consider alternative agents like mirtazapine or bupropion, which have lower potential for sexual and fertility side effects. 1

Specific SSRI Recommendations by Fertility Concern

Lower Concern Options:

• Sertraline, citalopram, and escitalopram - These have moderate evidence profiles with less consistent negative fertility associations 3, 2
• Paroxetine - While effective for anxiety, has some experimental concerns but mixed clinical data 1

Higher Concern Options:

• Fluoxetine should be avoided in women actively trying to conceive given prospective evidence of reduced fecundability and live birth rates 4
• All SSRIs warrant caution in males with active fertility goals due to potential sperm parameter effects 1

Clinical Algorithm for Medication Selection

Step 1: Assess fertility timeline

• If pregnancy planned within 3-6 months: Consider benzodiazepines for short-term use or non-SSRI alternatives 3
• If no immediate fertility plans: SSRIs remain appropriate first-line agents 3

Step 2: Gender-specific considerations

• Males trying to conceive: Avoid SSRIs; use mirtazapine or bupropion 1
• Females trying to conceive: Avoid fluoxetine specifically; sertraline or escitalopram may be reasonable if anxiety/depression treatment is essential 4
• Females undergoing IVF with depression/anxiety: SSRIs are justified and may improve outcomes by treating psychiatric symptoms 1

Step 3: Monitor and adjust

• SSRI effects on male fertility appear reversible, typically within 3 months of discontinuation 1
• If conception does not occur within expected timeframe, reassess medication contribution 2

Important Caveats

• The evidence quality is limited by retrospective designs, small sample sizes, and conflicting results across studies. 2, 5
• Depression and anxiety themselves may impair fertility independent of medication effects 6
• Pregnancy loss and neonatal complications are separate concerns from fertility - SSRIs carry FDA warnings for third-trimester complications including persistent pulmonary hypertension of the newborn 7
• Cognitive-behavioral therapy and exercise represent effective non-pharmacologic alternatives for mild-moderate anxiety 6
• Close monitoring for suicidality is required when initiating SSRIs, particularly in patients under 24 years of age, though the absolute risk is low (NNH = 143). 3