Which benzodiazepines (BZDs) and sedatives have the lowest incidence of sexual dysfunction in men?

Benzodiazepines and Sedatives with Lowest Incidence of Sexual Dysfunction in Men

Bupropion, mirtazapine, and nefazodone have the lowest incidence of sexual dysfunction among sedative medications, while benzodiazepines like diazepam, alprazolam, and lorazepam appear to have lower rates of sexual dysfunction compared to clonazepam. 1, 2

Incidence of Sexual Dysfunction by Medication Class

Benzodiazepines

• Clonazepam: Has a significantly higher rate of sexual dysfunction (42.9%) compared to other benzodiazepines, primarily causing erectile dysfunction 2
• Diazepam, alprazolam, and lorazepam: Associated with lower rates of sexual dysfunction compared to clonazepam 2

Sedative Antidepressants

• Lowest sexual dysfunction rates:

  • Moclobemide: 3.9%
  • Amineptine: 6.9%
  • Nefazodone: 8%
  • Mirtazapine: 24.4% 1

• Highest sexual dysfunction rates:

  • SSRIs (fluoxetine, sertraline, paroxetine, citalopram): 58-73%
  • Venlafaxine: 67.3% 1, 3

Types of Sexual Dysfunction

Sexual dysfunction from these medications can manifest as:

• Decreased libido
• Erectile dysfunction
• Ejaculatory problems (delayed, retrograde, or dry ejaculation)
• Orgasmic difficulties
• Decreased sexual satisfaction 4, 5

Mechanism of Action

• Benzodiazepines: Sexual dysfunction is primarily related to enhanced GABA-A receptor function, which can reduce penile erection 6
• SSRIs and SNRIs: Sexual dysfunction is related to increased serotonergic activity 3
• Medications with lower sexual side effects: Generally work through dopaminergic or adrenergic systems rather than primarily serotonergic mechanisms 3

Management Strategies for Sexual Dysfunction

If sexual dysfunction occurs with necessary medication:

1. Consider medication switch to agents with lower sexual side effect profiles:

   • For anxiety/insomnia: Consider diazepam, alprazolam, or lorazepam instead of clonazepam 2
   • For depression with sedative properties: Consider mirtazapine, nefazodone, bupropion, or moclobemide 1, 5

2. Adjunctive treatments for erectile dysfunction:

   • PDE5 inhibitors (sildenafil, tadalafil) if not contraindicated 4
   • Testosterone therapy if total morning testosterone <300 ng/dL 4

3. For ejaculation/orgasm problems:

   • Vibratory therapy
   • Pelvic physical therapy 4

Important Considerations and Pitfalls

• Sexual dysfunction is often underreported unless specifically asked about by clinicians 1, 5
• Sexual dysfunction significantly impacts quality of life and medication adherence 5
• Psychological factors often coexist with medication-induced sexual dysfunction and may require additional treatment 4
• Always consider cardiovascular risk before prescribing treatments for erectile dysfunction 4, 7
• Avoid PDE5 inhibitors in patients taking nitrates due to risk of dangerous hypotension 4, 7

Algorithm for Medication Selection

1. For anxiety/insomnia requiring benzodiazepines:

   • First-line: Diazepam, alprazolam, or lorazepam
   • Avoid: Clonazepam when sexual function is a concern

2. For depression requiring sedative effects:

   • First-line: Mirtazapine, nefazodone, or bupropion
   • Avoid: SSRIs, SNRIs, and TCAs when sexual function is a concern

3. For treating existing sexual dysfunction:

   • Erectile dysfunction: PDE5 inhibitors (if not contraindicated)
   • Ejaculation/orgasm issues: Consider SSRIs (paroxetine, sertraline) for premature ejaculation; vibratory therapy for delayed orgasm
   • Low desire: Consider testosterone therapy if levels are low