What non-hormonal medications are used to treat menopausal symptoms?

Non-Hormonal Medications for Menopausal Symptoms

For women experiencing menopausal symptoms who cannot or prefer not to use hormonal treatments, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentin, and clonidine are effective first-line non-hormonal pharmacological options. 1

First-Line Non-Hormonal Options

SSRIs/SNRIs

• Low-dose paroxetine (7.5 mg daily) significantly reduces both frequency and severity of vasomotor symptoms and decreases nighttime awakenings 2
• For controlled-release formulations of paroxetine, 12.5 mg is considered the optimal dose 1, 2
• Venlafaxine (37.5 mg daily, increasing to 75 mg daily after 1 week) is extensively studied and effective for vasomotor symptoms 1, 3
• Other effective SSRIs include citalopram and escitalopram 3, 4
• The mechanism of action appears to be independent and more rapid than their antidepressant effect 2
• SSRIs/SNRIs reduce hot flash frequency by approximately 40-65% compared to 75% with hormonal treatments 4

Gabapentin

• Effective alternative first-line treatment for hot flashes 1
• Particularly useful when sexual dysfunction is a concern before or during SSRI/SNRI therapy 1
• Common side effects include dizziness, drowsiness, and unsteadiness 1

Clonidine

• Centrally acting α-adrenergic agonist with mild to moderate efficacy in treating menopausal hot flashes 1
• Can reduce hot flashes by up to 46% 1
• Available in oral (0.1 mg/day) and transdermal formulations 1
• Common side effects include dry mouth, insomnia or drowsiness 1

Comparative Efficacy and Side Effects

Efficacy Comparison

• Mean reduction in daily hot flashes versus placebo 1:
  • Clonidine: -0.95
  • SSRIs/SNRIs: -1.13
  • Gabapentin: -2.05

Side Effects

• SSRIs/SNRIs: Dry mouth, nausea, constipation, headache, sexual dysfunction (10-20% discontinuation rate) 1, 2
• Gabapentin: Dizziness, drowsiness, unsteadiness (10% discontinuation rate) 1
• Clonidine: Dry mouth, insomnia or drowsiness (40% discontinuation rate) 1
• Side effects are typically transient, dose-related, and milder at lower doses used for hot flash treatment 1, 2

Special Considerations

Breast Cancer Survivors

• Avoid paroxetine and fluoxetine in women taking tamoxifen, as these drugs inhibit CYP2D6, blocking the conversion of tamoxifen to active metabolites 1, 2
• Venlafaxine is the preferred SNRI for women on tamoxifen 2, 3
• Gabapentin is also a good option for breast cancer survivors 1

Treatment Algorithm

1. Start with lowest effective dose of selected medication 3
2. Evaluate response after 4 weeks (if no response by then, treatment is unlikely to be effective) 1, 2
3. If first-line treatment fails, consider switching to another class of medication 1
4. For persistent symptoms, consider combination therapy, though adding gabapentin to SSRI/SNRI has not shown additional benefit 1

Additional Non-Pharmacological Options

• Lifestyle modifications: Rhythmic breathing, avoiding spicy foods, caffeine, and alcohol 1
• Environmental modifications: Cool rooms, dressing in layers 1
• Acupuncture: May reduce menopausal symptoms in some women 1
• Cognitive behavioral therapy and clinical hypnosis may provide benefit 2

Treatment of Other Menopausal Symptoms

Vaginal Dryness

• Low-dose vaginal estrogen tablets or estradiol vaginal ring may be recommended for urogenital atrophy, though safety in breast cancer survivors is not well established 1
• Vaginal dilators or pelvic floor relaxation techniques may help with dyspareunia secondary to vaginal atrophy 1

Sexual Dysfunction

• Psychoeducational support, sexual counseling, and marital counseling should be offered to women with sexual complaints 1
• Consider gabapentin over SSRIs/SNRIs if sexual dysfunction is a concern 1

Non-hormonal medications offer effective alternatives for women who cannot or choose not to use hormone therapy for menopausal symptoms, with SSRIs/SNRIs, gabapentin, and clonidine providing significant relief for many women.