What are the FDA-approved medications for mood dysregulation in menopause, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)?

FDA-Approved Medications for Mood Dysregulation in Menopause

While there are no FDA-approved SSRIs or SNRIs specifically indicated for mood dysregulation in menopause, several antidepressants are recommended for managing menopausal symptoms including mood changes. 1

First-Line Non-Hormonal Options

• SSRIs and SNRIs are recommended by the American College of Physicians as effective first-line non-hormonal pharmacological options for women experiencing menopausal symptoms who cannot or prefer not to use hormonal treatments 1
• These medications can help manage both vasomotor symptoms and mood disturbances that commonly occur during menopause 2

Recommended SSRIs:

• Paroxetine: Low-dose paroxetine (7.5 mg daily) significantly reduces both frequency and severity of vasomotor symptoms and decreases nighttime awakenings 3

  • For controlled-release formulations, 12.5 mg is considered the optimal dose 2, 3
  • Important caution: Should be used with caution in women taking tamoxifen as it inhibits CYP2D6, potentially reducing tamoxifen's effectiveness 3, 1

• Citalopram: May help with sleep disturbances in menopausal women, though long-term studies show limited effect on vasomotor symptoms 2, 4

• Fluoxetine: Has shown some benefit for mood symptoms in menopausal women, but long-term studies show limited efficacy for vasomotor symptoms 4

• Sertraline: Has shown benefit in tamoxifen users for reducing hot flashes, though results can be variable 2, 5

Recommended SNRIs:

• Venlafaxine: The SNRI venlafaxine (starting at 37.5 mg daily, increasing to 75 mg daily after 1 week) is extensively studied and considered safe and effective for menopausal symptoms 2, 6
  • Preferred SNRI for women on tamoxifen as it has minimal interaction with CYP2D6 1
  • Side effects include dry mouth, nausea, constipation, and decreased appetite 2, 6

Comparative Efficacy and Side Effects

• SSRIs/SNRIs have side effects including dry mouth, nausea, constipation, headache, and sexual dysfunction with a 10-20% discontinuation rate 2, 1
• Adverse events that may occur with SSRIs include:
  • Nausea, insomnia, sexual dysfunction, fatigue, dizziness, tremor, somnolence, sweating, dry mouth, decreased energy, diarrhea, and constipation 7
• SNRIs like venlafaxine may cause increased cholesterol, sweating, and changes in sleep habits 6

Special Considerations

• For women with a history of breast cancer:

  • Avoid paroxetine and fluoxetine in women taking tamoxifen 3, 1
  • Venlafaxine is the preferred SNRI for women on tamoxifen 1
  • Gabapentin is also a good alternative for breast cancer survivors 1

• For women with sexual dysfunction concerns:

  • Consider gabapentin over SSRIs/SNRIs if sexual dysfunction is a concern 1

Treatment Algorithm

1. Initial Assessment:

   • Evaluate severity of mood symptoms and presence of other menopausal symptoms 2, 1
   • Screen for contraindications to specific medications 3, 1

2. First-line Treatment:

   • For women NOT on tamoxifen:
     • Start with low-dose paroxetine (7.5 mg daily) or venlafaxine (37.5 mg daily) 3, 1
   • For women on tamoxifen:
     • Venlafaxine is preferred (37.5 mg daily, increasing to 75 mg after one week) 1

3. Dose Adjustment:

   • Evaluate response after 4 weeks 3
   • If inadequate response with minimal side effects, increase dose gradually:
     • Paroxetine CR: increase to 12.5 mg 3
     • Venlafaxine: increase to 75 mg daily 2, 6

4. Monitoring and Maintenance:

   • Continue effective treatment as needed with periodic reassessment 3
   • Taper gradually when discontinuing to minimize withdrawal symptoms 2, 3

Additional Non-Pharmacological Options

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

Important Caveats

• Most SSRIs and SNRIs are not FDA-approved specifically for menopausal mood symptoms, though they are commonly prescribed off-label for this purpose 2
• Sertraline is FDA-approved for premenstrual dysphoric disorder, which may be relevant for perimenopausal women 5
• The optimal duration of treatment is unknown; medications should be tapered gradually when discontinuing 2
• Individual response varies significantly, with some women experiencing an exacerbation of symptoms 2