Can selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs) be used to manage hot flashes in menopausal women?

SSRIs and SNRIs for Managing Hot Flashes in Menopausal Women

SSRIs and SNRIs are effective first-line non-hormonal treatments for managing hot flashes in menopausal women, with venlafaxine and paroxetine showing the strongest evidence for efficacy and tolerability. 1, 2

First-Line Treatment Options

• Venlafaxine (SNRI) is recommended as first-line therapy at 37.5 mg daily, increasing to 75 mg daily after 1 week if symptoms persist, with demonstrated efficacy in reducing hot flashes by 61% compared to 27% with placebo 2
• Paroxetine (SSRI) at low doses (7.5 mg daily for immediate release or 12.5 mg for controlled release) significantly reduces both frequency and severity of vasomotor symptoms 3, 4
• Both medications have rapid onset of action (within 1 week) and can reduce hot flashes by up to 65% 5

Efficacy and Mechanism

• SSRIs/SNRIs reduce the mean daily number of hot flashes by approximately 1.13 more than placebo 1
• The mechanism appears independent of and more rapid than the antidepressant effect 3
• Median reductions of 62.2% for 12.5 mg paroxetine CR and 64.6% for 25.0 mg paroxetine CR have been observed compared to 37.8% for placebo 4

Treatment Algorithm

1. Initial selection:

   • For women with concurrent depression/anxiety: Start with venlafaxine 37.5 mg daily 2
   • For women without concurrent mood symptoms: Consider paroxetine 7.5 mg daily 3

2. Dose titration:

   • If using venlafaxine, increase to 75 mg daily after 1 week if symptoms persist 1, 2
   • If using paroxetine, increase to 20 mg daily after 1 week if symptoms persist 1

3. Assessment of response:

   • Evaluate efficacy after 4 weeks; if no response, treatment is unlikely to be effective 1, 3
   • If first agent is ineffective, consider switching to the alternative (venlafaxine to paroxetine or vice versa) 1

Important Considerations and Contraindications

• Tamoxifen interaction: Paroxetine and fluoxetine should be avoided in women taking tamoxifen as they inhibit CYP2D6, blocking conversion to active metabolites 1, 3, 2
• For tamoxifen users: Venlafaxine, citalopram, or escitalopram are preferred alternatives 3, 6
• Contraindications: SSRIs/SNRIs are contraindicated in women taking monoamine oxidase inhibitors 1
• Caution: Use with caution in women with bipolar disorder due to risk of inducing mania 1

Side Effects and Management

• Common side effects include dry mouth, blurred vision, sexual dysfunction, nausea, and constipation 1, 6
• Side effects are typically mild, transient, and dose-related; lower doses used for hot flashes tend to have fewer side effects than those used for depression 1
• Discontinuation rates due to side effects range from 10-20% in clinical trials 1
• Taper gradually when discontinuing to prevent withdrawal symptoms, especially with short-acting SSRIs like paroxetine 3, 2

Alternative Options

• If SSRIs/SNRIs are ineffective or not tolerated, gabapentin (900 mg/day) is an effective alternative that reduces hot flash severity by 46% compared to 15% with placebo 1, 2
• Gabapentin may be particularly beneficial for patients whose sleep is disturbed by hot flashes due to its sedative effects 2
• Clonidine can be considered for mild to moderate hot flashes, especially in women with concurrent hypertension 1, 2

Comparative Efficacy

• Among SSRIs, paroxetine, citalopram, and escitalopram show the strongest evidence for efficacy 7, 5
• Among SNRIs, venlafaxine and desvenlafaxine are most effective 7, 8
• Fluoxetine and sertraline appear less effective and should be considered second-line options 8, 5