What treatment options are available for a patient, regardless of age or sex, experiencing non-hormonal hot flashes, potentially caused by anxiety, certain medications like selective serotonin reuptake inhibitors (SSRIs) or other medical conditions?

Treatment of Non-Hormonal Hot Flashes

For non-hormonal hot flashes regardless of underlying cause, start with venlafaxine 37.5-75 mg daily or gabapentin 900 mg daily as first-line pharmacologic therapy, as these have the strongest evidence for efficacy and safety. 1

First-Line Pharmacologic Options

SNRIs (Preferred Initial Choice)

• Venlafaxine is the most effective non-hormonal medication, reducing hot flash severity by approximately 60-61% compared to placebo 1, 2
• Start at 37.5 mg daily, increase to 75 mg after 1 week if greater symptom control is needed 1, 3
• Response occurs faster than with other agents 1
• Side effects include dry mouth, decreased appetite, nausea, constipation, and possible sexual dysfunction, but these are dose-dependent 1
• Taper gradually when discontinuing to minimize withdrawal symptoms 1, 4

Anticonvulsants (Equally Effective Alternative)

• Gabapentin 900 mg daily reduces hot flash severity by 46% at 8 weeks 1
• Particularly useful when given at bedtime for patients with sleep disturbance from hot flashes 1
• Side effects include somnolence and fatigue 1
• Pregabalin is an alternative anticonvulsant option 1, 3

Second-Line Pharmacologic Options

SSRIs (Use with Caution)

• Paroxetine 7.5 mg daily reduces both frequency and severity of hot flashes and decreases nighttime awakenings 4
• Controlled-release formulation at 12.5 mg achieves 62% reduction in hot flash composite scores 4
• Critical caveat: Paroxetine strongly inhibits CYP2D6 and should NOT be used in patients taking tamoxifen, as it blocks conversion to active metabolites 1, 4, 3
• Citalopram 10-20 mg daily reduces hot flashes by 50-58% and has weak CYP2D6 inhibition, making it safer for tamoxifen users 4, 5, 6
• Fluoxetine has the weakest efficacy among SSRIs and should be avoided in tamoxifen users 4, 3

Clonidine

• The alpha-agonist antihypertensive clonidine can reduce hot flash frequency and severity 1
• May have slower onset but better tolerability than venlafaxine 1
• Side effects include sleep difficulties, dry mouth, fatigue, dizziness, and nausea 1

Non-Pharmacologic Interventions

Evidence-Based Options

• Acupuncture has been shown equivalent to or better than venlafaxine or gabapentin in multiple studies 1
• Cognitive behavioral therapy (CBT) reduces the perceived burden of hot flashes 1
• Clinical hypnosis may provide benefit 4
• Lifestyle modifications: avoid spicy foods, caffeine, and alcohol; maintain cool room temperature; dress in layers 1
• Weight loss if overweight or obese 1

Limited or Mixed Evidence

• Yoga improves quality of life but evidence for hot flash reduction is mixed 1
• Exercise/physical activity has inconclusive evidence 1
• Vitamin E (800 IU daily) shows marginal benefit with mixed results 1, 2
• Black cohosh, phytoestrogens, and botanical supplements have limited or mixed data 1

Treatment Algorithm for Non-Hormonal Hot Flashes

1. Assess severity and impact on quality of life 1

   • Mild symptoms not interfering with sleep or function: behavioral modifications and lifestyle changes 2
   • Moderate to severe symptoms: proceed to pharmacologic therapy

2. First-line pharmacologic choice 1

   • If NOT on tamoxifen: Venlafaxine 37.5 mg daily, increase to 75 mg after 1 week OR Gabapentin 900 mg daily at bedtime
   • If on tamoxifen: Venlafaxine 37.5-75 mg daily (preferred) OR Gabapentin 900 mg daily OR Citalopram 10-20 mg daily 4, 6, 3

3. Evaluate response after 4 weeks 4

   • If inadequate response with minimal side effects: increase dose or switch agents
   • If intolerable side effects: switch to alternative agent

4. Consider adding non-pharmacologic therapies at any stage 1

   • Acupuncture, CBT, or hypnosis can be used alone or in combination with medications

5. Continue effective treatment as needed with periodic reassessment 4

   • Taper gradually when discontinuing SNRIs or SSRIs 1, 4

Critical Pitfalls to Avoid

• Never use paroxetine or fluoxetine in patients taking tamoxifen due to potent CYP2D6 inhibition 1, 4, 3
• Do not abruptly discontinue SNRIs or SSRIs—always taper gradually 1, 4
• Avoid clonidine, methyldopa, and belladonna due to modest efficacy and adverse effects 2
• Do not use hormonal therapies (estrogen/progestins) in patients on risk reduction therapy or with breast cancer history 1
• Monitor blood pressure when using SNRIs, particularly in hypertensive patients 6