What alternative antidepressant can be used for an adult female patient with no significant medical history, experiencing anger, shaking, and hot flashes while taking Lexapro (escitalopram)?

Switching from Lexapro for Anger, Shaking, and Hot Flashes

Switch to venlafaxine 37.5 mg daily, increasing to 75 mg after one week, or alternatively to sertraline 50 mg daily if the patient prefers to avoid SNRIs. 1, 2

Primary Recommendation: Venlafaxine

Venlafaxine is the most extensively studied and effective alternative for managing hot flashes while providing antidepressant effects. 1

• Start at 37.5 mg daily and increase to 75 mg after one week if greater symptom control is needed 1
• Reduces hot flash frequency and severity by approximately 61% compared to 27% with placebo 1
• Has rapid onset of efficacy and is generally well tolerated 1
• Side effects include dry mouth, reduced appetite, nausea, and constipation, which increase with higher doses 1
• Must be tapered gradually on discontinuation to prevent withdrawal symptoms 1

Alternative Option: Sertraline

Sertraline 50 mg daily is a reasonable alternative, particularly if the patient experienced activation symptoms (anger, agitation) on escitalopram. 1, 2

• Superior to placebo in reducing hot flashes 1, 2
• Has weak or no effects on CYP2D6 enzyme 1, 2
• Mixed results with substantial individual variability in response 1, 2
• Must be tapered gradually to prevent discontinuation symptoms 2
• May not affect quality of life measures as robustly as other options 1

Why Not Continue Escitalopram

The symptoms described (anger, shaking, hot flashes) represent a combination of:

• Activation syndrome (anger, agitation) - common with SSRIs, particularly escitalopram 1
• Tremor - a recognized adverse effect of SSRIs 1
• Hot flashes - which escitalopram has shown inconsistent efficacy in treating 3, 4

Research shows escitalopram at 10-20 mg/day is not consistently effective for hot flashes, with one study showing only 14.4% reduction versus 6.7% increase with placebo 4, while another showed no significant effects whatsoever 4.

Additional Considerations

If Antidepressants Are Insufficient

Gabapentin 900 mg daily is highly effective for hot flashes and does not cause sexual dysfunction or have drug interactions. 1

• Reduces hot flashes by 46-49% compared to 15-21% with placebo 1
• Side effects (dizziness, drowsiness) typically resolve after the first week 1
• No withdrawal syndrome unlike SSRIs/SNRIs 1
• Can be taken at bedtime if somnolence occurs 1

Critical Caveat About Drug Selection

If the patient is taking tamoxifen (common in breast cancer patients with hot flashes), avoid paroxetine and fluoxetine entirely, as they strongly inhibit CYP2D6 and reduce tamoxifen efficacy. 1 Venlafaxine, sertraline, and citalopram have minimal CYP2D6 effects and are preferred 1, 2.

Monitoring Response

• Assess efficacy within 4 weeks; if no response by then, the treatment is unlikely to be effective 1
• Common adverse effects (nausea, dizziness) affect 63% of patients on second-generation antidepressants but are typically mild and transient 1
• Discontinuation due to adverse effects occurs in 10-20% of patients on SSRIs/SNRIs 1