What can be done for a patient on lamotrigine (Lamictal) and duloxetine (Cymbalta) who is experiencing worsening night sweats and hot flashes after starting lamotrigine?

Management of Night Sweats/Hot Flashes in a Patient on Lamotrigine and Duloxetine

Start venlafaxine 37.5 mg daily (increasing to 75 mg after 1 week if needed) or gabapentin 900 mg daily to reduce vasomotor symptoms by 46-61%, as these are the most effective non-hormonal first-line treatments for moderate to severe hot flashes and night sweats. 1, 2

Primary Treatment Approach

First-Line Pharmacologic Options

• Venlafaxine (SNRI) is recommended at 37.5 mg daily, escalating to 75 mg after 1 week if greater symptom control is needed, reducing hot flash severity by up to 61% 1, 2
• Gabapentin at 900 mg daily reduces hot flashes by 46-51% compared to 26-31% with placebo, and is the only non-hormonal treatment demonstrating efficacy equivalent to estrogen 1, 3
• Both medications have similar efficacy in direct comparative studies, though 68% of patients prefer venlafaxine over gabapentin 3, 1

Duloxetine Consideration

• The patient is already on duloxetine (Cymbalta), which is an SNRI like venlafaxine 4
• Duloxetine itself can cause night sweats as a side effect, particularly when combined with other medications 4
• Alpha-adrenergic blockers may reduce night sweats in patients taking serotonin reuptake inhibitors like duloxetine 4

Evaluation of Lamotrigine as Contributing Factor

Temporal Relationship Assessment

• The patient reports worsening symptoms after starting lamotrigine, suggesting a temporal association 2
• Lamotrigine is not typically associated with vasomotor symptoms in the literature reviewed 5, 6
• However, investigate whether lamotrigine initiation coincided with other medication changes or medical conditions 2

Rule Out Other Causes

• Hormonal status: Determine if the patient is perimenopausal or postmenopausal, as this is the primary cause of hot flashes in 81% of cases 2
• Concurrent medications: Check for tamoxifen or aromatase inhibitors if there is breast cancer history 2
• Medical conditions: Evaluate thyroid function and diabetes as alternative causes of vasomotor symptoms 1
• Duloxetine contribution: Consider that the SNRI may be contributing to or exacerbating night sweats 4

Treatment Algorithm

Step 1: Add Gabapentin or Venlafaxine

• If sleep disruption is prominent: Use gabapentin 900 mg at bedtime, as anticonvulsants cause somnolence and are particularly useful for hot flashes disturbing sleep 3
• If daytime symptoms predominate: Use venlafaxine 37.5-75 mg daily 1, 2
• Evaluate response after 4 weeks and monitor for side effects, particularly in the first week 1

Step 2: Monitor for Side Effects

• Gabapentin: Watch for somnolence and dizziness, which cause withdrawal in fewer patients than SNRIs 3
• Venlafaxine: Monitor for asthenia, constipation, dry mouth, nausea, dizziness, insomnia, and somnolence, which lead to 10-20% treatment discontinuation 3
• Taper gradually when discontinuing SNRIs to minimize withdrawal symptoms 3

Step 3: Consider Duloxetine Adjustment

• If symptoms persist despite adding gabapentin or venlafaxine, consider whether duloxetine is contributing to night sweats 4
• Switching from duloxetine to a different antidepressant with lower propensity for sweating may be warranted if vasomotor symptoms remain refractory 4

Important Caveats

Medication Interactions

• Avoid paroxetine and fluoxetine if the patient is on tamoxifen, as they inhibit CYP2D6 and block tamoxifen conversion to active metabolites 1, 2
• Venlafaxine and citalopram have minimal effects on tamoxifen metabolism and are preferred alternatives 2

Lamotrigine Dosing Considerations

• If lamotrigine is coadministered with valproate or carbamazepine, dosage adjustments are required 5
• Ensure lamotrigine was titrated appropriately over 6 weeks to 200 mg/day to minimize risk of serious rash 5

When to Reassess

• If symptoms persist after 4 weeks of adequate treatment, investigate other causes including thyroid disease and diabetes 1
• Consider that the combination of duloxetine and lamotrigine may have additive effects on thermoregulation, though this is not well-documented 4