Can amitriptyline and Topamax (topiramate) be taken together?

Amitriptyline and Topiramate Can Be Safely Taken Together for Migraine Prevention

Yes, amitriptyline and topiramate (Topamax) can be safely taken together with appropriate monitoring, and this combination may provide better outcomes for migraine prevention than either medication alone. 1

Pharmacological Interaction and Safety

The FDA drug label for topiramate specifically addresses this combination, stating: "There was a 12% increase in AUC and Cmax for amitriptyline (25 mg per day) in 18 normal subjects receiving 200 mg/day of topiramate." 2 This means:

• Some patients may experience increased amitriptyline blood levels when taking topiramate
• Dose adjustments should be based on clinical response rather than plasma levels
• No absolute contraindication exists for using these medications together

Evidence Supporting Combination Therapy

Research demonstrates that combining these medications can be beneficial:

• A double-blind randomized controlled trial found that the combination of amitriptyline and topiramate resulted in higher patient satisfaction compared to either drug alone 1
• The combination therapy showed fewer side effects with a lower amount of amitriptyline needed 1
• Particularly beneficial for patients with migraine and comorbid depression 1

Dosing Considerations

When using these medications together:

• Start with lower doses of each medication and titrate slowly
• For amitriptyline: Start at 10-25 mg daily and increase gradually to 10-100 mg daily 3
• For topiramate: Start at lower doses (25 mg) and gradually increase to 50-100 mg daily 3
• Monitor for side effects and efficacy at regular intervals

Potential Side Effects to Monitor

Amitriptyline-specific concerns:

• Anticholinergic effects (dry mouth, constipation, urinary retention)
• Sedation and drowsiness
• Orthostatic hypotension
• Cardiac effects (QT prolongation in higher doses) 4

Topiramate-specific concerns:

• Cognitive effects (confusion, difficulty concentrating)
• Paresthesia (tingling sensations)
• Metabolic acidosis
• Kidney stones
• Weight loss 2

Combined therapy concerns:

• Increased sedation
• Cognitive impairment
• Dizziness
• Potential for additive weight effects (topiramate causing weight loss, amitriptyline causing weight gain) 5

Special Populations and Contraindications

Pregnancy and breastfeeding:

• Topiramate is contraindicated in pregnancy due to teratogenic effects 3
• Amitriptyline may be used under specialist supervision if benefits outweigh risks 3

Cardiovascular concerns:

• Monitor blood pressure and heart rate, especially in patients with pre-existing cardiovascular disease 5
• Amitriptyline should be used with caution in patients with cardiac conditions 4

Other contraindications:

• Avoid in patients with glaucoma (both medications can exacerbate) 3, 5
• Use caution in patients with kidney stones (topiramate increases risk) 2
• Avoid in patients taking monoamine oxidase inhibitors (MAOIs) 4

Clinical Approach to Combination Therapy

1. Assess baseline symptoms and document frequency, severity, and duration of migraines
2. Start with one medication first (typically amitriptyline) at a low dose
3. Add the second medication (topiramate) if response is inadequate after 4-8 weeks
4. Titrate doses slowly to minimize side effects
5. Monitor regularly for efficacy and adverse effects
6. Adjust doses based on clinical response rather than standard dosing

Bottom Line

The combination of amitriptyline and topiramate can be effective for migraine prevention, particularly in patients with comorbid depression. While there is a pharmacokinetic interaction that may increase amitriptyline levels, this combination can be safely used with appropriate monitoring and dose adjustments based on clinical response.