Can amitriptyline (tricyclic antidepressant) worsen migraines?

Amitriptyline and Migraines: Potential for Worsening

Amitriptyline does not typically worsen migraines; rather, it is recommended as a second-line preventive treatment for migraine with evidence supporting its efficacy in reducing migraine frequency. 1

Evidence for Amitriptyline in Migraine Prevention

Amitriptyline has been extensively studied as a preventive treatment for migraines:

• It is listed as a second-line medication for migraine prevention in current guidelines 1
• Recommended dosage ranges from 10-100 mg orally at night 1
• Clinical trials have shown efficacy at doses of 30-150 mg/day 1
• Moderate certainty evidence indicates amitriptyline increases the proportion of patients experiencing a 50% or more reduction in monthly migraine days compared to placebo 2

Mechanism and Effectiveness

Amitriptyline works through several mechanisms that may help prevent migraines:

• Tricyclic antidepressants like amitriptyline have been a mainstay in prophylactic therapy of migraine 3
• Among antidepressants, amitriptyline has been more frequently studied and has the most consistent support for efficacy in migraine prevention 1
• One trial comparing propranolol and amitriptyline suggested that amitriptyline was superior for patients with mixed migraine and tension-type headache 1

Potential Side Effects (Not Worsening)

While amitriptyline doesn't typically worsen migraines, it does have side effects to consider:

• Drowsiness, weight gain, and anticholinergic symptoms are frequently reported 1
• There is moderate certainty evidence that amitriptyline increases the proportion of patients who discontinue due to adverse events compared to placebo (50 more per 1,000) 2
• Common side effects include dry mouth 4
• Contraindications include age <6 years, heart failure, co-administration with monoamine oxidase inhibitors and SSRIs, and glaucoma 1

Clinical Application

When considering amitriptyline for migraine prevention:

1. Start with a low dose (10mg) and titrate slowly upward
2. Allow adequate trial period (2-3 months) before determining efficacy 1
3. Monitor for side effects, particularly anticholinergic symptoms
4. Consider as second-line therapy after first-line options (beta-blockers, topiramate, candesartan) 1

Important Caveats

• Despite widespread use, some researchers note that conclusive studies regarding amitriptyline's efficacy in migraine are still needed 5
• The robust placebo response in some studies has complicated assessment of amitriptyline's true efficacy 6
• Amitriptyline appears particularly effective for patients with both migraine and depression, or those with mixed migraine and tension-type headache 1, 3

In clinical practice, while individual responses may vary, there is no evidence in the medical literature suggesting that amitriptyline typically worsens migraines. On the contrary, it remains a recommended preventive treatment option with moderate evidence supporting its efficacy.