TCAs for Migraine Prevention and ADHD Treatment
Tricyclic antidepressants (TCAs), specifically amitriptyline, are effective for migraine prevention but not for ADHD treatment, while lamotrigine has no established role in either condition.
TCAs for Migraine Prevention
Amitriptyline is the only TCA with consistent evidence for migraine prevention and should be used at 30-150 mg/day. 1 This represents the highest level of evidence (Level A) with support from multiple class I trials. 1
Key Clinical Points for Migraine:
- Amitriptyline is particularly superior in patients with mixed migraine and tension-type headache compared to beta-blockers like propranolol. 1
- Other TCAs (nortriptyline, protriptyline, doxepin, clomipramine, imipramine) have no evidence supporting their use in migraine prevention. 1
- Common side effects include drowsiness, weight gain, dry mouth, sedation, constipation, and anticholinergic symptoms. 1
- Caution: TCAs that cause weight gain should be avoided in patients with idiopathic intracranial hypertension presenting with migraine-like headaches. 1
Dosing Algorithm for Amitriptyline in Migraine:
- Start at 10-25 mg at bedtime 2, 3
- Titrate slowly over 3-4 months to reach therapeutic range of 30-150 mg/day 1
- Allow 3 months at therapeutic dose to assess efficacy 1
- The sedating effect can benefit patients with comorbid insomnia 2
TCAs for ADHD: Not Recommended as Primary Treatment
TCAs are second-line agents for ADHD only when stimulants fail or are contraindicated, and they are less effective than stimulants for core ADHD symptoms. 4, 5
Evidence for TCAs in ADHD:
- TCAs are superior to placebo for ADHD behavioral symptoms but none are as effective as psychostimulants for treating attentional and cognitive symptoms. 5
- They can help reduce impulsive and hyperactive behavior but have limited effect on attention and cognition. 5
- Desipramine should be avoided in youth, adolescents, and possibly adults due to cardiac safety concerns. 5
- Side effects include sedation, dry mouth, and constipation. 4
When to Consider TCAs for ADHD:
- Only after stimulant failure with both amphetamine and methylphenidate (75-90% respond to stimulants) 4
- When tics preclude stimulant use 4
- When severe appetite loss or marked insomnia from stimulants is intolerable 4
Lamotrigine: No Role in Either Condition
Lamotrigine has no established evidence for treating either ADHD or migraine prevention. The guidelines reviewed anticonvulsants extensively and found good evidence only for divalproex sodium and sodium valproate in migraine prevention. 1 Lamotrigine was not mentioned as having efficacy for either condition.
Anticonvulsants with Evidence for Migraine:
- Divalproex sodium and sodium valproate have Level A evidence for migraine prevention. 1
- Topiramate has Level A evidence and may help with weight loss, though it carries risks of depression and cognitive slowing. 1
- Gabapentin has limited evidence (Level U - inadequate data). 1
- Carbamazepine and vigabatrin are ineffective for migraine. 1
Comorbid ADHD and Migraine: Treatment Strategy
When both conditions coexist, treat them as separate entities:
- For ADHD: Use stimulants as first-line (methylphenidate or amphetamine). 4, 5
- For migraine prevention: Use amitriptyline 30-150 mg/day if TCAs are chosen, though beta-blockers (propranolol 80-240 mg/day) or anticonvulsants (divalproex sodium) are also Level A options. 1
- If stimulants cause insomnia that worsens migraine: Consider adding clonidine 0.05-0.1 mg at bedtime to counteract stimulant-induced sleep disruption. 6, 7
Critical Pitfall to Avoid:
Do not use TCAs as monotherapy expecting to treat both ADHD and migraine effectively. 8 While amitriptyline treats migraine well, it will not adequately address ADHD core symptoms of inattention and cognitive dysfunction. 5 Treatment with one antidepressant alone often does not suffice to treat both disorders effectively. 8