Migraine prophylaxis
First line
Per AHS 2021 and 2012, amitriptyline is first-line for migraine prophylaxis. Dose 25–100 mg at bedtime. Efficacy comparable to propranolol and topiramate. Off-label per label (migraine indication not registered).
Tricyclic antidepressants (TCA)
ATC code: N06AA09 (Amitriptyline)
Brand names
Elavil, Endep
Non-selectively inhibits serotonin and norepinephrine reuptake in presynaptic neurons. Pronounced anticholinergic, antihistaminic, and α-adrenergic blockade explain side effects: dry mouth, constipation, urinary retention, orthostatic hypotension, sedation, weight gain. Cardiotoxic in overdose (quinidine-like sodium channel effect). Active metabolite: nortriptyline.
First line
Per AHS 2021 and 2012, amitriptyline is first-line for migraine prophylaxis. Dose 25–100 mg at bedtime. Efficacy comparable to propranolol and topiramate. Off-label per label (migraine indication not registered).
First line
First-line for neuropathic pain per NeuPSIG 2015, alongside gabapentinoids and SNRIs. Dose 25–75 mg at bedtime; start 10–25 mg and titrate. Pain effect emerges in 1–2 weeks at doses below antidepressant levels. Off-label per the Russian label, primary indication is depression. Side-effect profile limits use in elderly.
First line
Amitriptyline 10–50 mg at bedtime is a standard pharmacotherapy for fibromyalgia per 2017. Effects on sleep and pain are comparable to pregabalin and duloxetine. Off-label per Russian label.
Second line
In major depression, amitriptyline is effective, but the unfavorable side-effect profile and cardiotoxicity in overdose make it second-line after SSRIs/SNRIs per 2023 and NG222. Use is justified in patients with depression and concurrent chronic pain, insomnia, or migraine.
Boxed warning
FDA boxed warning: antidepressants increase suicidal ideation/behavior risk in children, adolescents, and adults under 25. Special monitoring in the first months and at dose changes.
FDA categories were retired in 2015 (historically C). Third-trimester use is associated with neonatal withdrawal syndrome. In pregnant patients with severe depression, continuation is individualized with a psychiatrist — untreated depression risk is significant for mother and fetus.
Transfers into milk in small amounts. Per LactMed, use is acceptable with infant sedation monitoring.
amitriptyline is evaluated for the following indications with varying evidence strength: Neuropathic pain (evidence tier A), Migraine prophylaxis (evidence tier A), Fibromyalgia (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of amitriptyline (≥ 1 in 100): Dry mouth, Sedation, drowsiness, Constipation, Weight gain, Orthostatic hypotension, dizziness, Urinary retention. See the Safety section for uncommon and serious reactions.
FDA categories were retired in 2015 (historically C). Third-trimester use is associated with neonatal withdrawal syndrome. In pregnant patients with severe depression, continuation is individualized with a psychiatrist — untreated depression risk is significant for mother and fetus.
Transfers into milk in small amounts. Per LactMed, use is acceptable with infant sedation monitoring.
amitriptyline is contraindicated in: Acute myocardial infarction; AV block, QT-prolonging arrhythmia; Acute intoxication with alcohol or other CNS depressants; Concurrent or recent (14 days) MAOI; Closed-angle glaucoma. Full list in the Safety section.
FDA boxed warning: antidepressants increase suicidal ideation/behavior risk in children, adolescents, and adults under 25. Special monitoring in the first months and at dose changes.