Amitriptyline
Elavil
Tricyclic AntidepressantGeneric availableTDM data
Clinical Pharmacology Amitriptyline hydrochloride is an antidepressant with sedative effects. Its mechanism of action in man is not known. It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. This interference with reuptake of norepinephrine and/or serotonin is believed to underlie the antidepressant activity of amitriptyline.
Compare Amitriptyline →FDA-Approved Indications
- depression
Common Off-Label Uses
- Neuropathic pain
- Migraine prophylaxis
- Tension headache prophylaxis
- Fibromyalgia
- Insomnia
- Irritable bowel syndrome
- Interstitial cystitis
What Sets This Drug Apart
- Most anticholinergic TCA and among the most sedating (alongside doxepin); top-tier efficacy in NMA data (Cipriani response OR among highest) but second-line due to side-effect burden
- Extensive off-label pain use: migraine prophylaxis, neuropathic pain, fibromyalgia, and IBS — often the first TCA tried for chronic pain syndromes
- Highest weight gain among TCAs (Pillinger #2 after maprotiline); 46% of patients gain ≥2 kg vs 19% placebo
- Active metabolite nortriptyline (secondary amine) has its own therapeutic profile; at steady state, plasma is a mixture of both compounds
- Multiple CYP substrate (2D6, 2C19, 1A2, 3A4) with moderate CYP2D6 inhibition — high drug interaction potential
- Cardiovascular toxicity is class-defining: contraindicated in acute post-MI recovery; mandatory baseline ECG
Boxed Warning
Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality)