Amitriptyline
Amitriptyline (hydrochloride)
Elavil (US brand discontinued; generic widely available), Endep, Tryptizol
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Summary
Classes
Common uses
Major depressive disorder (FDA; historical; now usually reserved for treatment-refractory cases due to safety profile)0, Neuropathic pain (off-label, often first-line)0, Migraine prophylaxis (off-label, frequently first-line)0, Tension-type headache prophylaxis (off-label)0, Fibromyalgia (off-label)0, Irritable bowel syndrome (off-label)0, Pediatric nocturnal enuresis (FDA, historical)0
Pharmacy
Starting dose
Depression (rarely used now): 25-75 mg PO at bedtime, titrate to 150 mg/day. Neuropathic pain / migraine prophylaxis: 10-25 mg at bedtime, titrate by 10-25 mg weekly to 50-100 mg/day. Elderly: 10 mg at bedtime (Beers-list cautions apply)
Preparations
Tablets 10, 25, 50, 75, 100, 150 mg
US FDA Max
300 mg/day (historical hospitalized inpatient depression); 150 mg/day outpatient typical ceiling
Pharmacology
Routes
Oral
Onset
Sleep effect from first dose; analgesic and migraine-prophylaxis effect 1-4 weeks; antidepressant effect 4-6 weeks
Duration
24 hours (HS dosing)
Half-life
Amitriptyline 10-50 hours (highly variable); nortriptyline active metabolite 18-44 hours[2]
Bioavailability
~50% (oral)[2]
Pregnancy
Older agent with substantial use experience; observational signals not clearly causal.[citation needed]
Legal status
Purported mechanism
Tricyclic antidepressant inhibiting both serotonin and norepinephrine reuptake (the antidepressant and analgesic mechanism), with substantial additional muscarinic-acetylcholine M1 antagonism, H1 antihistaminergic activity, and α1-adrenergic antagonism. These ancillary activities drive the sedation, weight gain, dry mouth, constipation, orthostatic hypotension, and the Beers-list anticholinergic-burden concerns in elderly patients.0 Active metabolite nortriptyline is itself a separately marketed TCA with somewhat less anticholinergic burden. CYP2D6 and CYP2C19 substrate; CPIC PGx guidance applies for dose individualization. TCAs are lethal in overdose from sodium-channel-blockade-induced cardiac arrhythmias (wide QRS, torsades, cardiac arrest), the primary reason TCAs have been displaced from first-line antidepressant use by the safer SSRI alternatives[1].
References
- ↑ CPIC Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants, 2016. https://cpicpgx.org/guidelines/guideline-for-tricyclic-antidepressants-and-cyp2d6-and-cyp2c19/
- ↑ 2.0 2.1 2.2 FDA Prescribing Information, Elavil (amitriptyline hydrochloride), Merck/various, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/085966s095,085969s084,085968s096,085972s062,085974s075,085976s061,085971s072,085967s094lbl.pdf