Amitriptyline: Difference between revisions

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{{MedTemplate

| generic = Amitriptyline

| generic = Amitriptyline (hydrochloride)

| brand = Elavil

| brand = Elavil (US brand discontinued; generic widely available), Endep, Tryptizol

| classes = TCA, Antidepressant

| structure =

| mechanism = ~~Serotonin~~ and norepinephrine reuptake ~~inhibitor~~; ~~anticholinergic~~

| classes = [[:Category:Tricyclic antidepressants|Tricyclic antidepressant (TCA)]], [[:Category:Antidepressants|Antidepressant]], [[:Category:Migraine prophylactics|Migraine prophylactic]], [[:Category:Neuropathic pain medicines|Neuropathic pain medicine]]

| uses = <vote slug="major-depressive-disorder-amitriptyline-use">Major depressive disorder (FDA; historical; now usually reserved for treatment-refractory cases due to safety profile)</vote>, <vote slug="neuropathic-pain-amitriptyline-use">Neuropathic pain (off-label, often first-line)</vote>, <vote slug="migraine-prophylaxis-amitriptyline-use">Migraine prophylaxis (off-label, frequently first-line)</vote>, <vote slug="tension-headache-prophylaxis-use">Tension-type headache prophylaxis (off-label)</vote>, <vote slug="fibromyalgia-amitriptyline-use">Fibromyalgia (off-label)</vote>, <vote slug="irritable-bowel-syndrome-use">Irritable bowel syndrome (off-label)</vote>, <vote slug="nocturnal-enuresis-pediatric-use">Pediatric nocturnal enuresis (FDA, historical)</vote>

| 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

| fda_max = 300 mg/day (historical hospitalized inpatient depression); 150 mg/day outpatient typical ceiling

| pill_id =

| 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)

| halflife = Amitriptyline 10-50 hours (highly variable); nortriptyline active metabolite 18-44 hours<ref name="elavil-label">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</ref>

| bioavailability = ~50% (oral)<ref name="elavil-label" />

| pregnancy = Older agent with substantial use experience; observational signals not clearly causal.{{citation needed}}

| legal = [[USLegal:Prescription only|Rx-only]] in US. Carries the antidepressant '''Boxed Warning''' for suicidality in children, adolescents, and young adults<ref name="elavil-label" />

| mechanism = <vote slug="amitriptyline-mech-claim">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.</vote> 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<ref name="cpic-tca">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/</ref>.

}}

== References ==

[[Category:Tricyclic antidepressants]]

[[Category:Antidepressants]]

[[Category:Migraine prophylactics]]

[[Category:Neuropathic pain medicines]]

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