Nortriptyline
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Tricyclic antidepressant (TCA, secondary amine), Antidepressant, Neuropathic pain medicine, Migraine prophylactic
Nortriptyline (hydrochloride)
Pamelor (US brand discontinued; generic widely available), Aventyl
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Summary
Classes
Common uses
Major depressive disorder (FDA)0, Neuropathic pain, often first-line (off-label; diabetic peripheral neuropathy, postherpetic neuralgia)0, Migraine prophylaxis (off-label)0, Chronic pain syndromes (off-label)0, Smoking cessation adjunct (off-label, modest evidence)0
Pharmacy
Starting dose
Depression: 25 mg PO TID-QID or 75 mg at bedtime, titrate to 75-150 mg/day. Neuropathic pain: 10-25 mg at bedtime, titrate to 50-100 mg/day. Elderly: 10 mg at bedtime (Beers-list cautions, though less than amitriptyline)
Preparations
Capsules 10, 25, 50, 75 mg; oral solution 10 mg/5 mL
US FDA Max
150 mg/day; therapeutic plasma-level monitoring recommended (target 50-150 ng/mL window)
Pharmacology
Routes
Oral
Onset
Pain and migraine prophylaxis effect 1-4 weeks; antidepressant effect 4-6 weeks
Duration
24 hours (HS dosing)
Half-life
18-44 hours[2]
Bioavailability
~50% (oral)[2]
Pregnancy
TCA class signal; limited human data specific to nortriptyline.[citation needed]
Legal status
Purported mechanism
Secondary amine TCA, the active metabolite of amitriptyline, with substantially less anticholinergic, antihistaminergic, and α1-adrenergic activity than the parent compound. This makes nortriptyline the "cleaner" TCA, generally preferred over amitriptyline in elderly patients and in chronic pain where the tertiary-amine side-effect burden is undesirable. Selective norepinephrine reuptake inhibition predominates over serotonin reuptake inhibition.0 Therapeutic plasma-level monitoring is standard practice for TCAs given the narrow therapeutic index and the established plasma-level-efficacy correlation. CYP2D6 substrate; CPIC PGx guidance applies for dose individualization[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, Pamelor (nortriptyline hydrochloride), Mallinckrodt/various, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/018012s029,018013s059lbl.pdf