TaperCommunitynortriptyline
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Nortriptyline is a secondary amine tricyclic antidepressant and the active metabolite of amitriptyline. It is used for major depressive disorder and off-label for neuropathic pain, migraine prophylaxis, and smoking cessation. It is better tolerated than amitriptyline with fewer anticholinergic and sedative effects.
10mg, 25mg, 50mg, 75mg
Capsules: 10mg, 25mg, 50mg, 75mg; Oral solution: 10mg/5mL
Category D (positive evidence of risk)
Primarily inhibits norepinephrine reuptake, with lesser serotonin reuptake inhibition. Has less anticholinergic, antihistaminic, and alpha-adrenergic blocking activity compared to tertiary amine TCAs like amitriptyline.
Available in capsule and liquid forms. Less anticholinergic than amitriptyline.
Oral solution (10mg/5mL) available for gradual reductions. Less sedating than amitriptyline, withdrawal may be milder.
Toxicity
Cardiotoxic in overdose (QRS widening, arrhythmias), though less toxic than amitriptyline. Therapeutic drug monitoring recommended (therapeutic window 50–150 ng/mL).
Pharmacokinetics
Well absorbed after oral administration. Bioavailability ~46–70%. Tmax 3–12 hours. Food does not significantly affect absorption.
~21 L/kg
Hepatic via CYP2D6 (primary) to 10-hydroxynortriptyline and other hydroxylated metabolites. Also metabolized by CYP2C19 and CYP3A4.
Renal (~40% as metabolites) with ~2% unchanged in urine. Fecal excretion minor.
~93–95%
~500 mL/min (apparent oral clearance, highly variable depending on CYP2D6 status)
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