BLACK BOX WARNING
- suicidality in children, adolescents, and young adults
nortriptyline
Brand: Pamelor, Aventyl
⚠ BBW Beers Criteria TDM Required Prototype: amitriptyline
Drug Class: tricyclic antidepressant (TCA)
Drug Family: antidepressant
Subclass: secondary amine TCA
Organ Systems: cns
Mechanism of Action
Active demethylated metabolite of amitriptyline; inhibits norepinephrine and serotonin reuptake with greater selectivity for NET than SERT, producing relatively more noradrenergic effects. Less anticholinergic and sedating than amitriptyline due to reduced receptor binding breadth.
NET (norepinephrine transporter)SERT (serotonin transporter)muscarinic receptorsH1 histamine receptor
Indications
- major depressive disorder
- neuropathic pain
- migraine prophylaxis
- off-label: smoking cessation
- off-label: ADHD
Contraindications
- concurrent MAOI use
- acute post-MI recovery
- QT prolongation or bundle branch block
Adverse Effects
Common
- dry mouth
- constipation
- blurred vision
- orthostatic hypotension
- sedation (less than amitriptyline)
- tachycardia
Serious
- QT prolongation
- cardiac conduction disturbances
- seizures in overdose
- suicidal ideation
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~46-56% |
| Distribution | protein binding ~93-95%; highly lipophilic; large Vd |
| Metabolism | primarily via CYP2D6; CYP2D6 poor metabolizers have significantly higher plasma levels |
| Excretion | primarily renal as metabolites |
| Half-life | 18-44 hours (mean 31 hours) |
| Onset | antidepressant 2-4 weeks |
| Peak | 7-8.5 hours |
| Duration | 24 hours |
| Protein Binding | 93-95% |
| Vd | 12-57 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| MAOIs | serotonin syndrome and hypertensive crisis | contraindicated |
| CYP2D6 inhibitors | significantly increase nortriptyline levels | major |
| QT-prolonging agents | additive QT prolongation | major |
Nursing Considerations
- Nortriptyline has a narrow therapeutic window; plasma levels of 50-150 ng/mL are therapeutic, with toxicity at levels >500 ng/mL — TDM is recommended for dosing guidance.
- Preferred over amitriptyline in elderly patients requiring a TCA because it has less anticholinergic activity and fewer falls-related adverse effects, though still on Beers Criteria.
- Obtain baseline and periodic ECGs; QRS widening >110 ms or QTc >500 ms warrants dose reduction or discontinuation.
- Instruct patients to report palpitations, dizziness, or syncope immediately, as these may herald dangerous arrhythmias.
Clinical Pearls
- Nortriptyline is the preferred TCA for elderly patients when one is clinically necessary, as it has less orthostatic hypotension than amitriptyline and a more favorable tolerability profile.
- Its therapeutic drug monitoring window (50-150 ng/mL) is one of the few documented examples of a therapeutic concentration window — both too low (ineffective) and too high (toxic) are clinically harmful.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.