Nortriptyline
Pamelor
Tricyclic AntidepressantGeneric availableTDM data
Clinical Pharmacology The mechanism of mood elevation by tricyclic antidepressants is at present unknown. Nortriptyline hydrochloride is not a monoamine oxidase inhibitor. It inhibits the activity of such diverse agents as histamine, 5-hydroxytryptamine, and acetylcholine. It increases the pressor effect of norepinephrine but blocks the pressor response of phenethylamine. Studies suggest that nortriptyline hydrochloride interferes with the transport, release, and storage of catecholamines.
Compare Nortriptyline →FDA-Approved Indications
- depression
Common Off-Label Uses
- Neuropathic pain
- Migraine prophylaxis
- Smoking cessation
- ADHD
- Chronic pain
What Sets This Drug Apart
- Best-tolerated TCA: secondary amine with lower anticholinergic, sedation, and orthostatic burden than tertiary amines (amitriptyline, imipramine)
- Often considered first-line TCA for both depression and chronic pain when a tricyclic is chosen
- Well-established therapeutic window (50-150 ng/mL) — one of the few antidepressants where both subtherapeutic and supratherapeutic levels predict poor response
- Active metabolite of amitriptyline; preferred when the parent compound's anticholinergic burden is limiting
- Second-line noradrenergic option for smoking cessation (evidence base) and ADHD (off-label)
- CYP2D6 substrate with only weak CYP2D6 inhibition — fewer drug interactions than most TCAs
Boxed Warning
Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality)