Nortriptyline
PAMELOR
Pronunciation: nor-TRIP-ti-leen
“North-tripping Pam”
What it isNorepinephrine-predominant tricyclic reuptake inhibitor; depression and neuropathic pain.
Why it mattersThe best-tolerated tricyclic — less anticholinergic and less orthostatic than amitriptyline, and it has a defined therapeutic level range.
What it changesStill lethal in overdose from sodium channel blockade. CYP2D6 substrate; it is the active metabolite of amitriptyline.
Pearls
- Therapeutic level roughly 50–150 ng/mL.
- Helps Parkinson depression but risks falls and cognitive impairment.
- Off-label migraine preventive.
Nortriptyline prescription history
Animated chart of estimated U.S. prescriptions per year, Antidepressants (1957–2026). Nortriptyline enters in 1964 (estimated).
FDA-approved for
- depression (~1964)
Off-label
- neuropathic pain
- smoking cessation
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityAnticholinergic effects and cardiac sodium-channel blockade make overdose rapidly life-threatening.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Depression | Adult | 25 mg TID or QID (or total daily dose QD) | plasma level 50–150 ng/mL | 150 mg/day |
| Depression | Elderly / adolescent | 30–50 mg/day in divided doses or QD | plasma level 50–150 ng/mL | 150 mg/day |
Renal Undefined
Hepatic Undefined
Instructions
- Oral; initiate low and increase gradually per response/tolerance
- Reduce dose for minor side effects; discontinue promptly for serious/allergic reactions
- After remission, maintain at lowest dose that sustains remission
- Monitor plasma levels when dose >100 mg/day
- Not recommended for children
Available strengths
- cap 10, 25, 50, 75 mg
- sol 10 mg/5 mL
Contraindications
- MAOIs (concurrently or within 14 days) due to risk of serotonin syndrome
- During the acute recovery period after myocardial infarction
Cautions
- Clinical worsening and suicide risk, especially early in treatment and after dose changes
- Not approved in pediatric patients
- Cardiovascular effects (arrhythmia, conduction changes) — caution post-MI
- Anticholinergic effects; caution with urinary retention, narrow-angle glaucoma
- May lower seizure threshold
Adverse reactions
- Anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention)
- Orthostatic hypotension, tachycardia, arrhythmias
- Sedation, tremor, confusion (especially elderly)
- Weight changes, nausea
Pregnancy Safe use not established; weigh benefit vs risk. Animal studies inconclusive.
Lactation Undefined
Cost
Generic entry1992
Serotonicity
This drug is routinely called serotonergic. By Gillman’s human-effect criteria it does not raise serotonin in the synapse.
Potent NRI with negligible SRI activity; no Gillman-type serotonin-toxicity mechanism.
Label contraindicationMAOIs (concurrently or within 14 days) due to risk of serotonin syndrome. The label governs prescribing; Gillman’s point concerns serotonin toxicity only.
It binds the serotonin transporter, and its SERT peg is drawn to that textbook affinity. The pale halo around the peg marks binding that, by Gillman’s human-effect criteria, does not produce clinical serotonin reuptake inhibition.
Gillman’s four human testsA measurable SERT affinity that fails all four is not clinical serotonicity.
- Retarded orgasm
- Efficacy in OCD and cataplexy
- Clonus and hyperreflexia in single-drug overdose
- Serotonin toxicity when combined with an MAOI
Non-elevating actionNone recorded
Evidence confidenceHigh
Background: what serotonicity is · what is and is not an SRI · what counts as a relevant MAOI.
Open Nortriptyline in the interactive console ↗
Memory aids: interaction avatars
Open Nortriptyline in the interactive console ↗
Self-check
- How does nortriptyline compare with amitriptyline’s anticholinergic burden?
Less anticholinergic. - What mechanism makes nortriptyline overdose lethal?
Sodium-channel blockade.