Nortriptyline
PAMELOR
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.
FDA-approved for
- depression (~1964)
Off-label
- neuropathic pain
- smoking cessation
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
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
⚠ BOXED WARNING
- Suicidal thoughts and behaviors in patients under 25
Cost, est. cash$5–$150/month
Generic entry1992
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityAnticholinergic effects and cardiac sodium-channel blockade make overdose rapidly life-threatening.
Mechanism of action: Nortriptyline ballicule
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