Nortin

Approved Indications:

• Major Depressive Disorder (MDD), including endogenous and psychotic depression
• Relief of neuropathic pain (off-label but commonly used)
• Prophylaxis of migraine headaches (off-label)
• Nocturnal enuresis in children (off-label)
• Attention-deficit hyperactivity disorder (ADHD) adjunct therapy (off-label)

Adults (Depression):

• Initial: 25 mg orally 3–4 times daily or 75 mg once daily (preferably at bedtime)
• Maintenance: 50–100 mg/day in divided doses or single dose at night
• Max dose: 150 mg/day (under specialist supervision)
• Dose should be titrated gradually based on clinical response and tolerability

Elderly/Debilitated:

• Initial: 10–25 mg at bedtime
• Maintenance: 30–50 mg/day
• Monitor for anticholinergic and cardiovascular side effects

Pediatrics (≥6 years, Enuresis):

• 10–20 mg at bedtime for children 6–11 years
• 25–35 mg at bedtime for children 11–16 years
• Use only when non-pharmacologic treatments have failed

Renal/Hepatic Impairment:

• Use with caution; dose adjustment may be necessary especially in hepatic impairment

Nortriptyline is a tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin into presynaptic nerve terminals, thereby increasing their availability in the central nervous system. It also exhibits anticholinergic, antihistaminic, and alpha-adrenergic blocking activities, which contribute to its therapeutic effects and side-effect profile. The increase in neurotransmitters improves mood and alleviates neuropathic pain by modulating pain pathways.

• Absorption: Well absorbed orally with peak plasma concentration reached in 4–8 hours
• Bioavailability: Approximately 45–65% due to first-pass metabolism
• Distribution: Widely distributed; ~92% protein-bound
• Metabolism: Extensively metabolized in the liver, mainly by CYP2D6 to active metabolite desmethylnortriptyline
• Half-life: 16–90 hours (average ~36 hours); prolonged in elderly and poor metabolizers
• Excretion: Primarily renal elimination of metabolites

• Pregnancy: Category C – Animal studies have shown adverse effects; human data limited. Use only if benefits outweigh risks.
• Lactation: Excreted in breast milk in small amounts; considered compatible with breastfeeding but monitor infants for sedation or irritability.

• Tricyclic Antidepressant (TCA)
• Secondary amine TCA (primarily norepinephrine reuptake inhibition)

• Hypersensitivity to nortriptyline or TCAs
• Recent myocardial infarction
• Concomitant or recent (within 14 days) use of MAO inhibitors
• Severe cardiac conduction abnormalities
• Acute recovery phase post-myocardial infarction

• Risk of suicidality in young adults and adolescents; monitor carefully
• May cause QT prolongation and arrhythmias; caution in cardiac disease
• Anticholinergic effects (dry mouth, constipation, urinary retention) may be pronounced in elderly
• Lowers seizure threshold; avoid in epilepsy or seizure-prone patients
• Risk of serotonin syndrome with concurrent serotonergic drugs
• Monitor for withdrawal symptoms if discontinued abruptly

Common: Drowsiness, dry mouth, dizziness, constipation, blurred vision, weight gain, orthostatic hypotension
Serious (rare): Cardiac arrhythmias, seizures, hepatic dysfunction, mania, severe allergic reactions

• MAO inhibitors: Risk of hypertensive crisis and serotonin syndrome; contraindicated
• CYP2D6 inhibitors (e.g., fluoxetine): Increased nortriptyline levels and toxicity
• Other CNS depressants: Additive sedation
• Anticholinergic drugs: Enhanced side effects
• Drugs causing QT prolongation: Increased risk of arrhythmias

• APA guidelines: TCAs reserved for treatment-resistant depression or specific indications due to side effect profile
• AAN guidelines: Nortriptyline recognized as effective for neuropathic pain and migraine prophylaxis
• FDA: Enhanced warnings on suicidality risk in patients under 25 years

• Store at 20–25°C (68–77°F)
• Protect from moisture and light
• Keep out of reach of children
• Oral solutions should be shaken well before use and discarded after 30 days