What is the recommended dosing for nortriptyline (tricyclic antidepressant)?

Nortriptyline Dosing

For depression in adults, start nortriptyline at 25 mg three to four times daily (or as a single daily dose), titrating gradually to a typical range of 75-100 mg/day, with plasma level monitoring recommended above 100 mg/day to maintain therapeutic concentrations of 50-150 ng/mL. 1

Standard Adult Dosing

• Initial dose: 25 mg three to four times daily, starting at a low level with gradual increases based on clinical response and tolerability 1
• Alternative regimen: The total daily dose may be administered once daily 1
• Typical therapeutic range: 75-100 mg/day for most patients 2
• Maximum dose: 150 mg/day; doses above this are not recommended 1
• Therapeutic plasma concentration: 50-150 ng/mL, which should be monitored when doses exceed 100 mg/day 1

Elderly Patient Dosing

Elderly patients require substantially lower doses: 30-50 mg/day in divided doses. 1

• Start at 10-25 mg at bedtime and increase gradually every 3-7 days to minimize side effects 2
• The frail elderly (average age 84) require an average dose of approximately 80 mg/day to achieve plasma levels of 100 ng/mL, though individual requirements vary by a factor of 20 3
• Elderly patients are more sensitive to anticholinergic effects (dry mouth, orthostatic hypotension, confusion, urinary retention) and require slower titration 2, 4
• Consider using a 25 mg test dose with 24-hour plasma level measurement to predict maintenance dose requirements and identify slow metabolizers early 5, 3

Neuropathic Pain Dosing

• Starting dose: 10-25 mg at bedtime 2, 4
• Titration: Increase by 25 mg every 3-7 days as tolerated 4
• Target range: 25-150 mg daily, typically at bedtime 4
• Adequate trial duration: 6-8 weeks, with at least 2 weeks at maximum tolerated dose 4
• Pain relief often occurs at lower doses than required for depression 4

Smoking Cessation Dosing

• Start at 25 mg before bed 10 days prior to quit day 6
• Titrate to 75 mg/day or maximal tolerated dose 6
• This indication showed significant cessation benefit (14% vs 3% at 6 months) despite frequent adverse effects including dry mouth (64%) 6

Critical Monitoring Requirements

Plasma level monitoring is mandatory when approaching or exceeding 100 mg/day to avoid toxicity while ensuring therapeutic efficacy. 1

• Optimal therapeutic window: 50-150 ng/mL 1, 5
• Higher concentrations are associated with increased adverse effects 1
• The active metabolite 10-hydroxynortriptyline accumulates more in elderly patients and can cause cardiotoxicity even when parent compound levels appear therapeutic 1
• ECG monitoring is recommended in patients over 40 years or with cardiac disease 4

Test Dose Strategy for Dose Prediction

A single test dose can predict maintenance requirements and prevent toxicity:

• 25 mg test dose (preferred in elderly): Measure plasma level at 24 hours 5, 3
• 24-hour levels correlate significantly with steady-state levels at 25 mg/day (r=0.71) and 50 mg/day (r=0.73) 3
• This approach is particularly valuable in elderly patients where nearly half of subjects on fixed doses of 50-100 mg/day had levels outside the therapeutic range 5
• A nomogram derived from regression equations can predict the dosage needed to achieve 50-150 ng/mL steady-state concentration 5

Common Pitfalls to Avoid

• Do not combine with amitriptyline: Nortriptyline is the active metabolite of amitriptyline, making combination pharmacologically redundant and increasing risk of serotonin syndrome and cardiac toxicity 2
• Do not rapidly escalate in elderly patients: They are highly sensitive to anticholinergic and cardiac effects 2, 1
• Do not assume fixed dosing works: Individual dose requirements vary by up to 20-fold, necessitating individualized titration 3
• Do not ignore cardiovascular contraindications: Both prolonged QTc and recent MI are contraindications 2

Drug Interactions Requiring Caution

• SSRIs (including sertraline): Risk of serotonin syndrome, particularly within 24-48 hours of dose increases; maintain intensive monitoring during transitions 7
• MAOIs: Contraindicated due to severe interaction risk 8
• Other serotonergic agents: Additive risk of serotonin syndrome 2

Advantages Over Amitriptyline

Nortriptyline is preferred over amitriptyline for neuropathic pain due to equivalent efficacy with superior tolerability, particularly fewer anticholinergic effects. 2

• Significantly fewer anticholinergic side effects (dry mouth, constipation, urinary retention, confusion) 2
• Better tolerated in elderly patients 2
• Less sedating than amitriptyline while maintaining equivalent efficacy for depression and neuropathic pain 2