What is the recommended dosage and usage of Nortriptyline (tricyclic antidepressant) for treating major depressive disorder and chronic pain?

Nortriptyline Dosing and Usage

For neuropathic pain, start nortriptyline at 25 mg at bedtime and titrate by 25 mg every 3-7 days as tolerated to a maximum of 150 mg/day, maintaining plasma levels between 50-150 ng/mL; for major depressive disorder, use the same titration schedule but consider 25 mg 3-4 times daily dosing, with an adequate trial requiring 6-8 weeks including at least 2 weeks at maximum tolerated dose. 1, 2

Dosing for Neuropathic Pain

Starting and Titration:

• Begin at 25 mg at bedtime 1
• Increase by 25 mg every 3-7 days as tolerated 1
• Maximum dose: 150 mg/day 1, 2
• Duration of adequate trial: 6-8 weeks with at least 2 weeks at maximum tolerated dose 1

Therapeutic Monitoring:

• Target plasma concentration: 50-150 ng/mL 1, 2
• If blood concentration of nortriptyline plus its metabolite is <100 ng/mL, continue cautious titration 1
• Doses above 150 mg/day are not recommended 2

Dosing for Major Depressive Disorder

Standard Adult Dosing:

• Start at 25 mg 3-4 times daily 2
• Alternative: Give total daily dose once daily 2
• Usual range: 75-100 mg/day in divided doses 2
• Maximum: 150 mg/day (doses above this are not recommended) 2

Treatment Duration:

• Continue for 4-9 months after satisfactory response for first episode 1
• For patients with 2 or more episodes, longer duration is beneficial 1
• Assess therapeutic response within 1-2 weeks of initiation 1
• Modify treatment if inadequate response by 6-8 weeks 1

Special Population Considerations

Elderly Patients:

• Start at 30-50 mg/day in divided doses 2
• Use lower starting doses (approximately 50% of adult dose) 1
• Nortriptyline is preferred over amitriptyline in elderly due to fewer anticholinergic effects 1, 3
• Monitor for orthostatic hypotension, confusion, and anticholinergic effects 3

Plasma Level Monitoring:

• Essential when doses exceed 100 mg/day 2
• Optimal response associated with 50-150 ng/mL 2
• Higher concentrations may increase adverse effects 2
• Elderly patients may have higher levels of active metabolite 10-hydroxynortriptyline, which can cause cardiotoxicity even when nortriptyline levels are therapeutic 2

Clinical Monitoring Algorithm

Initial Phase (Weeks 1-2):

• Assess patient status, therapeutic response, and adverse effects within 1-2 weeks 1
• Monitor for orthostatic hypotension, sedation, dry mouth, constipation, urinary retention 1, 3
• Check for cardiac effects (QTc prolongation, arrhythmias) 3

Titration Phase (Weeks 3-8):

• Continue dose escalation every 3-7 days if tolerated 1
• If inadequate response by 6-8 weeks, modify treatment 1
• Consider plasma level monitoring when approaching 100 mg/day 2

Maintenance Phase:

• Continue at lowest effective dose that maintains remission 2
• For depression: 4-9 months minimum after first episode 1
• For recurrent depression (≥2 episodes): consider indefinite maintenance 1

Advantages Over Other Tricyclics

Nortriptyline vs. Amitriptyline:

• Nortriptyline has fewer anticholinergic effects while maintaining equivalent efficacy 3
• Better tolerated, especially in elderly patients 3
• Less sedating than amitriptyline 1, 3
• Amitriptyline is metabolized to nortriptyline, making combination redundant 3

Common Pitfalls to Avoid

Dosing Errors:

• Do not exceed 150 mg/day without plasma level monitoring 2
• Do not combine with amitriptyline (nortriptyline is amitriptyline's active metabolite) 3
• Avoid starting at full doses in elderly patients 1, 2

Monitoring Failures:

• Do not wait beyond 6-8 weeks to modify inadequate treatment 1
• Do not discontinue prematurely (adequate trial requires 6-8 weeks) 1
• Clinical findings should predominate over plasma concentrations as primary determinants of dosage 2

Contraindications:

• Avoid in recent MI, arrhythmias, heart block 3
• Contraindicated in prolonged QTc syndrome 3
• Use caution with medications that prolong QTc or inhibit metabolism 3

Adverse Effect Management

Most Common Side Effects:

• Anticholinergic: dry mouth, constipation, urinary retention, blurred vision 3
• Cardiovascular: orthostatic hypotension, QTc prolongation 3
• CNS: sedation, confusion (especially in elderly) 3

Management Strategy:

• Reduce dose if minor side effects develop 2
• Discontinue promptly if serious adverse effects or allergic manifestations occur 2
• For constipation at higher plasma levels (80-120 ng/mL), consider dose reduction if tolerable 4