What is the recommended dosing regimen for nortriptyline (tricyclic antidepressant) in the treatment of major depressive disorder and chronic pain management?

Nortriptyline Dosing Recommendations

For neuropathic pain, start nortriptyline at 25 mg at bedtime and increase by 25 mg every 3-7 days as tolerated to a maximum of 150 mg/day, requiring 6-8 weeks with at least 2 weeks at maximum tolerated dose for an adequate trial. 1

Neuropathic Pain Management

Starting dose: Begin with 25 mg at bedtime 1

Titration schedule: Increase by 25 mg/day every 3-7 days as tolerated 1

Maximum dose: 150 mg/day; if blood concentration of active medication and its metabolite is <100 ng/mL, continue titration with caution 1

Duration of adequate trial: 6-8 weeks with at least 2 weeks at maximum tolerated dosage 1

Key advantage: Nortriptyline is preferred over tertiary-amine tricyclics (like amitriptyline) due to fewer anticholinergic effects while maintaining equivalent efficacy 1, 2, 3

Major Depressive Disorder

Starting dose: 25 mg 3-4 times daily for adults, or the total daily dose may be given once daily 4

Titration: Begin at a low level and increase gradually, checking clinical response and noting any intolerance 4

Therapeutic range: When doses exceed 100 mg daily, monitor plasma levels and maintain in the optimum range of 50-150 ng/mL 4

Maximum dose: Doses above 150 mg per day are not recommended 4

Duration of treatment: Continue for 4-9 months after first episode; patients with recurrent depression (2+ episodes) may benefit from prolonged treatment 1

Special Populations

Elderly Patients

Starting dose: 30-50 mg/day in divided doses, or 10-25 mg at bedtime 4, 3

Titration: Use substantially lower doses with slower titration every 3-7 days to minimize side effects 3

Rationale: Elderly patients are more sensitive to anticholinergic effects (dry mouth, orthostatic hypotension, confusion, urinary retention) and may have higher plasma concentrations of the active metabolite 10-hydroxynortriptyline 1, 3, 4

Preferred over amitriptyline: Nortriptyline has fewer anticholinergic effects, making it better tolerated in geriatric populations 1, 3

Outpatients vs Hospitalized Patients

Lower dosages are more important for outpatients than hospitalized patients who receive close supervision 4

Critical Monitoring Requirements

Cardiac Screening

ECG monitoring: Obtain screening electrocardiogram for patients older than 40 years before initiating therapy 1, 3

Cardiac precautions: Prescribe with caution in patients with ischemic cardiac disease or ventricular conduction abnormalities, limiting dosages to <100 mg/day when possible 1

Contraindications: Avoid in patients with recent MI, arrhythmias, heart block, or prolonged QTc syndrome 2, 3

Plasma Level Monitoring

Therapeutic window: Optimal responses occur with plasma concentrations of 50-150 ng/mL 4

When to monitor: Check plasma levels when doses exceed 100 mg daily 4

Higher concentrations: May be associated with more adverse experiences and cardiotoxicity, even within "therapeutic range" in elderly patients 4

Clinical priority: Clinical findings should predominate over plasma concentrations as primary determinants of dosage changes 4

Common Pitfalls and Caveats

Drug Interactions

Avoid combination with amitriptyline: Nortriptyline is the active metabolite of amitriptyline, making combination pharmacologically redundant and increasing risk of serotonin syndrome and cardiac toxicity 2, 3

SSRI combinations: Use caution when combining with SSRIs due to serotonin syndrome risk, particularly within 24-48 hours of dose increases; requires intensive monitoring during transitions 3

MAOI contraindication: Absolute contraindication due to severe interaction risk 3

Adverse Effects Management

Most common: Sedation, dry mouth, orthostatic hypotension, confusion, weight gain, urinary retention, constipation, blurred vision 2

Dose-dependent: Anticholinergic effects can be reduced by starting with lower dosages and titrating cautiously 1

If minor side effects develop: Reduce the dosage 4

If serious adverse effects occur: Discontinue promptly 4

Pain vs Depression Dosing

Pain relief often occurs at lower doses (25-100 mg/day) than required for depression treatment 3

For neuropathic pain, therapeutic benefit may be achieved before reaching maximum antidepressant doses 1

Treatment Response Timeline

Neuropathic pain: Requires 6-8 weeks for adequate trial, including at least 2 weeks at maximum tolerated dose 1

Depression: Monitor response within 6-8 weeks of initiation; modify treatment if inadequate response 1

Maintenance therapy: After satisfactory response, continue for 4-9 months for first episode; longer duration for recurrent depression 1