What is the recommended dosing range for nortriptyline (tricyclic antidepressant) in the treatment of depression?

Nortriptyline Dosing for Depression

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

Standard Adult Dosing

• Initial dose: 25 mg three to four times daily, starting at the low end and increasing gradually based on clinical response and tolerability 1
• Maintenance range: 75-150 mg/day is the typical therapeutic dose range 2
• Maximum dose: 150 mg/day is the recommended ceiling; doses above this are not recommended due to increased adverse effects without additional benefit 1
• Alternative regimen: The total daily dose may be administered once daily at bedtime, which offers administrative advantages and is not inferior to divided dosing 2, 3

Therapeutic Drug Monitoring

Plasma level monitoring is strongly recommended (Level 1 recommendation) for nortriptyline, as it has an established therapeutic window. 2

• Target plasma concentration: 50-150 ng/mL (190-570 nmol/L) 2
• Optimal response: Plasma concentrations around 100 ng/mL are associated with best outcomes 4
• Above therapeutic window: Concentrations above 150 ng/mL are associated with decreased efficacy and increased adverse effects 2, 5
• Monitoring timing: Check plasma levels when doses exceed 100 mg/day to ensure they remain in the optimal range 1

Elderly Patients

• Reduced dosing: 30-50 mg/day in divided doses 1
• Maximum for elderly: 40 mg/day (given twice daily) 2
• Important consideration: Elderly patients may have higher plasma concentrations of the active metabolite 10-hydroxy-nortriptyline, which has been associated with cardiotoxicity even when parent drug levels are therapeutic 1

Dose Titration Strategy

• Titration schedule: Increase dosage using increments of the initial dose every 5-7 days until therapeutic benefits appear or significant side effects develop 2
• Clinical monitoring: Assess therapeutic response, adverse effects, and suicidal ideation within 1-2 weeks of starting therapy 6
• Response timeline: A full therapeutic trial requires at least 4-8 weeks 2
• Aggressive approach: Some evidence suggests starting with 75-125 mg based on weight may achieve therapeutic levels faster (81% reached therapeutic levels within 1 week), though this requires careful monitoring for orthostatic hypotension 7

Clinical Characteristics

• Sedating profile: Nortriptyline tends to be more sedating than desipramine, making it particularly useful in patients with agitated depression and insomnia 2
• Side effect profile: Similar tolerance profile to desipramine with lower risk for cardiotoxic, hypotensive, and anticholinergic effects compared to tertiary amine tricyclics 2
• Timing: Typically given at bedtime when used as a single daily dose due to sedating properties 2

Common Pitfalls to Avoid

• Underdosing: Approximately 40% of patients may have subtherapeutic plasma levels with conservative dosing, requiring dose increases 4
• Exceeding therapeutic window: Doses above 150 mg/day or plasma levels above 150 ng/mL reduce efficacy and increase side effects 1, 5
• Ignoring plasma levels: Clinical findings should predominate, but plasma monitoring helps optimize dosing, especially in elderly patients or those with inadequate response 1, 4
• Abrupt discontinuation: Taper over 10-14 days to limit withdrawal symptoms 2

Maintenance Treatment

• Duration after first episode: Continue for 4-9 months after satisfactory response 2, 6
• Recurrent depression: Patients with 2 or more episodes may require years to lifetime treatment 6
• Maintenance dosing: Use the lowest dose that maintains remission 1