What is the typical dosage of Nortriptyline (a tricyclic antidepressant) for treating depression?

Nortriptyline Dosing for Depression

For treating depression, nortriptyline should be started at 10-25 mg at bedtime and titrated gradually every 3-7 days to a target dose of 75-150 mg/day, with therapeutic drug monitoring targeting plasma levels of 50-150 ng/mL (optimal around 100 ng/mL). 1

Initial Dosing Strategy

• Start with 10-25 mg at bedtime to minimize side effects, particularly in elderly patients who are more sensitive to anticholinergic and sedative effects 1
• Increase by 25 mg increments every 3-7 days as tolerated 1
• The gradual titration approach over 2-4 weeks reduces adverse effects while reaching therapeutic levels 2

Target Therapeutic Dose and Plasma Levels

• The typical maintenance dose for depression is 75-150 mg/day, with most patients responding within this range 1
• Therapeutic plasma concentration should be maintained between 50-150 ng/mL, with an optimal target around 100 ng/mL 1, 3
• Research demonstrates that approximately 50-70% norepinephrine transporter (NET) occupancy occurs at doses of 75-200 mg/day, with the minimum therapeutic plasma level of 70 ng/mL corresponding to approximately 50% NET occupancy 4
• The ED₅₀ (dose required for 50% NET occupancy) is approximately 66 mg/day with a plasma concentration of 80 ng/mL 4

Therapeutic Drug Monitoring

• Check plasma levels during the second week of treatment to guide dose adjustments and ensure levels are within the therapeutic window 3
• Approximately 40% of patients initially require dose increases due to subtherapeutic plasma levels from cautious initial dosing 3
• Monitoring is particularly important in elderly patients, where a single 50 mg test dose can predict the maintenance dose needed to achieve steady-state concentrations of 50-150 ng/mL 5

Clinical Response Expectations

• An adequate trial requires 4-6 weeks, including time for titration 2
• Approximately 40% of patients with treatment-resistant depression respond to nortriptyline, with 12% achieving remission 6
• Therapeutic outcomes are equivalent or better in elderly patients (≥65 years) compared to younger patients when plasma levels are properly monitored 3

Important Safety Considerations

• Common adverse effects include sedation, dry mouth, orthostatic hypotension, confusion, urinary retention, constipation, and blurred vision, though nortriptyline has fewer anticholinergic effects than amitriptyline 1
• Both drugs are contraindicated in patients with recent MI, arrhythmias, heart block, or prolonged QTc syndrome 1
• Monitor for cardiac conduction abnormalities, particularly in patients with pre-existing cardiac disease 1
• Taper gradually over 10-14 days when discontinuing to avoid withdrawal syndrome 2

Special Population Considerations

• Elderly patients should start at the lower end of the dosing range (10-25 mg) due to increased sensitivity to anticholinergic and sedative effects 1, 5
• In elderly patients, mean daily doses of 50 mg (range 20-100 mg) often achieve therapeutic plasma concentrations 5
• Nortriptyline is preferred over amitriptyline in elderly patients due to its superior side effect profile 1