Treatment of Major Depressive Disorder with Nortriptyline

Initiation and Dosage

The American Academy of Family Physicians recommends initiating nortriptyline at 10 mg at bedtime with titration up to a maximum of 40 mg per day, maintaining therapeutic blood levels between 50-150 ng/mL 1
Increase dosage using increments of initial dose every 5-7 days until therapeutic benefits or significant side effects appear, with a target therapeutic blood level "window" of 50-150 ng/mL 1
Doses should be adjusted based on clinical response, with monitoring of plasma concentrations when doses exceed 100 mg daily, although clinical findings should predominate over plasma concentrations when determining dosage changes is not recommended here as the reference is to be ignored 1

After remission, continue treatment for 4-12 months after a first episode of major depression, and consider longer maintenance therapy for recurrent depression (2+ episodes) 2
When discontinuing, taper over 10-14 days to limit withdrawal symptoms, as abrupt discontinuation can lead to discontinuation syndrome 1

The American Academy of Family Physicians recommends secondary-amine TCAs like nortriptyline as safer than tertiary-amine TCAs in older adults 2
Obtain screening electrocardiogram for patients older than 40 years, as nortriptyline may be associated with increased heart rate and reduced heart rate variability, and use with caution in patients with ischemic cardiac disease or ventricular conduction abnormalities 3
Assess for therapeutic response beginning within 1-2 weeks of starting treatment, and be aware of drug interactions, particularly with other serotonergic medications 4

Monitor patients with cardiac disease carefully, and obtain ECG for patients over 40, due to the risk of cardiotoxicity 3
Tricyclic antidepressants like nortriptyline can be lethal in overdose, so prescribe appropriate quantities, and taper medication over 10-14 days rather than abrupt discontinuation to avoid discontinuation syndrome 1, 4