What is the maximum recommended dose of nortriptyline (a tricyclic antidepressant) per day?

Maximum Dose of Nortriptyline

The maximum recommended dose of nortriptyline is 150 mg per day, with doses above this threshold not recommended due to lack of additional efficacy and increased risk of adverse effects, particularly cardiac toxicity. 1

FDA-Approved Dosing Guidelines

The FDA label provides clear dosing parameters 1:

• Standard adult dosing: 25 mg 3-4 times daily (75-100 mg/day total), starting at low doses and titrating upward based on clinical response
• Alternative once-daily regimen: Total daily dose may be given as a single dose
• Maximum dose: 150 mg per day - doses above this are explicitly not recommended 1
• Therapeutic plasma monitoring: When doses exceed 100 mg daily, plasma levels should be monitored and maintained in the optimal range of 50-150 ng/mL 1

Critical Safety Threshold

A large retrospective study demonstrated increased risk of sudden cardiac death with tricyclic antidepressant doses exceeding 100 mg/day, particularly in patients with cardiovascular disease or elderly patients. 2 This finding reinforces the importance of:

• Obtaining an electrocardiogram before initiating therapy, especially if doses will exceed 100 mg/day 2
• Avoiding these medications entirely if PR or QTc interval prolongation is present 2
• Using extreme caution in any patient with cardiovascular history 2

Special Population Dosing

Elderly patients require substantially lower doses 1:

• Recommended range: 30-50 mg/day in divided doses 1
• Start at 10 mg/day and titrate slowly 2
• Higher plasma concentrations of the active metabolite 10-hydroxynortriptyline occur in elderly patients, which has been associated with cardiotoxicity even when parent compound levels are within therapeutic range 1

Dosing for Neuropathic Pain

For painful diabetic peripheral neuropathy, the dosing strategy differs from depression treatment 2:

• Start at 10 mg/day, particularly in older patients 2
• Titrate gradually as needed up to 75 mg/day 2
• This is lower than the depression treatment maximum, as neuropathic pain often responds to lower doses

Pharmacokinetic Considerations

Individual dose requirements vary by a factor of 20 between patients 3, making therapeutic drug monitoring valuable:

• The average dose required to achieve a plasma level of 100 ng/mL is approximately 80 mg/day, but individual variation is substantial 3
• A 25 mg test dose with 24-hour plasma level measurement can predict steady-state requirements and identify slow metabolizers early 3
• Plasma levels are linear with daily dose, with a mean parameter of 1.21 ng/mL per mg/day 3

Common Pitfalls to Avoid

• Do not exceed 150 mg/day - there is no evidence of additional benefit and clear evidence of increased harm 1
• Do not combine with amitriptyline - nortriptyline is amitriptyline's active metabolite, making combination redundant and increasing toxicity risk 4
• Do not ignore cardiovascular screening - ECG monitoring is essential, particularly when approaching or exceeding 100 mg/day 2
• Do not use fixed dosing in elderly patients - they require individualized, lower doses with careful titration 1