What is the recommended dosage of nortriptyline (tricyclic antidepressant) for treating depression or neuropathic pain?

Nortriptyline Dosage for Depression and Neuropathic Pain

For neuropathic pain, nortriptyline should be started at 10-25 mg at bedtime and gradually increased to 50-150 mg daily, with optimal plasma concentrations maintained between 50-150 ng/mL. 1, 2

Dosing Recommendations

For Depression:

• Initial dose: 25 mg 3-4 times daily or as a single bedtime dose 1
• Maintenance dose: 50-150 mg/day
• Maximum dose: 150 mg/day (doses above this are not recommended) 1
• Elderly patients: Lower dosing of 30-50 mg/day in divided doses 1

For Neuropathic Pain:

• Initial dose: 10-25 mg at bedtime 2
• Titration: Increase by 25 mg every 3-7 days as tolerated 2
• Target dose: 50-150 mg daily 2
• Duration of adequate trial: 6-8 weeks with at least 2 weeks at maximum tolerated dosage 2

Pharmacokinetics and Monitoring

• Plasma level monitoring: Maintain plasma concentrations between 50-150 ng/mL for optimal response 1
• Higher concentrations: May be associated with more adverse effects, including cardiotoxicity 1
• Administration: Can be given once daily at bedtime to minimize daytime sedation 2, 3
• Bioavailability: Better than gabapentin (which has nonlinear pharmacokinetics) 4

Efficacy

• Tricyclic antidepressants like nortriptyline are first-line treatments for neuropathic pain 2, 4
• Secondary amine TCAs (nortriptyline, desipramine) are better tolerated than tertiary amines (amitriptyline, imipramine) though possibly slightly less efficacious 2
• Analgesic effects occur at lower doses than those required for antidepressant effects 2
• Onset of analgesic action is usually earlier than antidepressant effects 2

Adverse Effects and Precautions

• Common side effects: Anticholinergic effects (dry mouth, constipation, urinary retention), dizziness, sedation 2
• Cardiac considerations: Use with caution in patients with ischemic cardiac disease or ventricular conduction abnormalities 2
  • Obtain screening ECG for patients older than 40 years
  • Try to limit doses to less than 100 mg/day in patients with cardiac risk factors
• Elderly patients: Require lower doses due to increased sensitivity to adverse effects 1
• Renal impairment: Dose adjustment may be required 4

Treatment Algorithm

1. Initial Assessment:

   • Confirm diagnosis of neuropathic pain or depression
   • Screen for contraindications (cardiac disease, glaucoma, urinary retention)
   • Obtain baseline ECG for patients over 40 years

2. Initiation:

   • Start with 10-25 mg at bedtime for neuropathic pain
   • Start with 25 mg 3-4 times daily or once at bedtime for depression

3. Titration:

   • Increase by 25 mg every 3-7 days as tolerated
   • Monitor for side effects at each dose increase
   • Aim for total daily dose of 50-150 mg

4. Monitoring:

   • Assess efficacy after 6-8 weeks with at least 2 weeks at maximum tolerated dose
   • Consider plasma level monitoring to maintain 50-150 ng/mL
   • Monitor for adverse effects at each visit

5. Maintenance:

   • Continue effective dose for long-term management
   • Periodically reassess need for continued treatment
   • Consider gradual dose reduction if symptoms resolve

Important Considerations

• If partial response, consider adding another first-line agent (gabapentin, pregabalin) 2
• If no response after adequate trial, switch to alternative first-line medication 2
• Nortriptyline may be less effective for certain types of neuropathic pain (e.g., HIV-related neuropathies) 5
• Once-daily dosing may improve adherence and is equally effective to divided doses 3

Caution

• Avoid abrupt discontinuation; taper gradually to prevent withdrawal symptoms
• Monitor closely in patients with comorbid conditions (cardiac disease, prostatic hypertrophy, glaucoma)
• Consider drug interactions, particularly with other CNS depressants