What is the recommended dosage and treatment protocol for Nortriptyline (tricyclic antidepressant) for depression and chronic pain?

Nortriptyline Dosage and Treatment Protocol for Depression and Chronic Pain

For depression, nortriptyline should be started at 25 mg at bedtime and increased by 25 mg every 3-7 days as tolerated, up to a maximum of 150 mg/day. For neuropathic pain, start with 10-25 mg at bedtime and increase to 50-150 mg nightly, with an adequate trial requiring 6-8 weeks. 1, 2

Dosing for Depression

• Start with 25 mg orally at bedtime 2
• Titrate by increasing 25 mg every 3-7 days as tolerated 1
• Maximum recommended dose is 150 mg/day 2
• Alternative regimen: total daily dose may be given once daily 2
• Plasma levels should be maintained in the therapeutic range of 50-150 ng/mL when doses exceed 100 mg daily 2
• For elderly patients, use lower doses (30-50 mg/day in divided doses) 2
• An adequate trial requires 4-8 weeks, with at least 2 weeks at maximum tolerated dosage 1

Dosing for Neuropathic Pain

• Start with lower doses than for depression: 10-25 mg at bedtime 1
• Gradually increase every 3-5 days as tolerated 1
• Target dose range: 50-150 mg nightly 1
• Secondary amine TCAs like nortriptyline are preferred over tertiary amines (amitriptyline) due to better tolerability 1
• An adequate trial for pain requires 6-8 weeks with at least 2 weeks at maximum tolerated dosage 1
• Analgesic effects often occur at lower doses than those required for antidepressant effects 1, 3

Monitoring and Safety Considerations

• Monitor plasma concentrations when doses exceed 100 mg daily 2
• Obtain screening electrocardiogram for patients older than 40 years 1
• Use with caution in patients with cardiac disease; limit doses to less than 100 mg/day when possible 1
• Higher concentrations of nortriptyline (>150 ng/mL) may be associated with more adverse experiences 2
• Older patients may have higher plasma concentrations of the active metabolite 10-hydroxy nortriptyline, which has been associated with cardiotoxicity 2
• Clinical findings should predominate over plasma concentrations when determining dosage changes 2

Efficacy Considerations

• Nortriptyline is effective for approximately 40% of patients with treatment-resistant depression 4
• For neuropathic pain, nortriptyline is considered a first-line treatment option along with other secondary amine TCAs 1
• Nortriptyline tends to be more sedating than desipramine, making it useful for patients with agitated depression and insomnia 1
• The analgesic effect of nortriptyline is independent of its antidepressant effect 1, 5
• Efficacy for pain appears similar to gabapentin, though evidence quality is very low 6

Common Side Effects and Management

• Anticholinergic effects (dry mouth, constipation, urinary retention) are common but less severe than with tertiary amine TCAs 1
• Orthostatic hypotension may occur, particularly with higher initial doses 7
• Sedation is common and can be beneficial for patients with insomnia 1
• Side effects can be minimized by starting with low doses and titrating slowly 1
• When discontinuing, taper over 10-14 days to limit withdrawal symptoms 1

Treatment Duration

• For depression, after 9 months of treatment, consider dose reduction to reassess the need for continued medication 1
• For chronic pain, especially neuropathic pain, longer-term treatment is often required 1
• Regular reassessment of pain and health-related quality of life is recommended 1

Special Considerations

• Nortriptyline is not recommended for pediatric patients 2
• In patients with both depression and chronic pain, nortriptyline can address both conditions simultaneously 5
• For cancer-related neuropathic pain, nortriptyline can be used as a coanalgesic in combination with opioids 1
• In HIV-associated neuropathic pain, gabapentin is preferred as first-line treatment, with tricyclic antidepressants as second-line options 1