What is the recommended protocol for discontinuing nortriptyline (tricyclic antidepressant)?

Nortriptyline Discontinuation Protocol

Nortriptyline should be discontinued through gradual dose tapering over 10-14 days minimum, with dose reductions of approximately 25% every 5-7 days, to minimize withdrawal symptoms and prevent relapse. 1

Recommended Tapering Schedule

• Reduce the dose by 25% of the current dose every 5-7 days until complete discontinuation 1
• The minimum tapering period should be 10-14 days to limit withdrawal symptoms 1
• For patients at higher risk of withdrawal (see below), extend the taper to several weeks or months with smaller dose reductions 1

Example tapering regimen for a patient on 40 mg/day:

• Week 1: Reduce to 30 mg/day (25% reduction)
• Week 2: Reduce to 20 mg/day (33% reduction from 30 mg)
• Week 3: Reduce to 10 mg/day (50% reduction from 20 mg)
• Week 4: Discontinue 1

Risk Factors for Difficult Discontinuation

Patients with the following characteristics require slower, more gradual tapering 1:

• Previous withdrawal symptoms when missing doses or during prior discontinuation attempts
• Higher doses (above the minimum effective dose of 10 mg/day) 2
• Longer duration of treatment (more than 6 months)
• Older adults who are more sensitive to anticholinergic effects, orthostatic hypotension, and sedation 1

For these patients, consider tapering over several months with dose reductions smaller than 25% 3, 4

Withdrawal Symptoms to Monitor

Common withdrawal symptoms include: 5, 6

• Somatic symptoms: dizziness, light-headedness, nausea, fatigue, myalgia, flu-like symptoms, sensory disturbances, sleep disturbances
• Psychological symptoms: anxiety, agitation, crying spells, irritability
• Adrenergic hyperactivity: increased heart rate, sweating, tremor 1

Most withdrawal symptoms are mild and self-limiting, typically resolving within 1-2 weeks 5, 6

Critical Distinction: Withdrawal vs. Relapse

A major pitfall is confounding withdrawal symptoms with relapse of depression. 4 Withdrawal symptoms typically:

• Emerge within 1-5 days of dose reduction or discontinuation 5
• Are often physical (dizziness, nausea, flu-like symptoms) in addition to mood changes 5
• Improve rapidly (within days) if the medication is restarted 5

Relapse of depression typically:

• Develops more gradually over weeks 4
• Presents primarily with core depressive symptoms (anhedonia, hopelessness, guilt)
• Does not improve rapidly with medication reinitiation 4

Management of Withdrawal Symptoms

For mild symptoms: 5

• Reassure the patient that symptoms are usually transient and self-limiting
• Continue the current taper schedule with close monitoring

For moderate to severe symptoms: 5, 3

• Reinstitute the previous dose that was tolerated
• Wait until symptoms resolve (typically 5-7 days)
• Resume tapering at a slower rate (e.g., 10% dose reductions every 2-4 weeks instead of 25% every 5-7 days)
• Consider hyperbolic (exponential) tapering to very low doses (below 10 mg) before complete cessation 3

Monitoring Schedule

• Schedule follow-up visits at each dose reduction to assess for withdrawal symptoms and relapse 1

• Monitor specifically for: 1

  • Anticholinergic effects (dry mouth, constipation, urinary retention, confusion)
  • Orthostatic hypotension (measure blood pressure sitting and standing)
  • Cardiac effects (heart rate, rhythm abnormalities)
  • Mood and anxiety symptoms
  • Sleep disturbances

• Continue monitoring for several weeks after complete discontinuation to identify delayed relapse 1

Special Populations

Older adults (≥65 years): 1

• Use even more gradual tapering (e.g., 10% reductions every 2-4 weeks)
• Monitor closely for falls risk due to orthostatic hypotension and sedation
• Watch for cognitive impairment and delirium

Patients using nortriptyline for chronic pain: 1

• Implement concurrent pain management strategies during tapering
• Consider alternative analgesics before discontinuation
• Monitor pain levels at each dose reduction

When to Reassess Discontinuation

After 9 months of treatment, reassess the need for continued medication through dose reduction 1. However, patients with recurrent depression (two or more prior episodes) have higher relapse rates and may require longer-term or indefinite treatment 4.

Key Contraindications to Abrupt Discontinuation

Never abruptly discontinue nortriptyline except in cases of: 1

• Confirmed drug diversion
• Serious medical toxicity requiring immediate cessation
• Even in these situations, provide a safe tapering regimen or transition to alternative care 1

Abrupt discontinuation significantly increases risk of withdrawal symptoms and relapse 5, 4, 6