In a patient taking duloxetine (Cymbalta) 120 mg and amitriptyline 150 mg, should the amitriptyline be tapered rather than stopped abruptly?

Amitriptyline Must Be Tapered Gradually, Not Stopped Abruptly

In a patient taking duloxetine 120 mg and amitriptyline 150 mg, the amitriptyline must be tapered gradually over 4-8 weeks rather than stopped suddenly to prevent withdrawal symptoms and anticholinergic rebound. 1, 2

Why Gradual Tapering Is Essential

Abrupt discontinuation of tricyclic antidepressants like amitriptyline causes a well-documented anticholinergic discontinuation syndrome characterized by:

• Cholinergic rebound with nausea, sweating, and urinary urgency 1
• Irritability, dream disturbances, sleep disruption, and restlessness within the first 2 weeks 3
• Anxiety, agitation, and crying spells 2
• Dizziness, fatigue, and flu-like symptoms 2

These symptoms emerge because chronic anticholinergic drug use leads to compensatory upregulation of cholinergic receptors, and sudden removal causes unopposed cholinergic activity 1.

Recommended Tapering Protocol for Amitriptyline 150 mg

Reduce the dose by 25% of the original dose every 1-2 weeks:

• Weeks 1-2: Decrease to 112.5 mg daily (25% reduction) 4, 5
• Weeks 3-4: Decrease to 75 mg daily (another 25% reduction) 4
• Weeks 5-6: Decrease to 37.5 mg daily (another 25% reduction) 4
• Weeks 7-8: Decrease to 18.75 mg daily, then discontinue 4

This 6-8 week minimum timeline aligns with consensus recommendations for tapering psychotropic medications 6, 7.

Critical Monitoring During the Taper

Assess weekly for:

• Withdrawal symptoms (nausea, sweating, urinary urgency, irritability, sleep disturbances) 1, 3
• Mood symptoms and anxiety levels 6
• Pain levels, since amitriptyline may have been providing analgesic benefit 4

If severe withdrawal symptoms develop at any reduction step, return to the previous dose and extend each reduction phase by 1-2 weeks 6, 8.

Special Consideration: Duloxetine Interaction

Since this patient is on duloxetine 120 mg (which is above the typical maximum of 60-120 mg), the duloxetine should remain stable during the amitriptyline taper 4. When tapering benzodiazepines and opioids concurrently, guidelines recommend tapering opioids first due to greater risks of benzodiazepine withdrawal 4. Similarly, taper the amitriptyline first while maintaining stable duloxetine to avoid compounding withdrawal effects.

Duloxetine itself requires slow tapering when discontinued to prevent withdrawal symptoms 4, but that is not the current question.

Common Pitfalls to Avoid

• Never stop amitriptyline abruptly at this dose (150 mg), as withdrawal symptoms will be severe and distressing 1, 2, 3
• Do not mistake withdrawal symptoms for depression relapse - withdrawal typically occurs within 2 weeks of discontinuation, while relapse takes longer 2, 3
• Do not rush the taper below 4 weeks - faster tapers show minimal benefit over abrupt discontinuation and are poorly tolerated 9
• Do not abandon the patient during tapering - close monitoring and support are essential 4

Alternative Approach If Standard Taper Fails

If the patient cannot tolerate the 25% every 1-2 weeks reduction, consider:

• Slower hyperbolic tapering with exponential dose reductions extending to 3-4 months 9, 5
• Smaller dose reductions (10-15% every 2-3 weeks) for the final doses below 50 mg 9