What is the recommended protocol for stopping Cymbalta (duloxetine) and starting Pristiq (desvenlafaxine)?

Protocol for Stopping Duloxetine (Cymbalta) and Starting Desvenlafaxine (Pristiq)

When switching from duloxetine to desvenlafaxine, a gradual taper of duloxetine followed by initiation of desvenlafaxine is recommended to minimize discontinuation symptoms and ensure therapeutic efficacy.

Duloxetine Discontinuation Process

• Duloxetine should be tapered when discontinuing to prevent withdrawal symptoms, especially after treatment longer than 3 weeks 1
• Gradually reduce the dosage rather than stopping duloxetine abruptly whenever possible 2
• For patients on standard doses (60-120mg/day), consider the following tapering schedule:
  • Reduce by approximately 25% of the most recent dose every 1-2 weeks 3, 4
  • For example: 60mg → 45mg → 30mg → 20mg → 10mg → discontinue
• Slower tapering (over months) may be necessary for patients who have been on duloxetine long-term or who have experienced discontinuation symptoms previously 5

Common Duloxetine Discontinuation Symptoms

• Most common symptoms include dizziness (12.4%), nausea (5.9%), headache (5.3%), paresthesia (2.9%), vomiting (2.4%), irritability (2.4%), and nightmares (2.0%) 2
• Discontinuation symptoms typically begin within 1-3 days after dose reduction or discontinuation 2
• Most symptoms resolve within 7 days, though some may persist longer 2
• If severe discontinuation symptoms occur, reinstate the previous dose and resume tapering at a slower rate 5

Starting Desvenlafaxine Protocol

• The recommended starting dose for desvenlafaxine is 50 mg once daily, which is both a starting dose and the therapeutic dose 6
• Desvenlafaxine should be taken at approximately the same time each day with or without food 6
• Tablets must be swallowed whole with fluid and not divided, crushed, chewed, or dissolved 6
• Consider starting desvenlafaxine when duloxetine has been tapered to its lowest dose (10-20mg) or within 1-2 days after complete discontinuation of duloxetine 6, 7

Special Considerations

• For patients with moderate renal impairment (CrCl 30-50 mL/min), the maximum recommended dose of desvenlafaxine is 50 mg per day 6
• For patients with severe renal impairment (CrCl 15-29 mL/min), the maximum recommended dose is 25 mg every day or 50 mg every other day 6
• For patients with moderate to severe hepatic impairment (Child-Pugh score 7-15), the recommended dose is 50 mg per day 6
• Monitor patients closely during the transition period for emergence of discontinuation symptoms or changes in mood, anxiety, or suicidal ideation 1, 4

Management of Transition Complications

• If discontinuation symptoms emerge during the transition, options include:
  • Slowing the taper of duloxetine further 4
  • Temporarily increasing the duloxetine dose back to the previous level before attempting a more gradual taper 5
  • Symptomatic management of specific discontinuation symptoms (e.g., antiemetics for nausea) 4
• If symptoms persist despite these measures, consider consulting with a psychiatrist or pain specialist 7

Follow-up and Monitoring

• Reassess pain and health-related quality of life frequently during and after the transition 7
• Continue treatment with desvenlafaxine if substantial pain relief (average pain reduced to ≤3/10) and tolerable side effects are achieved 7
• If desvenlafaxine provides inadequate relief, consider other first-line medications for neuropathic pain such as gabapentin, pregabalin, or tricyclic antidepressants 7

This protocol balances the need to minimize discontinuation symptoms while ensuring continued therapeutic effect for the patient's underlying condition, whether it be neuropathic pain, depression, or anxiety.