What is a recommended taper regimen for a patient taking dexedrine (dextroamphetamine) for Attention Deficit Hyperactivity Disorder (ADHD) and pregabalin, who needs to taper from a high dose of 1200mg to minimize withdrawal symptoms and maintain comfort during the day?

Pregabalin Taper Schedule with Concurrent Dexedrine Use

For a patient on 1200mg pregabalin daily who requires daytime comfort while using dexedrine for ADHD, divide the pregabalin into three daily doses (morning, midday, evening) and reduce by 10% of the current total daily dose per month, while maintaining stable dexedrine dosing throughout the taper. 1

Critical Safety Framework

• Never taper pregabalin rapidly from 1200mg—this dose is double the FDA-approved maximum of 600mg and indicates either severe dependence or off-label high-dose use. 2 Patients on doses exceeding 600mg daily have significantly higher rates of substance use disorders and require exceptionally cautious management. 2

• Maintain the dexedrine dose completely stable during the entire pregabalin taper—do not adjust stimulant medication while managing gabapentinoid withdrawal. 3, 4 The ADHD medication provides the foundation for daytime function and should not be modified to address withdrawal symptoms. 1

• Abrupt pregabalin discontinuation can cause severe withdrawal including anxiety, insomnia, nausea, sweating, and potentially seizures—the taper must be gradual. 3, 1

Recommended Daily Schedule

Current Baseline (1200mg pregabalin total daily)

• 7:00 AM: Dexedrine (patient's prescribed dose) + Pregabalin 400mg
• 12:00 PM: Dexedrine (if prescribed twice daily) + Pregabalin 400mg
• 8:00 PM: Pregabalin 400mg

This three-times-daily dosing maintains consistent pregabalin levels throughout the day given its 6.3-hour half-life, preventing the discomfort the patient experiences when doses are concentrated in the evening. 5 Steady state is achieved within 24-48 hours with pregabalin. 5

Month 1 Reduction (10% decrease to 1080mg total daily)

• 7:00 AM: Dexedrine + Pregabalin 360mg
• 12:00 PM: Dexedrine (if applicable) + Pregabalin 360mg
• 8:00 PM: Pregabalin 360mg

Month 2 Reduction (10% of current dose to 972mg total daily)

• 7:00 AM: Dexedrine + Pregabalin 324mg
• 12:00 PM: Dexedrine (if applicable) + Pregabalin 324mg
• 8:00 PM: Pregabalin 324mg

Month 3 Reduction (10% of current dose to 875mg total daily)

• 7:00 AM: Dexedrine + Pregabalin 292mg
• 12:00 PM: Dexedrine (if applicable) + Pregabalin 292mg
• 8:00 PM: Pregabalin 291mg

Continue this pattern of 10% monthly reductions of the current total daily dose, redistributed equally across the three daily doses. 1 Each reduction should be 90% of the previous dose to maintain consistent receptor occupancy changes. 6, 7

Timing Considerations with Dexedrine

• Administer morning pregabalin dose simultaneously with dexedrine to simplify the regimen and ensure the patient doesn't miss doses. 3 The presence of food does not affect pregabalin absorption, so timing around meals is not critical. 5

• The midday pregabalin dose should coincide with the second dexedrine dose if the patient takes stimulants twice daily. 3 If dexedrine is once-daily, the noon pregabalin dose stands alone.

• Space doses approximately 6-8 hours apart to maintain therapeutic levels and prevent withdrawal symptoms between doses. 5 The 6.3-hour half-life of pregabalin necessitates this frequency. 5

Managing Withdrawal Symptoms During Taper

• Monitor at least monthly with more frequent contact during difficult phases. 3, 1 Use phone contact or telehealth between visits to assess tolerance. 3

• For anxiety symptoms: Implement cognitive behavioral therapy rather than adding benzodiazepines, which create additional withdrawal risk. 3, 1, 6 CBT significantly increases taper success rates. 1

• For insomnia: Use sleep hygiene education first-line. 1 Consider trazodone 25-200mg for short-term management if non-pharmacologic approaches fail. 3, 6

• For nausea: Use antiemetics as needed. 6 Loperamide can address gastrointestinal discomfort but avoid high doses due to cardiac risks. 3

• For muscle aches: NSAIDs or acetaminophen are appropriate. 1

Critical Pitfalls to Avoid

• Never reduce by a fixed percentage of the original 1200mg dose—always calculate reductions as a percentage of the current dose. 1, 6 Straight-line reductions subject patients to disproportionately large decrements at the end of the taper. 1

• If withdrawal symptoms emerge, pause the taper at the current dose for 2-4 weeks before attempting further reduction. 3, 1 Clinically significant withdrawal signals the need to slow the taper rate. 3

• Never abandon the patient if tapering proves difficult—maintain the therapeutic relationship and consider slower reduction rates or temporary maintenance at a lower dose. 3, 6

• Do not add benzodiazepines to manage withdrawal anxiety, as this substitutes one dependence for another. 1 Use gabapentin as an alternative if additional GABAergic support is needed, though this also requires eventual tapering. 1, 8

Realistic Timeline and Expectations

• From 1200mg to 600mg (FDA maximum): Expect 6-7 months minimum. 1, 6

• From 600mg to discontinuation: Expect an additional 6-12 months. 1, 6 The case literature documents tapers from high-dose gabapentinoids requiring 18 months. 8

• Total expected duration: 12-18 months for complete discontinuation. 1, 6, 8 The goal is durability of the taper, not speed. 3, 1

• Once below 300mg total daily, consider slowing to 20-30mg monthly decrements. 8 For the final 100mg, reduce by 5-10mg every 1-2 weeks. 8

Monitoring Requirements

• Check blood pressure and pulse at each visit, as pregabalin withdrawal can cause autonomic symptoms. 1

• Screen for depression, anxiety, and substance use disorders that may emerge during tapering. 1

• Assess withdrawal symptoms explicitly: anxiety, insomnia, sweating, tremor, nausea, muscle aches, and irritability. 3, 1

• Document the patient's functional status and ability to maintain work, social activities, and self-care throughout the taper. 3

When to Refer to Specialist

• History of seizures or withdrawal seizures requires immediate specialist involvement. 1

• Co-occurring substance use disorders beyond the pregabalin dependence warrant addiction medicine consultation. 1

• Unstable psychiatric comorbidities necessitate psychiatric collaboration. 1

• Previous unsuccessful taper attempts indicate need for specialized support, potentially including intensive outpatient or partial hospitalization programs. 3, 1