What are the risks and recommended treatment for a patient who has taken high doses of pregabalin (Lyrica) recreationally for 5 consecutive evenings, with escalating doses ranging from 450mg to 1350mg, and is now seeking medical attention after stopping use?

Immediate Management of Acute Pregabalin Recreational Overdose and Withdrawal Risk

You must immediately assess for life-threatening complications from the 1350mg dose taken yesterday evening, provide supportive care, and implement a rapid taper protocol to prevent withdrawal seizures while monitoring for respiratory depression and cardiac complications. 1

Immediate Assessment and Stabilization (First 24-48 Hours)

Critical Vital Sign Monitoring

• Monitor for respiratory depression, reduced consciousness, and cardiac conduction abnormalities (heart block has been reported in pregabalin overdose), as these are the most dangerous acute complications 1
• Check oxygen saturation continuously for the first 24 hours, as serious breathing problems occur with high-dose pregabalin, particularly given the rapid bolus dosing pattern used 2
• Assess for confusional state, agitation, restlessness, depression/anxiety, and seizures—all reported signs of acute pregabalin overdose 1

Toxicological Considerations

• No specific antidote exists for pregabalin overdose—treatment is entirely supportive 1
• Gastric lavage is not indicated since the last dose was taken the previous evening (>12 hours ago) 1
• Hemodialysis removes approximately 50% of pregabalin in 4 hours and should be considered if the patient develops severe CNS depression, respiratory failure, or cardiac conduction abnormalities 1
• Contact Poison Control immediately for real-time guidance on managing this specific overdose scenario 1

Understanding the Abuse Pattern and Risks

Dose Escalation Analysis

• This patient escalated from 450mg to 1350mg over just 5 days—a 200% increase that demonstrates rapid tolerance development and high-risk abuse behavior 3, 4
• The 1350mg dose is 2.25 times the maximum therapeutic dose of 600mg/day, placing this patient in the very high abuse category 5, 6, 4
• Forensic studies show median serum concentrations in recreational users of 6.2 mg/L (range 0.68-111.6 mg/L), with nearly 50% exceeding therapeutic range 3
• The bolus dosing pattern (80% taken at once) creates dangerously high peak serum levels that maximize euphoric effects but also toxicity risk 3

Withdrawal Risk Assessment

• Abrupt discontinuation after 5 days of escalating high-dose use creates significant withdrawal risk, including seizures, auditory hallucinations, suicidal ideation, palpitations, tremors, irritability, and insomnia 7, 8, 9
• Withdrawal symptoms typically emerge within 24-48 hours of last dose and can persist for weeks without proper management 8, 9
• Never abruptly discontinue pregabalin—gradual taper over minimum 1 week is mandatory even after short-term use 5

Recommended Taper Protocol

Rapid Taper Schedule (Given Short Duration of Use)

Since exposure was only 5 days, a more aggressive taper is appropriate than for chronic users:

Days 1-2 (Current):

• Start pregabalin 300mg twice daily (600mg/day total) in divided doses 5
• This represents 44% of the peak dose and prevents severe withdrawal while beginning dose reduction 5

Days 3-4:

• Reduce to pregabalin 150mg twice daily (300mg/day total) 5
• Monitor closely for withdrawal symptoms (tremor, anxiety, insomnia, palpitations) 8

Days 5-6:

• Reduce to pregabalin 75mg twice daily (150mg/day total) 5

Days 7-8:

• Reduce to pregabalin 75mg once daily at bedtime 5

Day 9:

• Discontinue completely 5

If withdrawal symptoms emerge at any step, hold at that dose for 2-3 additional days before proceeding 5

Alternative Slower Taper (If Withdrawal Symptoms Develop)

• Extend each dose reduction step to 3-5 days instead of 2 days 5
• Consider adding adjunctive medications (see below) to manage specific withdrawal symptoms 8

Adjunctive Symptom Management

For Anxiety and Agitation

• Short-term benzodiazepines (lorazepam 0.5-1mg every 6-8 hours as needed) can manage acute anxiety and reduce seizure risk during taper 8
• Limit benzodiazepine use to 7-10 days maximum to avoid substituting one dependence for another 8

For Insomnia

• Consider mirtazapine 15-30mg at bedtime, which is safe and provides sedation without abuse potential 2
• Avoid additional gabapentinoids or Z-drugs due to cross-tolerance and abuse risk 2

For Psychotic Symptoms (If They Emerge)

• Low-dose antipsychotics (quetiapine 25-50mg or olanzapine 2.5-5mg) can manage hallucinations or severe agitation if they develop 8
• Auditory hallucinations and suicidal ideation have been reported in pregabalin withdrawal and typically resolve within 2 weeks 7, 8

Critical Monitoring Parameters

Daily Assessment During Taper

• Vital signs (BP, HR, temperature) twice daily 1
• Mental status examination for confusion, hallucinations, suicidal ideation 7, 8
• Withdrawal symptom severity using standardized scale 8
• Sleep quality and duration 8

Red Flags Requiring Emergency Evaluation

• Seizure activity (requires immediate hospitalization and IV benzodiazepines) 1, 9
• Suicidal ideation or plan (requires psychiatric emergency evaluation) 7, 8
• Severe confusion or altered consciousness (may indicate ongoing toxicity or complicated withdrawal) 1
• Cardiac arrhythmias or chest pain (heart block reported in overdose) 1

Addressing Underlying Addiction

Substance Use Disorder Evaluation

• This 5-day pattern of escalating recreational use meets criteria for substance use disorder (tolerance development, inability to control use, continued use despite harm) 8, 9
• Comprehensive substance use history is essential—recreational pregabalin users typically use it as part of a polydrug pattern (mean of 4 concomitant drugs in forensic studies) 3
• Screen for concurrent use of opioids, benzodiazepines, alcohol, or other CNS depressants 3, 4

Psychiatric Comorbidity Assessment

• Evaluate for underlying anxiety, depression, or chronic pain that may have motivated initial use 8, 9
• Some patients with no prior substance abuse history develop pregabalin dependence, suggesting vulnerability factors 9

Long-Term Treatment Plan

• Refer to addiction medicine or psychiatry for ongoing management after acute taper is complete 8, 9
• Consider cognitive behavioral therapy focused on substance use 8
• Address any underlying psychiatric conditions with appropriate non-addictive medications 8
• Implement strict prescription controls—pregabalin should not be prescribed to this patient in the future given demonstrated abuse pattern 8, 9

Common Pitfalls to Avoid

Do Not:

• Abruptly discontinue pregabalin even after short-term abuse—seizure risk is real 5, 9
• Underestimate withdrawal severity—patients have required hospitalization for pregabalin withdrawal after similar use patterns 7, 9
• Prescribe additional gabapentinoids (gabapentin) as substitution therapy—this simply transfers dependence 9
• Assume the patient will be honest about concurrent substance use—obtain urine drug screen 3
• Discharge without addiction medicine follow-up—relapse risk is extremely high without structured support 8, 9

Do:

• Document the abuse pattern clearly in the medical record to prevent future inappropriate prescribing 8, 9
• Educate the patient about the serious risks of pregabalin abuse, including death in combination with other CNS depressants 1, 9
• Provide written taper schedule with clear instructions and emergency contact information 5
• Schedule close follow-up (every 2-3 days during taper, then weekly for 4 weeks) 8

Prognosis and Expected Course

• Withdrawal symptoms should resolve within 48 hours to 2 weeks with appropriate taper and supportive care 7, 8
• Physical dependence after only 5 days is concerning and suggests high vulnerability to addiction 8, 9
• Long-term recovery requires addressing underlying psychiatric issues and addiction treatment—medical detoxification alone has high relapse rates 8, 9