What is the recommended management for withdrawal in a patient with combined ketamine use disorder and alcohol use disorder?

Management of Combined Ketamine and Alcohol Use Disorder Withdrawal

Immediate Priority: Alcohol Withdrawal Management

Treat the alcohol withdrawal syndrome with standard benzodiazepine-based protocols and thiamine supplementation; ketamine use disorder does not require specific pharmacological withdrawal management and should not alter your approach to the life-threatening alcohol withdrawal. 1, 2

Critical First Steps

• Administer thiamine 100-500 mg IV immediately before any glucose-containing fluids to prevent precipitating acute Wernicke encephalopathy—this is mandatory in all alcohol-dependent patients regardless of concurrent ketamine use 1, 2

• Assess alcohol withdrawal severity using the CIWA-Ar scale: scores ≥8 indicate need for benzodiazepine treatment, scores ≥15 indicate severe withdrawal requiring aggressive management 1, 2

• Monitor vital signs continuously for autonomic instability (tachycardia, hypertension, fever, sweating) and evaluate for dangerous complications including dehydration, electrolyte imbalance (especially magnesium), infection, and hepatic encephalopathy 1, 2

Benzodiazepine Protocol for Alcohol Withdrawal

• Start diazepam 10 mg orally 3-4 times during the first 24 hours, then reduce to 5 mg 3-4 times daily as needed for patients without hepatic dysfunction 2

• Alternatively, initiate chlordiazepoxide 50-100 mg orally as loading dose, followed by 25-100 mg every 4-6 hours based on withdrawal severity, with maximum 300 mg in first 24 hours 1

• Switch to lorazepam 6-12 mg/day in patients with hepatic dysfunction, elderly patients, or when IV administration is needed, as it has safer metabolism and shorter half-life 1, 2

• Long-acting benzodiazepines like diazepam provide superior protection against seizures and delirium tremens compared to shorter-acting agents 1

• Do not continue benzodiazepines beyond 10-14 days due to abuse potential—this is especially critical given the dual substance use disorder 1

Ketamine Use Disorder Considerations

Ketamine withdrawal does not require specific pharmacological management. Unlike alcohol, abrupt ketamine cessation does not produce life-threatening withdrawal symptoms or require medication-assisted detoxification. 3, 4, 5

• The evidence on ketamine for treating alcohol use disorder is preliminary and mixed, with studies showing inconsistent results on relapse, craving, and withdrawal outcomes 3, 4

• Do not use ketamine as part of the withdrawal management protocol—while some research explores ketamine as a potential treatment for alcohol use disorder in combination with psychotherapy, this is investigational and not appropriate during acute withdrawal 3, 4, 5

• Focus on supportive care and psychiatric evaluation for the ketamine use disorder after alcohol withdrawal stabilization 3, 4

Essential Supportive Care

• Continue thiamine 100-300 mg/day orally for 2-3 months following resolution of withdrawal symptoms 1, 2

• Provide fluid and electrolyte replacement with careful attention to magnesium levels, which are commonly depleted in chronic alcohol use 1, 2

• Use symptom-triggered dosing rather than fixed-schedule benzodiazepine administration to prevent drug accumulation and optimize outcomes 2

Indications for Inpatient Management

Admit to hospital if the patient has: 1, 2

• Significant withdrawal symptoms (CIWA-Ar ≥8 with vomiting and tremor)
• History of withdrawal seizures or delirium tremens
• Co-occurring serious medical or psychiatric illness
• Failure of prior outpatient treatment
• High levels of recent drinking (>80 g/day for ≥10 years)
• Insufficient social support or inability to attend daily monitoring

Post-Acute Management Algorithm

• Psychiatric consultation is mandatory after stabilization for evaluation of both alcohol use disorder and ketamine use disorder, ongoing treatment planning, and long-term abstinence strategies 1, 2

• After withdrawal completion (typically 5-7 days), consider evidence-based relapse prevention medications for alcohol use disorder: 2

  • Acamprosate 1,998 mg/day for patients ≥60 kg, started 3-7 days after last alcohol consumption, continued 3-6 months
  • Naltrexone 25 mg for 1-3 days, then 50 mg daily for 3-12 months (avoid in liver disease due to hepatotoxicity risk)
  • Baclofen (not exceeding 80 mg/day) or topiramate as alternatives

• Coordinate care between addiction specialists and psychiatrists to address both substance use disorders simultaneously 2

• Encourage engagement with mutual help groups (Alcoholics Anonymous) and offer structured psychological interventions 2

Critical Pitfalls to Avoid

• Never administer glucose-containing IV fluids before thiamine—this can precipitate acute Wernicke encephalopathy 1, 2

• Do not use anticonvulsants for alcohol withdrawal seizures—these are rebound phenomena with lowered seizure threshold, not genuine seizures requiring anticonvulsant therapy 1, 2

• Avoid antipsychotics as monotherapy—they increase seizure risk and should only be used as adjunct to benzodiazepines in severe delirium unresponsive to adequate benzodiazepine doses 2

• Do not use naltrexone during acute withdrawal, especially in patients with liver disease 2

• Benzodiazepines are the only proven treatment to prevent seizures and reduce mortality from delirium tremens—no other agent should replace them as first-line therapy 1, 2