Can a patient with alcohol withdrawal take Benadryl (diphenhydramine)?

Diphenhydramine (Benadryl) Should Generally Be Avoided in Patients with Alcohol Withdrawal

Diphenhydramine is not recommended for patients admitted with alcohol withdrawal because it can worsen confusion, increase the risk of delirium, and lacks efficacy in treating withdrawal symptoms—benzodiazepines remain the only proven first-line treatment.

Why Diphenhydramine Is Problematic in Alcohol Withdrawal

Risk of Worsening Delirium and Confusion

• Diphenhydramine has strong anticholinergic properties that can precipitate or worsen delirium in patients already at high risk for delirium tremens, which typically begins 48-72 hours after cessation and peaks at days 3-5 1
• Patients with alcohol withdrawal are particularly vulnerable to confusional states, and anticholinergic medications can obscure the clinical picture and make assessment more difficult 2
• The CIWA-Ar scoring system, which guides treatment intensity, relies on accurate assessment of mental status—anticholinergic effects can confound this assessment 3

Lack of Therapeutic Benefit

• Benzodiazepines are the only proven treatment to prevent seizures and reduce mortality from delirium tremens 1
• Diphenhydramine has no role in preventing the dangerous complications of alcohol withdrawal, including seizures and autonomic instability 3
• There is no evidence supporting antihistamines as adjunctive therapy in alcohol withdrawal management 4

What Should Be Used Instead

First-Line Treatment: Benzodiazepines

• Long-acting benzodiazepines (chlordiazepoxide or diazepam) provide superior protection against seizures and delirium tremens through gradual self-tapering 3
• For patients with hepatic dysfunction, switch to lorazepam 6-12 mg/day or oxazepam, which have shorter half-lives and safer metabolic profiles 1, 3
• Use symptom-triggered dosing guided by CIWA-Ar scores (>8 requires intervention, ≥15 requires aggressive treatment) to prevent drug accumulation while ensuring adequate symptom control 3

Mandatory Adjunctive Therapy

• Thiamine 100-300 mg/day orally must be given to every patient, or 100-500 mg IV for high-risk patients or suspected Wernicke encephalopathy 1, 3
• Thiamine must be administered BEFORE any glucose-containing IV fluids to prevent precipitating acute Wernicke encephalopathy 1

Common Clinical Scenarios Where Benadryl Might Be Requested

For Sleep Disturbance

• If insomnia is the concern, optimize benzodiazepine dosing rather than adding anticholinergic agents 3
• Ensure the patient is receiving adequate symptom-triggered benzodiazepines, as untreated withdrawal symptoms are often the cause of sleep disturbance 1

For Anxiety or Agitation

• Anxiety and agitation are core withdrawal symptoms that should be treated with benzodiazepines, not antihistamines 1
• Assess vital signs for autonomic instability (tachycardia, hypertension, fever) which indicate need for increased benzodiazepine dosing 1

For Nausea

• Address nausea with appropriate antiemetics (ondansetron, metoclopramide) rather than diphenhydramine 1
• Evaluate for complications such as pancreatitis, gastrointestinal bleeding, or hepatic encephalopathy that may be causing nausea 1

Critical Monitoring Considerations

• Monitor vital signs and withdrawal symptoms frequently, especially during the first 72 hours when symptoms peak 3
• Verify stable vital signs with no tachycardia, hypertension, or fever for at least 24 hours before considering any medication changes 5
• Screen for psychiatric comorbidities that may require specialized follow-up care, as psychiatric consultation is mandatory after stabilization 5, 1

Key Pitfall to Avoid

Do not add sedating medications like diphenhydramine to "help with sleep" or "calm the patient down"—this approach can mask withdrawal symptoms, worsen delirium, and delay appropriate escalation of benzodiazepine therapy, potentially leading to preventable complications including seizures and delirium tremens 1, 3.