Table 1.

Exclusion criteria

(i) An alternate etiology for delirium thought to be more likely than alcohol withdrawal

(ii) Age <16 years

(iii) Pregnancy (positive assay for ßhCG—a urine assay or blood test will be performed for all women < 55 years)

(iv) Current breastfeeding

(v) Severe acute hepatitis (AST or ALT >500); liver failure (INR >2 not otherwise explained)

(vi) A presenting complaint of neurotrauma, brain mass, or intra-cranial bleed; abnormal cell count or gram stain on lumbar puncture (if performed)

(vii) A strong clinical suspicion of recent co-ingestion of depressant drugs (e.g., opioids, toxic alcohols, gamma-hydroxy-butyrate)

(viii) Hemodynamic instability (systolic blood pressure [SBP] < 90 mmHg)

(ix) History of barbiturate allergy

(x) History of porphyria

(xi) History of myasthenia gravis

(xii) Inability to obtain IV access

(xiii) Anticipated transfer to another center

(ivx) Stated intent to leave against medical advice

(xv) Active outpatient prescription for anti-retroviral therapy for HIV

(xvi) Active outpatient prescription for one of the following anti-epileptic drugs: valproic acid, phenytoin, carbamazepine, clobazam, lacosamide, lamotrigine, levetiracetam, topiramate, primidone, or phenobarbital

(xvii) Active outpatient prescription for an anticoagulant medication with a significant metabolic interaction with phenobarbital (i.e., warfarin or apixaban)

(xviii) Active outpatient prescription for a monoamine oxidase inhibitor (e.g., phenelzine, selegiline, tranylcypromine, isocarboxazid)

(ixx) Renal failure, as defined by a creatinine clearance <10 ml/min (as calculated by the Cockcroft-Gault equation) and/or active receipt of renal replacement therapy (dialysis)

(xx) Administration of IV or oral phenobarbital during the index admission prior to randomization.