Table 1.

Non-benzodiazepine anticonvulsants for alcohol withdrawal syndrome

Drug	Sample(s)	Study design(s)	Intervention dosing and duration	Outcome measures	Level of evidencea
Carbamazepine	Inpatient, outpatient, severe AWS	SR Randomized double-blind comparison with benzodiazepines Randomized, double-blind, placebo-controlled study Randomized, open-label pilot study comparison with benzodiazepines and tiapride	Carbamazepine fixed dose starting at 800 mg/day tapered over 4, 7, 9, or 12 days; symptom-triggered dosing (≤1200 mg/day)	Reduction in observer-rated AWS symptoms, episodes of AW seizures, AW delirium (DT), treatment dropout	Grade B (level 2 evidence) for AWS
Oxcarbazepine	Inpatient, severe AWS	Randomized, single-blind pilot study comparison with carbamazepine Randomized, double-blind, placebo-controlled adjunct to benzodiazepines	Oxcarbazepine fixed dose starting at 900 mg/day and tapered over 5-6 days	Amount of symptom-triggered benzodiazepine for safe detoxification, reduction in observer-rated AWS symptoms, AW seizures, AW delirium	Grade C (level 3 evidence) for AWS
Valproic acid/divalproex	Inpatient	SR Randomized, double-blind, placebo-controlled study	Divalproex sodium 500 mg 3 times per day	Amount of symptom-triggered benzodiazepine for safe detoxification, reduction in observer-rated AWS symptoms, AW seizures, AW delirium	Grade B (level 2 evidence) for AWS
Gabapentin	Inpatient, outpatient, moderate AWS, severe AWS	Open-label pilot study Randomized, placebo-controlled adjunct to benzodiazepines Randomized, open-label comparison with phenobarbital with benzodiazepines Randomized, double-blind comparison with benzodiazepines (lorazepam and chlordiazepoxide) Open-label gabapentin dose challenge followed by stratification to gabapentin or benzodiazepines based upon initial response	Gabapentin fixed-taper dosing (starting dose ranging from 600 to 1600 mg/day)	Amount of symptom-triggered benzodiazepine for safe detoxification, reduction in observer-rated AWS symptoms	Grade B (level 2 evidence) for AWS
Pregabalin	Inpatient, outpatient, mild-to-moderate AWS	Open-label study Randomized comparison with tiapride and lorazepam Randomized, double-blind, placebo-controlled trial	Pregabalin flexible dosing between 200 and 450 mg/day	Amount of symptom-triggered benzodiazepine for safe detoxification, reduction in observer-rated AWS symptoms	Grade C (level 3 evidence) for AWS
Levetiracetam	Inpatient	Randomized, double-blind, placebo-controlled adjunct to benzodiazepines	Levetiracetam fixed dose starting at 2000 mg/day tapered over 6 days	Amount of symptom-triggered benzodiazepine for safe detoxification (primary), reduction in AWS symptoms (secondary)	Grade C (level 3 evidence) for AWS
Topiramate	Inpatient, male	Randomized, single-blind, placebo-controlled comparison with benzodiazepines (diazepam), lamotrigine, and memantine with symptom-triggered rescue benzodiazepine [46] Open-label pilot studies	Topiramate 25 mg fixed dose every 6 h (100 mg/day) over 7 days	Reduction in observer-rated and self-reported AWS symptoms, severity and episodes of AW seizures	Grade C (level 3 evidence) for AWS
Zonisamide	Combined inpatient (2 weeks) and outpatient (1 week)	Randomized, open-label pilot study comparison with benzodiazepines (diazepam) with symptom-triggered rescue benzodiazepines	Zonisamide flexible dosing starting at 400–600 mg/day and tapered over 21 days to 100–300 mg/day	Reduction in observer-rated AWS symptoms, reduction in alcohol craving	Grade C (level 3 evidence) for AWS

AW alcohol withdrawal, AWS alcohol withdrawal syndrome, DT delirium tremens, SR systematic review

^aLevels of evidence presented are based upon the US Preventive Services Task Force (USPSTF) Strength of Recommendation Taxonomy (SORT) approach to grading evidence in medical literature [124]. Levels of evidence include: Level 1: good-quality, patient-oriented evidence including SRs, meta-analyses, and well-designed randomized controlled trials with consistent findings. Level 2: limited-quality, patient-oriented evidence including lower-quality/less consistent SRs, meta-analyses, or clinical trials as well as cohort and case-control studies. Level 3: other evidence in the form of consensus guidelines, disease-oriented evidence, and case series. These levels of evidence are used to determine a strength of recommendation grades, which include A (good-quality patient-oriented evidence); B (limited-quality, patient-oriented evidence); C (other evidence); and no recommendation