Gabapentin for Alcohol Withdrawal Syndrome

Phase 4

Completed

Conditions: Alcohol Withdrawal Syndrome

Interventions: Drug: Benzodiazepines
Drug: Gabapentin
Drug: Divalproex Sodium

Registration Number: NCT03012815

Lead Sponsor: Mayo Clinic

Brief Summary: The current "gold-standard" for the management of alcohol withdrawal syndrome (AWS) is symptom-triggered administration of benzodiazepines. This method of treatment has several drawbacks that have been described in the literature. Thus benzodiazepine sparing agents have been evaluated for use in AWS. One of these agents that has not only shown benefit for AWS but also benefits on complete abstinence, reducing a return to heavy drinking, and cravings is gabapentin. In clinical practice at Mayo Clinic gabapentin is used for this purpose. Due to the limited reports of the safety and efficacy of a protocol involving gabapentin for AWS, a study to compare gabapentin to symptom-triggered lorazepam will be completed.

Detailed Description: The current "gold-standard" for the management of alcohol withdrawal syndrome is symptom-triggered administration of benzodiazepines. Benzodiazepines and use of a symptom-triggered approach has several drawbacks such as over administration of medication due to many subjective patient reported symptoms. Benzodiazepines may contribute to a drug-induced delirium or high dosage may necessitate transfer to an ICU setting. Abrupt withdrawal of benzodiazepines also contribute to cravings, rebound insomnia, and anxiety that have been shown to increase the risk of a return drinking.

Clinical use of gabapentin for alcohol withdrawal has been presented by Maldonado at Stanford University Hospitals. (Academy of Psychosomatic Medicine Annual Meeting, 2013-2015) At Mayo Clinic, the Psychiatry Consultation-Liaison hospital service has been recommending the use of a modified gabapentin protocol since January 2015, which has been clinically accepted on medical, surgical, and psychiatric hospital services. The purpose of this research is to investigate the reactive benzodiazepine versus proactive gabapentin approaches to AWS in a prospective, randomized, open-label study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 88

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gabapentin	Divalproex Sodium	Patients will receive gabapentin taper over 9 days with the option to add divalproex for patients who have a history of seizures or severe withdrawal. Will still undergo CIWA-Ar scoring but will not be administered a benzodiazepine.
Benzodiazepine	Benzodiazepines	Patients will receive a benzodiazepine if scoring greater than 9 on the CIWA-Ar scale.
Gabapentin	Gabapentin	Patients will receive gabapentin taper over 9 days with the option to add divalproex for patients who have a history of seizures or severe withdrawal. Will still undergo CIWA-Ar scoring but will not be administered a benzodiazepine.

Primary Outcome Measures

Name	Time	Method
Mean Length of Hospital Stay	Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs.	The length of hospital stay for Alcohol withdrawal syndrome. The time interval between admission and either discharge or the time at which Clinical Institute Withdrawal Assessment - Alcohol revised (CIWA-Ar) scores are \<10 for 36 hours (up to 240 hours). Measured in hours. CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Zero to 7 points are assigned to each item, except for the last item, which is assigned 0-4 points, with a total possible score of 67. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores \> 8 represent more withdrawal symptoms and greater severity

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Delirium Tremens (DT)	During hospitalization (up to 240 hours)	The number of participants experiencing delirium tremens during their hospitalization (between admission and discharge).
Maximun Alcohol Withdrawal Severity Per CIWA-Ar Scale	4 days	CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Zero to 7 points are assigned to each item, except for the last item, which is assigned 0-4 points, with a total possible score of 67. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores \> 8 represent more withdrawal symptoms and greater severity
Change in Sleepiness as Assessed by the Epworth Sleepiness Scale	Baseline and 2 days	The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most people engage in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their daytime sleepiness.
Mean Total Benzodiazepine Use	Time to discharge or time to CIWA-Ar score < 10 for 36 hours (whichever came first) up to 240 hrs.	The total amount of benzodiazepines administered. Measured by lorazepam equivalent, mg.
Number of Participants Experiencing Seizure	During hospitalization (up to 240 hours).	The number of subjects who developed seizure during their hospitalization.
Change in Cravings as Assessed by the Penn Alcohol Craving (PACS) Scale	Baseline and 2 days	PACS is a 5 item self-rated scale of alcohol craving (0 = none to 6 = strong urge). Total scores range from 0 (little craving for alcohol) to 30 (irresistible urge to drink alcohol)
Change in Anxiety Symptoms as Measured by the Generalized Anxiety Disorder-7 (GAD-7) Scale	Baseline and 2 days	GAD-7 is GAD-7 is a 7-item self-administered scale of Generalized Anxiety Disorder symptoms (0 = not at all to 3 = nearly every day). Total scores range from 0 to 21. Total scores of 0-4 = minimal anxiety, Total scores of 5-9 = mild anxiety, total scores of 10-14 = moderate anxiety and total scores of 15-21 = severe anxiety.