Alcohol Withdrawal
Conditions
Brief summary
A randomized, double-blind controlled trial comparing treatment outcomes between chlordiazepoxide, or gabapentin to treat alcohol withdrawal syndrome in alcohol dependent veteran subjects. The objective of this trial is to compare the safety and effectiveness of these two medications. Intervention is a fixed dose taper of chlordiazepoxide, or gabapentin over 6 days. Subjects will be evaluated for 7-10 days to monitor alcohol abstinence, withdrawal severity scores, adverse events including ataxia, sedation, cognitive function and alcohol craving.
Detailed description
Chlordiazepoxide 25 mg and matching placebo capsules or gabapentin 300 mg and matching placebo capsules were were used. The chlordiazepoxide/placebo and gabapentin/placebo capsules were not identical in appearance. Study medications were packaged into a 7-day medication organizer. The dosing for each subject was either gabapentin 1200mg or chlordiazepoxide 100 mg orally days 1-3, gabapentin 900 mg or chlordiazepoxide 75 mg day 4, gabapentin 600 mg or chlordiazepoxide 50 mg day 5, and gabapentin 300 mg or chlordiazepoxide 25 mg day 6. Adherence was assessed by pill counts and serum samples were obtained for study drug analysis. Serum samples were batched and sent to a contract laboratory so that study clinicians were blinded to the results until after the trial was completed. Presence of the assigned study medication in the blood served as a surrogate adherence marker. Subjects also received prescriptions for daily oral therapeutic multiple vitamin tablets, folic acid 1 mg, and thiamine 100 mg. A psychiatric history and physical examination, breath alcohol concentration, vital signs, CIWA-Ar (alcohol withdrawal scale), and blood chemistry including transaminases and complete blood cell count were obtained for baseline for all participants. Subjects were seen on weekdays for clinic follow-up appointments. Assessments performed at each study visit included CIWA-Ar, ESS (Epworth Sleepiness Scale), PACS (Penn Alcohol Craving Scale), and a brief examination to document mental status and assess coordination, which included assessment of stance, tandem gait, Romberg test, pronator drift, toe and heel walk, rapid-alternating-movements, and point-to-point movements. Breath alcohol concentration (BAC) was also measured (AlcoSensor, Intoximeters, Inc.) at each visit.
Interventions
DRUGChlordiazepoxide
25mg four times daily x 3 days then tapered over 3 days
DRUGGabapentin
300mg four times daily x 3 days then tapered over 3 days
Sponsors
VA Salt Lake City Health Care System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Alcohol dependent at risk for withdrawal symptoms
Exclusion criteria
* Benzodiazepine dependent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epworth Sleepiness Scale (ESS) | 1 week | ESS is an 8 item-scale and scores range between 0 and 24. The higher the score implies more daytime sleepiness. |
| PENN Alcohol Craving Scale | 1 week | PENN is a 5 item self-rated scale of alcohol craving. Scores range from 0 (little craving for alcohol) to 30 (irresistable urge to drink alcohol) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Institute Withdrawal Assessment-Alcohol (Revised)(CIWA-Ar) | 1 week | CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Many previously publications suggest a total score of 8-10 is severe enough to warrant medication treatment. Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores \> 8 represent more withdrawal symptoms and greater severity |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from VA outpatient detoxification clinic
Pre-assignment details
Exclusions: subjects requiring hospitalization, receiving benzodiazepines prior to randomization and subjects not likely to follow instructions.
Participants by arm
| Arm | Count |
|---|---|
| Chlordiazepoxide 25mg qid x 3 days, 25mg tid x 1 day, 25mg bid x 1 day, 25mg hs x 1 day then d/c | 9 |
| Gabapentin 300mg qid x 3 days, 300mg tid x 1 day, 300mg bid x 1 day, 300mg hs x 1 day then d/c | 17 |
| Total | 26 |
Baseline characteristics
| Characteristic | Chlordiazepoxide | Gabapentin | Total |
|---|---|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 4.8 | 51.1 years STANDARD_DEVIATION 7.7 | 52.7 years STANDARD_DEVIATION 6.6 |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 17 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 17 |
| serious Total, serious adverse events | 0 / 9 | 0 / 17 |
Outcome results
Primary
Epworth Sleepiness Scale (ESS)
ESS is an 8 item-scale and scores range between 0 and 24. The higher the score implies more daytime sleepiness.
Time frame: 1 week
Population: Late withdrawal period days 5-7
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chlordiazepoxide | Epworth Sleepiness Scale (ESS) | 6.35 units on a scale |
| Gabapentin | Epworth Sleepiness Scale (ESS) | 2.65 units on a scale |
Primary
PENN Alcohol Craving Scale
PENN is a 5 item self-rated scale of alcohol craving. Scores range from 0 (little craving for alcohol) to 30 (irresistable urge to drink alcohol)
Time frame: 1 week
Population: Late withdrawal period days 5-7
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chlordiazepoxide | PENN Alcohol Craving Scale | 16.78 units on a scale |
| Gabapentin | PENN Alcohol Craving Scale | 10.74 units on a scale |
Secondary
Clinical Institute Withdrawal Assessment-Alcohol (Revised)(CIWA-Ar)
CIWA-Ar measures severity of 10 observed or measured alcohol withdrawal signs or symptoms. Total score ranges from 0 (best possible outcome)-67 (worst possible outcome). Many previously publications suggest a total score of 8-10 is severe enough to warrant medication treatment. Lower scores (0-8) represent fewer withdrawal symptoms and less severity, scores \> 8 represent more withdrawal symptoms and greater severity
Time frame: 1 week
Population: Late withdrawal period days 5-7
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chlordiazepoxide | Clinical Institute Withdrawal Assessment-Alcohol (Revised)(CIWA-Ar) | 3.29 units on a scale |
| Gabapentin | Clinical Institute Withdrawal Assessment-Alcohol (Revised)(CIWA-Ar) | 4.33 units on a scale |