Table 5
Pharmacologic profiles of benzodiazepines vs 3 anticonvulsants
| Benzodiazepines | Valproic acid | Levetiracetam | Gabapentin | |
|---|---|---|---|---|
| Metabolism | CYP 2C19: diazepam CYP 3A3/4: alprazolam, clonazepam, diazepam, triazolam Phase II only: lorazepam, temazepam, oxazepam | >95% hepatic, of which <20% occurs via CYP isoenzymes | Not extensively metabolized; renal clearance; not involved with hepatic CYP isoenzymes | Not metabolized; secreted via kidneys as unchanged drug |
| Sedation | Mild to moderate | Mild to moderate | Mild to moderate | Moderate to severe |
| Synergistic effects with alcohol | Yes | No | No | No |
| Paradoxical disinhibition | Yes | No | No | No |
| Risk of addiction in outpatient therapy | Yes | No | No | No |
| CYP: cytochrome P450 | ||||
| Source: Click here for a bibliography | ||||
CASE REPORT 2: Levetiracetam for withdrawal seizures
Mr. H, age 42, presents to the ER after suffering a seizure. His medical history includes hypertension, alcohol dependence, and seizures during alcohol withdrawal. He denies a history of psychiatric illness, and his family history is unknown. He is noncompliant with hypertension treatment, which includes clonidine. Mr. H reports his usual alcohol consumption as a 6-pack of beer nightly during the week and a 12-pack nightly on weekends. He says his last drink was 4 days before admission.
Mr. H scores 19 on the CIWA-Ar, placing him at risk for moderate withdrawal. Head CT shows diffuse atrophy, without evidence of an acute intracranial process. BAC is zero on admission, and urine drug screen is negative. Amylase, lipase, and lactate dehydrogenase (LDH) levels suggest acute pancreatitis. AST is elevated to 131 U/L, ALT is elevated to 42 U/L, but MCV is within normal limits.
The psychiatric service is consulted on day 2 of admission, and we prescribe levetiracetam, 500 mg IV every 8 hours.20 IV lorazepam also is available as needed: 1 mg every 8 hours for the first 2 days, then 1 mg every 12 hours for 2 days, then 1 mg every 24 hours. The patient’s CIWA-Ar score is 9 on days 2 and 3 of admission, followed by scores consistently between 2 and 3 after scheduled levetiracetam administration. Mr. H requires 3 mg of lorazepam the remainder of his hospitalization. He is discharged on day 7 with a CIWA-Ar score of 2, and reports no adverse effects related to levetiracetam. He leaves the hospital with a 2-week prescription for oral levetiracetam, 500 mg tid.
Advantages of levetiracetam
Levetiracetam is FDA-approved for adjunctive treatment of adults with partial-onset seizures.21 Successful AWS treatment with adjunctive levetiracetam has been supported by few but promising studies.10,20 Potential advantages of levetiracetam in detoxification include:
- a lack of GABAergic properties, which limits the risk of intoxication or respiratory insufficiency when combined with alcohol21
- low drug-drug interaction risk because of nonhepatic metabolism and primary renal excretion.22,23
We selected levetiracetam for Mr. H because of his history of alcohol withdrawal seizures and acute pancreatitis. Anticonvulsants may be more effective than lorazepam in reducing the risk of alcohol withdrawal seizures,24 and we felt valproic acid might not be safe for him because of its low but real risk of pancreatitis.13 We based our levetiracetam dosing on a small open-label trial20 and product information for treating adults with partial-onset seizures.25
Studies also demonstrate levetiracetam’s potential for relapse prevention during outpatient therapy. In a 10-week trial, levetiracetam decreased the number of standard drinks in alcohol-dependent patients from 5.3 to 1.7 per day.10 This was a small open trial, however, and large controlled trials support the usefulness of other, FDA-approved medications—including disulfiram, naltrexone, and acamprosate—for alcohol relapse prevention.
CASE REPORT 3: Gabapentin for acute withdrawal
Mr. B, age 38, presents to the ER after a 13-day alcohol binge. He has been drinking increasing amounts of alcohol over 6 weeks. Three months earlier, Mr. B was admitted for alcohol withdrawal treatment and received 49 mg of lorazepam over 3 days. This resulted in his transfer from the step-down unit to the intensive care unit for increased agitation, possibly caused by paradoxical disinhibition from excessive lorazepam use.26
Mr. B’s medical history is significant for alcohol-induced seizures, DTs, traumatic brain injury related to craniotomy, and right arm amputation. Mr. B drinks approximately 24 beers per day. He denies tobacco use but admits to past use of cocaine, marijuana, and heroin.
On admission, Mr. B’s BAC is 360 mg/dL (0.36%), AST is elevated at 72 U/L, ALT at 42 U/L, and LDH significantly elevated at 384 U/L. Urine drug screen is negative, and his CIWA-Ar score is 23. His score of –1 on the Richmond Agitation and Sedation Scale (RASS)27 correlates with very mild sedation.
Guided by Bonnet et al28 and clinical experience, we start Mr. B on gabapentin, 1,200 mg tid, and IV lorazepam, 2 mg every 8 hours as needed for breakthrough withdrawal. We decrease lorazepam by 50% every other day until Mr. B is discharged. On days 2, 3, and 4, Mr. B’s CIWA-Ar scores are 6, 9, and 2, respectively. His RASS score drops from –1 on days 1 and 2 to 0 until discharge, indicating an alert and calm state.