Benzodiazepines are the mainstay of alcohol detoxification treatment, with extensive evidence supporting their efficacy and relative safety. (1) The risk of benzodiazepine-alcohol interaction, however, and psychomotor and cognitive impairments associated with benzodiazepine use may limit early rehabilitation efforts in hospitalized patients. (2) Cross-tolerance with alcohol also limits benzodiazepines' potential benefit in outpatients with substance use disorders.
Adding anticonvulsants to acute benzodiazepine therapy has been shown to decrease alcohol withdrawal symptom severity, reduce seizure risk, and support recovery, particularly in patients with multiple alcohol withdrawal episodes. After detoxification, long-term anticonvulsant use may reduce relapse risk by decreasing post-cessation craving, without abuse liability. (3)
Although not all studies endorse adding anticonvulsants to benzodiazepines for managing alcohol withdrawal syndrome (AWS), (4) we present 3 cases in which anticonvulsants were used successfully as adjuncts to lorazepam. Valproic acid, levetiracetam, and gabapentin offer advantages in acute and long-term therapy of alcohol dependence with efficacy in AWS, low abuse potential, benign safety profile, and mood-stabilizing properties.
AWS manifests as a cluster of clinical symptoms including delirium tremens (DTs) and seizures (Table 1, page 28). Its pathophysiology can be explained by alcohol's agonist effect on the gamma-aminobutyric acid (GABA) system and antagonist effect on the glutamatergic system (Table 2, page 35).(5)
Table 1 Alcohol withdrawal: Acute vs long-term symptoms Alcohol withdrawal syndrome Protracted withdrawal syndrome Description Cluster of symptoms in Constellation of symptoms alcohol-dependent persons lasting weeks to months after heavy or prolonged after alcohol use ends alcohol use has lessened or ceased Presentation Develops during acute Develops after 5- to detoxification period and 7-day acute lasts 5 to 7 days detoxification period and may persist for 1 year Symptoms Mild: insomnia, tremor, Sleep disruption; anxiety, GI upset, anxiety; depressive headache, diaphoresis, symptoms; irritability; palpitations, anorexia increased breathing rate, Severe: alcoholic body temperature, blood Hallucinosis pressure, and pulse Seizures (generalized tonic-clonic) occur in up to 25% of withdrawal episodes, usually within 24 hours after alcohol cessation Delirium tremens (characterized by hallucinations, disorientation, tachycardia, hypertension, low-grade fever, agitation, and diaphoresis) occurs in up to 5% of patients undergoing withdrawal, may be delayed 4 to 5 days, and has mortality rates reaching 15% GI: gastroinestinal Source: For a bibliography, see this article at CurrentPsychiatry.com Table 2 How alcohol affects GABA and glutamate neurotransmitters GABA Glutamate GABA, the brain's primary Glutamate, the brain's major inhibitory neurotransmitter, excitatory neurotransmitter, renders nerve cells less sensitive renders nerve cells more to further signaling sensitive to further signaling Alcohol facilitates the inhibitory Alcohol seems to inhibit the function of the [GABA.sub.A] excitatory function of the NMDA receptor, allowing more GABA to glutamate receptor, believed to traverse the receptor, and leading play a role in memory, to alcohol's intoxicating effects learning, and generation of seizures During alcohol withdrawal, brain Long-term alcohol …