Alcohol Withdrawal: When to Choose an Adjunctive Anticonvulsant

Beginning of article

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.

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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.

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Neurobiologic rationale

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 …