Medication Summary
Classically, benzodiazepines have been the medications of choice for treating symptoms of alcohol withdrawal. Flexibility of administration (eg, PO/IV/IM), rapid onset of action, and efficacy in sedating aggressive patients effectively provide treatment in emergencies. Risk of behavioral disinhibition and liver failure require caution.
Studies have shown promising findings from non-benzodiazepine alternatives, such as alpha-2 adrenergic agonists, gabapentin, depakote, and other anticonvulsants, to successfully treat alcohol withdrawal. [19]
Antipsychotics may lower the seizure threshold and, consequently, increase the risk of seizures associated with alcohol withdrawal. Thus, they should be considered second-line agents and only after hemodynamic stability and risks of alcohol withdrawal have been addressed with benzodiazepines. Typical antipsychotics (eg, haloperidol) effectively treat psychosis with acute agitation, which is at least partially attributed to their benefit of rapid tranquilization. High-potency antipsychotics are recommended for rapid tranquilization; lower-potency antipsychotics (eg, chlorpromazine) might require higher doses. Among atypical antipsychotics, olanzapine can be provided in both oral and intramuscular forms and is also effective in treating psychosis with acute agitation. For psychosis without acute agitation, the atypical antipsychotics (eg, risperidone, olanzapine, quetiapine, paliperidone, ziprasidone, aripiprazole) that are more tolerable can be used.
Other medications used in the treatment of alcohol use disorder include disulfiram for enforced abstinence, naltrexone or topiramate to dampen cravings, and naloxone if opiate overdose is suspected.
Topiramate doses of up to 300 mg have been studied for treating alcohol dependence. [21, 22]
For a study of the value of pharmacotherapy in the treatment of alcohol abuse and related psychiatric disorders, see Lev-Ran et al. [23]
Inpatient and outpatien medications
If the psychosis has resolved and the patient is medically stable, no further medication is needed.
If psychosis persists beyond elimination of the offending substance, an atypical antipsychotic drug (eg, risperidone, olanzapine, quetiapine) may be considered. No single atypical antipsychotic drug has been proven most beneficial for treatment of persistent alcohol-related psychosis.
Once thiamine levels have been restored, daily multivitamins are recommended to maintain appropriate levels of essential vitamins that often are depleted in patients with alcoholism.
Disulfiram (Antabuse) is an agent indicated to facilitate abstinence from alcohol. This can be started 12 hours after a patient consumes alcohol (125-500 mg/d).
Continue thiamine (100 mg PO tid).
Benzodiazepines
Class Summary
Benzodiazepine binding to the benzodiazepine receptor allosterically modulates the GABAA receptor to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmissions.
Lorazepam (Ativan)
Lorazepam is preferred over chlordiazepoxide (Librium) because the half-life in liver disease is more predictable (T ½=10-20 h). It does not undergo oxidative metabolism by the liver. Accumulation of the drug or its active metabolites does not occur. It is available in PO, IV, and IM forms.
Chlordiazepoxide (Librium)
Chlordiazepoxide provides rapid onset and efficacy in sedating aggressive patients. It has a longer half-life (>21 hours), providing a steady withdrawal. It is available in PO, IV, and IM forms.
Antipsychotics
Class Summary
High-potency classic agents (eg, haloperidol) provide rapid, predictable, and effective sedation in the management of acutely psychotic patients. They are less sedating and are more easily titrated but are more likely to cause extrapyramidal adverse effects than the lower-potency agents. They often are combined in the same syringe with a benzodiazepine (eg, lorazepam, diazepam) for better sedation and anxiolysis and less dystonia or akathisia. They are given IM or IV, or, in a less acute setting, they are given PO. Haloperidol also has a monthly depot form (Haldol Decanoate). Depot antipsychotics are not intended for use in the acute setting.
Haloperidol (Haldol)
Haloperidol controls psychosis and provides rapid tranquilization. Administer it with a benzodiazepine to protect against lowered seizure threshold. In emergencies, select a high-potency antipsychotic available in PO (tablet, liquid) or IM form.
Chlorpromazine (Thorazine)
Chlorpromazine blocks postsynaptic blockade of the central nervous system dopamine receptors, inhibiting dopamine-mediated effects. It provides rapid tranquilization in PO and IM forms.
Antialcoholic agents
Class Summary
A patient who is highly motivated to participate in an abstinence program may benefit from the use of disulfiram. Disulfiram inhibits the metabolism of alcohol, causing increased levels of acetaldehyde, resulting in flushing, nausea, and multiple other noxious symptoms. Compliance can be determined through detecting diethylamine (disulfiram metabolite) in the urine. Naltrexone is an agent helpful in decreasing the craving for alcohol. It has been shown to be superior to placebo when used in combination with supportive psychotherapy. Naltrexone's mechanism of action is thought to be through blocking the opioid system, which is thought to be involved in alcohol craving. Acamprosate is the newest approved drug. Its mechanism of action is not fully understood, but it is hypothesized to restore neuronal excitation and inhibition balance.
Disulfiram (Antabuse)
Disulfiram is used to enforce abstinence but does not cure alcoholism. It is often used in conjunction with psychotherapy and AA meetings.
Naltrexone (ReVia)
Naltrexone is used primarily to block the opioid receptors and prevent euphoria (thus decreasing craving) in those who abuse opiates. Theoretically, when a person with alcoholism craves alcohol, the opioid system is stimulated and the opioid receptors are antagonized, thus, the craving is dampened.
Acamprosate (Campral)
Acamprosate is a synthetic compound with a chemical structure similar to that of the endogenous amino acid homotaurine (structural analogue of GABA). The mechanism of action to maintain alcohol abstinence is not completely understood. It is hypothesized to interact with glutamate and GABA neurotransmitters centrally to restore neuronal excitation and inhibition balance. It is not associated with tolerance or dependence development. It does not eliminate or diminish alcohol withdrawal symptoms. It is indicated to maintain alcohol abstinence as part of a comprehensive management program that includes psychosocial support. It is available as a 333-mg tablet.
Atypical antipsychotics
Class Summary
These agents provide a number of major improvements over the traditional agents, including the following: fewer adverse anticholinergic effects, less dystonia and parkinsonism, very low risk of tardive dyskinesia, and potential reversal of many negative symptoms (eg, affective blunting, alogia, withdrawal, avolition). These agents affect dopamine receptors but also affect serotonin receptors involved with frontal lobe functions.
Ziprasidone (Geodon)
Ziprasidone antagonizes dopamine D2, D3, 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1D, alpha1 adrenergic receptors. It has a moderate antagonistic effect for histamine H1. It moderately inhibits reuptake of serotonin and norepinephrine.
Aripiprazole (Abilify)
Aripiprazole improves positive and negative schizophrenic symptoms. The mechanism of action is unknown but is hypothesized to work differently from other antipsychotics. Aripiprazole is thought to be a partial dopamine (D2) and serotonin (5HT1A) agonist and to antagonize serotonin (5HT2A). Additionally, no QTc interval prolongation was noted in clinical trials. It is available as tablet, orally disintegrating tablet, or oral solution.
Olanzapine (Zyprexa)
Olanzapine may inhibit serotonin, muscarinic, and dopamine effects. Its efficacy is similar to risperidone, with fewer dose-dependent adverse effects but more concern about weight gain.
Quetiapine (Seroquel)
Quetiapine may act by antagonizing dopamine and serotonin effects. Its efficacy is similar to risperidone and olanzapine. It has fewer dose-dependent adverse effects and less concern of weight gain compared with clozapine and olanzapine.
Risperidone (Risperdal)
Risperidone, unlike haloperidol, has serotonergic (5-HT2)-blocking effects that alleviate negative symptoms of psychosis (eg, anhedonia, avolition, amotivational, flat effect). It is well tolerated with fewer adverse extrapyramidal effects than typical antipsychotics. Doses larger than 6 mg/d increase the risk of extrapyramidal effects. No atypical antipsychotic agent is preferred in treating alcohol-related psychosis.
Narcotic antagonists
Class Summary
Naloxone acts similar to naltrexone as an opiate receptor antagonist but has significant differences, restricting it to emergency situations of opiate overdose. It also should be considered in patients with alcoholism who have altered mental status due to overdose of opiates. Naloxone is poorly absorbed PO and should be administered IM or IV.
Naloxone (Narcan)
Naloxone is used in emergencies in which narcotic overdose results in respiratory depression. It is available in IV, IM, and SC forms.
