Alcohol-Related Psychosis



Alcohol-related psychosis is a secondary psychosis that manifests as prominent hallucinations and delusions occurring in a variety of alcohol-related conditions. For patients with alcohol use disorder, previously known as alcohol abuse and alcohol dependence, psychosis can occur during phases of acute intoxication or withdrawal, with or without delirium tremens. In addition, alcohol hallucinosis and alcoholic paranoia are 2 uncommon alcohol-induced psychotic disorders, which are seen only in chronic alcoholics who have years of severe and heavy drinking.[1] Lastly, psychosis can also occur during alcohol intoxication, also known as pathologic intoxication, an uncommon condition the diagnosis of which is considered controversial.[2, 3]

In chronic alcoholic patients, lack of thiamine is a common condition. Thiamine deficiency is known to lead to Wernicke-Korsakoff syndrome, which is characterized by neurological findings on examination and a confusional-apathetic state. Korsakoff psychosis (or Korsakoff amnesic- or amnesic-confabulatory state) refers to a state that memory and learning are affected out of proportion to other cognitive functions in an otherwise alert and responsive patient.[4]

Alcohol is a neurotoxin that damages the brain in a complex manner through prolonged exposure and repeated withdrawal, resulting in significant morbidity and mortality. Alcohol-related psychosis is often an indication of chronic alcoholism; thus, it is associated with medical, neurological, and psychosocial complications.

Alcohol-related psychosis spontaneously clears with discontinuation of alcohol use and may resume during repeated alcohol exposure. Distinguishing alcohol-related psychosis from schizophrenia or other primary psychotic disorders through clinical presentation often is difficult. It is generally accepted that alcohol-related psychosis remits with abstinence, unlike schizophrenia. If persistent psychosis develops, diagnostic confusion can result. Comorbid psychotic disorders (eg, schizophrenia spectrum and other psychotic disorders) and severe mood disorder with psychosis may exist, resulting in the psychosis being attributed to the wrong etiology.

Some characteristics that may help differentiate alcohol-induced psychosis from schizophrenia are that alcohol-induced psychosis shows later onset of psychosis, higher levels of depressive and anxiety symptoms, fewer negative and disorganized symptoms, better insight and judgment towards psychotic symptoms, and less functional impairment.[5]

Alcohol idiosyncratic intoxication is an unusual condition that occurs when a small amount of alcohol produces intoxication that results in aggression, impaired consciousness, prolonged sleep, transient hallucinations, illusions, and delusions. These episodes occur rapidly, can last from only a few minutes to hours, and are followed by amnesia. Alcohol idiosyncratic intoxication often occurs in elderly persons and those with impaired impulse control.

Unlike alcoholism, alcohol-related psychosis lacks the in-depth research needed to understand its pathophysiology, demographics, characteristics, and treatment. This article attempts to provide as much possible information for adequate knowledge of alcohol-related psychosis and the most up-to-date treatment.

Case examples

Case 1: A 37-year-old white male infantryman stationed in Iraq arrived at a field hospital complaining that his superior officer placed poisonous ants in his helmet. His face is covered with excoriations from persistent scratching. On further examination, he is stuporous and has mildly slurred speech, tremor, and mint odor to his breath. Later his troop leader mentioned that his Humvee was littered with empty bottles of mouthwash and that the man has been reprimanded for falling asleep at his post. After a night of rest, he discussed his excessive use of mouthwash in place of alcohol, which is the only available form of alcohol in Iraq.

Case 2: At 5 pm you are asked to consult on a 44-year-old white female who is 2 days postsurgical hysterectomy. She is complaining of rabbits running across the room and demands the nurses stop intruding "every minute of every hour." She is tremulous, disoriented to time and place, and irritable. A review of her laboratory data shows an elevated gamma-glutamyl transferase (GGT) and slightly elevated liver function test values. White blood cell count is normal. Urinalysis is normal and blood alcohol level is 0.01. Her medications, which were held prior to the surgery, included acamprosate 666 mg three times daily and clonazepam 1 mg 4 times a day. Her sister later informs the nursing staff that this woman is usually on her fourth Manhattan cocktail by this hour of the day.


Ethanol is a small molecule that readily distributes to the brain and reaches peak levels in blood approximately 30 minutes after ingestion of an alcoholic drink. Ethanol affects proteins that are associated with a wide variety of neurotransmitters and pathways. These include the dopamine pathway, serotonin pathway, proteins associated with GABAA receptor, glutamate receptors (ie, N -methyl-D-aspartate [NMDA]/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]/Kainate), mGlu receptors, nicotinic receptors, cannabinoid CB1 receptors, voltage-gated calcium ion channels, and calcium-activated potassium channels.[6]

Like other psychotic disorders, the exact etiology of alcohol-related psychosis remains unclear, but most likely it is related to dopamine in the limbic and possibly other systems, such as the glutamatergic neurotransmitter system. The dopamine hypothesis often is applied to psychosis involving excessive activity of the dopaminergic system. Animal studies have shown dopaminergic activity to increase with increased release of dopamine when alcohol is administered.

On the other hand, alcohol withdrawal generates a decrease in the firing of dopaminergic neurons in the ventral tegmental area and a decrease in the release of dopamine from the neuron. Ethanol acutely disrupts glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Prolonged inhibition of the NMDA receptor by ethanol leads to supersensitivity. During the phase of withdrawal, acute removal of ethanol causes marked augmentation of activity of postsynaptic neurons, such as those in the noradrenergic system, and, in the extreme, glutamate-induced excitotoxicity.[6, 7]

The pathophysiologies of intoxication, withdrawal, and alcohol idiosyncratic intoxication are all are different, and their exact relationships to psychosis are unclear, but one can certainly postulate the underlying mechanisms are complex, considering alcohol’s broad impact on a variety of neurotransmitter pathways. To some degree, they all involve the neurotoxicity of alcohol and its damage at the genetic, biochemical, and cellular levels leading to physiological and neurological pathology.

Depending on the individual and amount consumed, alcohol intoxication can result in disinhibition, sedation, and anesthesia or even coma by acute depression of the cerebral cortex and reticular activating system. The pathophysiology of alcoholism involves alterations in short-term membrane regulation and long-term effects on gene expression at the cellular level.

In patients who are dependent on alcohol, alcohol withdrawal results in adrenergic hypersensitivity of the limbic system and brainstem. Thiamine deficiency also is a contributing factor and is known to be associated with more severe episodes of withdrawal psychosis, which may present as a delirious state known as Wernicke-Korsakoff syndrome. The psychosis often is self-limited and recurs with subsequent withdrawals.



United States

Roughly 3% of persons with alcoholism experience psychosis during acute intoxication or withdrawal. Approximately 10% of patients who are dependent on alcohol and are in withdrawal experience severe withdrawal symptomatology, including psychosis. Twins studies have shown concordance rates for alcohol-related psychosis to be 17.3% in monozygotic twins and 4.8% in dizygotictwins.[8]

Those with first-episode psychosis are twice more likely than the general population to present with comorbid substance abuse and are more commonly males than females. The most commonly reported substance is cannabis (51%) followed by alcohol (43%).[9]


In as much as 50% of Japanese, Chinese, and Korean populations, the likelihood of alcohol-related disorders occurring is less because of the absence of aldehyde dehydrogenase. This causes an Antabuse-like reaction involving facial flushing and palpitations.

Studies of the Soviet Slavic Republic of Belarus from 1970-2005 suggest a correlation between cultural and social context of alcohol consumption and alcohol-related suicides and alcohol-induced psychosis.[10] Furthermore, there appears to be a close correlation between alcohol psychosis and higher mortality rates compared with alcohol consumption and no psychosis. Studies on alcohol consumption and psychosis are easier to study in Belarus as they are among highest consumers of alcohol in the world, with an annual consumption of 14 liters per capita per year.[11]


The appearance of alcohol-related psychosis usually occurs with long-term alcohol use disorder; therefore, it is associated with the same morbidity and mortality of long-term alcoholism. The presence of alcohol-related psychosis is a serious indicator of medical, neurological, and psychosocial complications that can hinder appropriate treatment and lead to negative outcomes. The prognosis for alcohol-related psychosis with treatment is considered good, with only 10-20% of psychosis cases becoming chronic. Alcohol-related psychosis itself does not have specific morbidity or mortality; instead, it correlates with a cluster of risk factors that indicate higher morbidity and mortality in patients with alcoholism.[12]

Psychiatric complications of alcohol-related psychosis include higher rates of depression, anxiety, and suicide. The potential for violence also exists.

Alcohol-related psychosis that does not remit with abstinence may indicate undiagnosed schizophrenia or other psychotic disorders. Contrary to amphetamine-induced psychosis, alcohol-induced psychosis tends to be short-lived and is much less likely to be chronic. The use of alcohol may potentiate or initiate psychosis through kindling, a process where repetitive neurologic insult results in greater expression of the disease.

Substance abuse is a major contributing factor to the outcome and course of treatment in mentally ill patients with psychosis. The prevalence is up to 87% in those with schizophrenia and 77% in those who are bipolar, with cannabis and alcohol being the most commonly abused.[13]

Some of the medical complications observed with alcohol-related psychosis and chronic alcoholism include liver disease, pulmonary tuberculosis, diabetes mellitus, musculoskeletal injury, hypertension, and cerebrovascular disease.

With intoxication, mortality is associated with the alcohol level in the blood. A blood alcohol level (BAL) greater than 400 mg/dL in nontolerant individuals can result in lethal respiratory arrest.[14]

In withdrawal, auditory hallucinations can be indicative of early-stage withdrawal (6-24 h), the stage associated with withdrawal seizures. Symptoms of visual, auditory, and tactile hallucinations are indicative of late-stage withdrawal (36-72 h), the stage associated with delirium tremens and a mortality rate of 5-15%.

Neurologic abnormalities may clear in 20% of patients with Wernicke-Korsakoff syndrome who receive treatment with thiamine and who abstain from consuming alcohol.[15]


Cultural influences on alcohol-related psychosis stem from cultural norms about alcohol. Irish males who traditionally drink to the point of intoxication are at higher risk, while Jewish males who traditionally shun intoxication have lower risks. Considering the relationship of thiamine to Wernicke-Korsakoff syndrome, cultures that have a low intake of thiamine and high rates of alcohol abuse also are at higher risk for the complication of Wernicke-Korsakoff syndrome.


Alcohol abuse and dependency has a male-to-female ratio of 5:1. Females develop alcohol-related disorders later in life because they start heavy use later than males.


Alcohol-related psychosis occurs after extended periods of alcohol abuse that result in an alteration of neuronal membranes, genetic expression, and thiamine deficiency. Early-onset alcoholism results in a greater chance of complications earlier in life and an outcome that is influenced by psychosocial function. Late-onset alcoholism only delays the onset of complications. As a general rule, alcohol-related psychosis occurs more frequently in older populations. Most alcohol-related disorders have an onset in persons aged 35-40 years.


Alcohol-related psychosis can be confused with other psychiatric manifestations resulting from other substance use and/or from other medical, neurological, and psychological etiologies. The determination of cause of alcohol-related psychosis can be facilitated by thoroughly reviewing the patient’s history of clinical symptoms, course of development, and other pertinent information such as family genealogy.

The Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) provides criteria for the diagnosis of substance-induced psychotic disorder and should be helpful in clarifying etiology.[16]

DSM-5 criteria for substance-induced psychotic disorder

Prominent hallucinations or delusions are present. Hallucinations are false sensations. In this case, they are often visual, but can also be tactile or auditory hallucinations or illusions. Delusions are false ideas. Paranoia and occasionally grandiosity may be the delusions engaged here.

Evidence from the history, physical examination, or laboratory findings indicates both (1) the hallucinations or delusions developed during or soon after (eg, within a month of) substance intoxication or withdrawal or (2) substance used is etiologically related to the disturbance.

The disturbance is not better accounted for by a psychotic disorder that is not substance-induced. Evidence that the symptoms are better accounted for by a psychotic disorder that is not substance-induced might (1) the symptoms precede the onset of the substance use, (2) the symptoms persist for a substantial period (eg, a month) after cessation of acute withdrawal or severe intoxication, or (3) the symptoms are substantially in excess of what would be expected given the type or amount of the substance use or the duration of use.

Other evidence suggests the existence of an independent non–substance-induced psychotic disorder (eg, a history of recurrent non–substance-related episodes).

The disturbance does not occur exclusively during the course of a delirium.

The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Note: When making a DSM-5 diagnosis of substance-induced psychotic disorder, specify the following:

Developmental history

Developmental history is useful for gathering information on in-utero exposure to medication, drugs, alcohol, pathogens, and trauma. As children, patients may have shown prodromal symptoms of a psychotic disorder, such as social isolation, deteriorating school performance, mood lability, amotivation, avolition, and anhedonia.

Development suggestive of alcohol-related psychosis involves delinquency, truancy, educational failure, early use of drugs and alcohol, and oppositional defiant or conduct disorder.

Psychiatric history

Determine whether a psychiatric disorder or symptoms ever occurred when patients were not exposed to alcohol.

Determine whether patients ever had a psychiatric disorder or similar symptoms related to any other drug or medication.

Recent history

The patient's history of alcohol abuse is extremely significant and is determined by the following questions:

Substance abuse history

Potentially abused substances include amphetamines, cocaine, piperidines (eg, phencyclidine [PCP], ketamine ), phenylethylamines (eg, 3,4-methylenedioxymethamphetamine [MDMA] or ecstasy/XTC), ergot alkaloids (eg, lysergic acid diethylamide or [LSD]), cannabis, over-the-counter (OTC) sympathomimetics (eg, dextromethorphan [DXM]), steroids, L-dopa, nonalcohol sedative hypnotics (eg, benzodiazepine), and opiate pain medications.

Family history

Family history (including substance abuse, alcoholism, and mental illness) of psychotic disorders in the absence of alcohol suggests a primary psychiatric disorder. If no family history of psychiatric disorders is present, a diagnosis of alcohol-related psychosis can be supported.

Family history of alcoholism increase the risk of alcoholism to 3- to 4-fold.[17]


During the initial examination of every psychiatric patient, a full physical and neurological examination is strongly recommended. When a patient presents as psychotic or intoxicated, also assess the risk of dangerous behavior.


The first step in evaluating an intoxicated patient is the initial assessment for medical stability (eg, alertness, breathing, circulation), including vital signs, blood pressure, pulse, and temperature.

This is followed by an assessment for physical signs of a variety of medical complications of alcoholism (eg, blood dyscrasias, liver failure, cardiomyopathy, gastric tumors, injuries from falls). A comprehensive laboratory evaluation can assist in diagnosing medical complications.


Head injury may have occurred from a fall, altering the neurological status of the individual.

Other complications, such as peripheral neuropathy, amnesia, ataxia, and ophthalmoplegia, also can be evaluated.

Mental status

Evaluation of the mental status should focus on orientation, memory, signs of delirium, hallucinations, and delusions, as well as affect with risk of assessment for violence and suicide. Checking the mental status frequently is important, as the affect and level of consciousness may fluctuate dramatically.

A mental status examination may appear as follows for intoxication with psychosis:

Mental status examination for alcohol withdrawal and psychosis may appear as follows:

Dangerous behaviors

Assess patients for the potential for assault or self-harm.


Possible causes or contributors to alcohol-related psychosis include the following:

It is important to also evaluate the use of nontraditional methods of alcohol consumption. A study of intoxication in a combat theater, where alcohol is prohibited, showed that unexplained psychosis may be the result of consumption of mouthwash. Nonprescription brands of mouthwash can contain up to 23.40% ethanol by volume.[18]

Laboratory Studies

The purpose of the workup is to eliminate other possible causes of psychosis, altered mental status, and medical complications. Laboratory evaluation should include the following:

Imaging Studies

If a head injury is suspected, a CT scan is recommended to rule out a subdural hematoma.

In those with comorbid schizophrenia and alcoholism, MRIs have shown that the gray matter volume deficits in the prefrontal and anterior superior temporal regions is greater than in those with schizophrenia and alcoholism alone.

Chest radiography can be considered for all homeless patients, elderly patients, and patients with risk factors for tuberculosis.

Other Tests

Some other tests that might be administered include a Brief Psychotic Rating Scale (BPRS), Beck Depression Scale, Violence and Suicide Assessment (VASA), and Mini-Mental State Examination. Other measures also might be useful.

If persistent psychosis is noted, neuropsychological testing to assess the level of psychosocial and neurological function can be beneficial for treatment and placement.

Projective testing, such as the Rorschach and the Thematic Apperception Test, can clarify a thought disorder.

Medical Care

Because most cases of alcohol-related psychosis are self-limiting, removal of alcohol should suffice.

The initial treatment of patients with alcohol intoxication or withdrawal should focus on medically stabilizing the patient by assessing respiratory, circulatory, and neurological systems. An intoxicated patient or one undergoing withdrawal to the point with psychosis should be considered a medical emergency because of the risks of unconsciousness, seizures, and delirium. Medical treatment should focus on the effect of alcohol on the body as a whole. A patient with head trauma may be misdiagnosed with Wernicke-Korsakoff syndrome, and a neurologic examination should always be considered. Alcohol withdrawal requires inpatient hospitalization for more than 72 hours after the risk of delirium tremens has subsided.

Alcohol withdrawal psychosis is a symptom of alcohol withdrawal and should be treated in the context of alcohol withdrawal. Treatment is initiated with cautious use of oral or intramuscular benzodiazepines. Lorazepam (Ativan) at 1-2 mg or chlordiazepoxide (Librium) at 25-50 mg PO or IM is used commonly and frequently under the guidance of Clinical Institute Withdrawal Assessment (CIWA) of Alcohol Scale. The dose of benzodiazepine is tapered over the next 5-7 days. Studies have shown promising findings from non-benzodiazepine alternatives to successfully treat alcohol withdrawal.[19]

In the event patients are in danger of harming themselves or others, rapid sedation should be initiated with a high-potency antipsychotic drug such as haloperidol (Haldol) at 5-10 mg PO or IM, frequently given with anticholinergics, benztropine (Cogentin) (1-2 mg) or diphenhydramine (Benadryl) (25-50 mg); both can be given PO or IM to prevent extrapyramidal adverse effects.

Antipsychotics may lower the seizure threshold and should not be used to treat withdrawal symptoms unless absolutely necessary and used in combination with a benzodiazepine or antiseizure medications (eg, valproic acid [Depakote] or carbamazepine [Tegretol]).

Nonmedical treatment includes the use of mechanical wrist and leg restraints if acute danger of assault or self-harm is not managed adequately by chemical restraints alone.

Treatment may include thiamine at 100 mg parentally followed by supplemental thiamine at 100 mg 3 times a day, folic acid at 1 mg, and a daily multivitamin.

In case of a suspected opiate overdose, administer naloxone (Narcan) at 0.4-2 mg IV, IM, SC, or endotracheally.


Neurologist consultation can assist in the evaluation of the patient's neurological status to rule out neurological consequences of alcohol (ie, peripheral neuropathy, Wernicke-Korsakoff syndrome, seizures, postictal states, encephalitis, subdural hematoma).

An internal medicine specialist can provide extended care to patients with a blood dyscrasia, electrolyte abnormality, thiamine deficiency, gastric tumors, or diabetes.

Psychiatrist and social services counselor can assist with inpatient treatment for substance abuse or further psychiatric stabilization.[20]

The patient and family need education about alcohol and referral to Alcoholics Anonymous (AA) and family supports. Social services personnel can help with outpatient services (eg, AA, sober houses, provider appointments). Family issues may be involved, and social services counselors can be helpful in providing supportive and directive care.


No specific dietary restrictions are necessary. However, if a patient has a thiamine-poor diet, further dietary intake should be normalized.


A patient intoxicated with alcohol or with severe alcohol withdrawal symptoms frequently has ataxia and can with waxing and waning sensorium and consequently are at risk for falls. Limit the activity of such patients until symptoms have resolved.

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]

Lorazepam (Ativan)

Clinical Context:  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)

Clinical Context:  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.

Class Summary

Benzodiazepine binding to the benzodiazepine receptor allosterically modulates the GABAA receptor to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmissions.

Haloperidol (Haldol)

Clinical Context:  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)

Clinical Context:  Chlorpromazine blocks postsynaptic blockade of the central nervous system dopamine receptors, inhibiting dopamine-mediated effects. It provides rapid tranquilization in PO and IM forms.

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.

Disulfiram (Antabuse)

Clinical Context:  Disulfiram is used to enforce abstinence but does not cure alcoholism. It is often used in conjunction with psychotherapy and AA meetings.

Naltrexone (ReVia)

Clinical Context:  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)

Clinical Context:  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.

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.

Ziprasidone (Geodon)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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.

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.

Naloxone (Narcan)

Clinical Context:  Naloxone is used in emergencies in which narcotic overdose results in respiratory depression. It is available in IV, IM, and SC forms.

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.

Further Outpatient Care

A day treatment program or partial hospitalization can be used for those who do not require a highly structured inpatient environment. Daily individual, group, and weekly family therapy provide intensive treatment that is similar to inpatient settings. Programs specifically designed for substance abuse also provide daily substance abuse meetings and education. Medication evaluations and monitoring assure stabilization in the least restrictive environment.

Institute a psychiatric follow-up visit within 2 weeks of the initial evaluation to assure compliance.

Consider a follow-up examination with a neurologist or internal medicine specialist, depending on the complications of alcohol abuse.

Carefully monitor patients for recurring psychosis, depression, and relapse of alcohol use.

Further Inpatient Care

Admit for observation if further withdrawal, cognitive impairment, psychosis, and medical complications occur.

Inpatient & Outpatient 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).


If psychosis persists past initial treatment, the patient may be suffering from an undiagnosed psychotic disorder, such as schizophrenia or bipolar affective disorder. Inpatient psychiatric hospitalization may be required for diagnosis and psychopharmacological treatment.

If a risk of delirium tremens or suicide is present, transferring the patient to a psychiatric inpatient unit might be required.

A day treatment program or partial hospitalization can be used for those who do not require a highly structured inpatient environment. Daily individual, group, and weekly family therapy is provided. Programs specifically designed for substance abuse also provide daily substance abuse meetings and education. Medication evaluations and monitoring assure stabilization in the least restrictive environment.


Prevention is a result of abstinence and is the primary treatment of choice. Some patients may achieve success by attending 90 AA meetings in 90 days.

A sponsor (a recovering alcoholic committed to sobriety) helps provide a support network for attending meetings and seeking community resources.


Theoretically, alcohol may potentiate or initiate a psychotic disorder, such as schizophrenia, through kindling, a process where repetitive neurological insult results in greater expression of disease.

In some instances, psychosis may persist and may be considered by DSM-V criteria as a substance-induced psychotic disorder.

Other complications may include increased risks for suicide, depression, and/or psychosocial impairment.


Alcohol-related psychosis is indicative of severe alcohol abuse and suggests a poor prognosis. The prognosis is similar to that of severe alcoholism.

Of all psychosis cases, an estimated 10-20% tend to become permanent.

Symptoms of any accompanying Korsakoff syndrome (amnestic disorder) are highly resistant to treatment because of the irreversible neurological damage.

Patient Education

Refer the patient to AA, Smart Recovery, Rational Recovery, or other appropriate self-help group.

Refer the patient for psychosocial counseling.

Instruct the patient to abstain from the use of alcohol and illicit drugs.

Refer the patient's family to Al-Anon/Alateen and family therapy.

For excellent patient education resources, visit eMedicineHealth's Mental Health Center. Also, see eMedicineHealth's patient education articles Alcoholism, Alcohol Intoxication, and Substance Abuse.

The following Web sites are also useful:


Zhongshu Yang, MD, PhD, Associate Physician, Department of Adult Psychiatry, San Jose Medical Center, The Permanente Medical Group, Inc

Disclosure: Nothing to disclose.


Glen L Xiong, MD, Associate Clinical Professor, Department of Psychiatry and Behavioral Sciences, Department of Internal Medicine, University of California, Davis, School of Medicine; Medical Director, Sacramento County Mental Health Treatment Center

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Doctor On Demand<br/>Received income in an amount equal to or greater than $250 from: Blue Cross Blue Shield Federal Employee Program<br/>Received royalty from Lippincott Williams & Wilkins for book editor; Received grant/research funds from National Alliance for Research in Schizophrenia and Depression for independent contractor; Received consulting fee from Blue Cross Blue Shield Association for consulting. for: Received book royalty from American Psychiatric Publishing Inc.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Ana Hategan, MD, FRCPC, Associate Clinical Professor, Department of Psychiatry and Behavioral Neurosciences, Division of Geriatric Psychiatry, McMaster University School of Medicine; Geriatric Psychiatrist, St Joseph's Health Care Hamilton, Canada

Disclosure: Book royalties and/or honoraria for articles from American Psychiatric Publishing, Springer, and Current Psychiatry.

Additional Contributors

Jennifer S Morse, MD, Associate Medical Director, Optum Health

Disclosure: Nothing to disclose.


Michael F Larson, DO Clinical Instructor, Department of Child and Adolescent Psychiatry, Harvard Medical School; Psychiatrist, Harvard Vanguard Medical Associates and Private Practice

Michael F Larson, DO is a member of the following medical societies: American Academy of Addiction Psychiatry, American Academy of Child and Adolescent Psychiatry, and American Society of Addiction Medicine

Disclosure: Nothing to disclose.


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