Alcohol-Related Psychosis

Etiology

A positive association between non-thought disorder psychiatric diagnoses (eg, ADHD, PTSD, anxiety disorders, major depressive disorders) and alcohol use, particularly with at-risk alcohol use or alcohol use disorder, has been strongly demonstrated in studies.[6] The association between alcohol use and disorders of thought (eg, schizophrenia, alcohol-induced psychiatric disorder) will be reviewed here. Please see StatPearls' companion resource, "Alcohol Withdrawal Syndrome," for further information on other alcohol withdrawal conditions, eg, delirium tremens and Wernicke-Korsakoff syndrome.

The etiology of the associated psychiatric disorder depends on the condition at hand. However, the interplay between existing psychiatric disorders or the consequent development of a psychiatric diagnosis outside of a traditional withdrawal syndrome is less understood.[6] While conditions, eg, Wernicke-Korsakoff syndrome, are well understood to be a result of thiamine deficiency and associated glucose metabolism derangements with resultant neurologic and psychiatric aberrations [7], ARP is less well understood, with a variety of hypotheses to describe the etiology of ARP. While dopamine, serotonin, and glutamate neurotransmission appear to be involved, the complexities surrounding this condition, including how ARP develops, individuals at risk, and the pathophysiology of psychosis, are still being unraveled.

Epidemiology

Alcohol use and misuse are common. According to the 2023 US National Survey on Drug Use and Health, 134.7 million alcohol users 12 years of age or older, 61.4 million people engaged in binge drinking in the past month, and 28.9 million people who had an alcohol use disorder in the past year were reported.[2023 National Survey on Drug Use and Health] While ARP is well established, this disorder appears to be relatively rare, with the lifetime risk of developing ARP among patients with alcohol dependence estimated to be 0.4% to 4%.[8][9] Other studies evaluating patients admitted to a hospital for alcohol dependence had an estimated prevalence of 0.4% to 4% but were as high as 12.4% in a study from Nepal.[10][8][2] 

A 2015 Dutch literature review on ARP disorders found a 0.4% lifetime prevalence in the general population and a 4% prevalence in patients with alcohol dependence.[11] A 2019 study found the prevalence of alcoholic hallucinosis was 0.9% in hospitalized patients with alcohol dependence.[12] Furthermore, in a study of 643 patients, the prevalence of acute alcoholic hallucinosis in hospitalized patients with alcohol dependence was 7.5%.[13] An older study found that among patients with alcohol dependence, only 2% to 3% had psychiatric symptoms [2], and only an estimated 33% of these patients had ARP, with the remainder primarily associated with alcohol withdrawal delirium.[9]

A significant overlap among patients with psychiatric disorders and alcohol use disorder (AUD) exists, with one meta-analysis finding a lifetime prevalence of 21%, with 10% having current AUD.[14] The World Health Organization’s World Mental Health Survey found the prevalence of lifetime AUD in people with psychiatric experiences to be 17% compared with 7.2% of people without a psychiatric diagnosis.[15] The risk of conversion from alcohol use with alcohol-induced psychosis to schizophrenia is 22% of the population with a hazard ratio of 74 (95%CI 48.4-113.3), second only to cannabis use.[16]

ARP was notably more prevalent among monozygotic twins (32%) than dizygotic twins (13%). However, no significant difference was observed in the prevalence of schizophrenia or alcoholism among the co-twins of index twins, regardless of whether the index twin had a diagnosis of alcoholic psychosis.[17] These findings indicate that individuals with alcoholism and schizophrenia may have separate underlying predispositions. Collectively, the available evidence does not support a genetic association between schizophrenia and ARP. Instead, it suggests that specific individuals with alcoholism may have an increased susceptibility to the psychotogenic effects of alcohol, reinforcing the concept of ARP as a distinct and independent disorder. Overall, the evidence does not support a genetic link with schizophrenia in patients with ARP.[2]

Pathophysiology

The pathophysiology of ARP is complex and not fully understood. However, it involves numerous neurotransmitters, including dopamine, serotonin, gamma-aminobutyric acid (GABA), and glutamate.

Dopamine Neurotransmitter Effects of Alcohol

Studies have demonstrated that alcohol administered to rats will increase the release of dopamine in the nigrostriatal and mesolimbic tracts.[18] Additionally, an indirect marker of dopamine activity, homovanillic acid, is elevated in the cerebrospinal fluid of individuals with auditory and visual hallucinations occurring as part of alcohol withdrawal.[19]

Serotonin Neurotransmitters Effects of Alcohol

Serotonergic drugs, eg, d-lysergic acid diethylamide, are known to cause hallucinations.[20] While alcohol is not directly serotonergic, it does have effects on the serotonin system. In primates, an increase in 5-HT1A serotonin receptor binding is observed during chronic alcohol self-administration but was independent of the amount of alcohol consumed.[21] Additionally, in humans, the concentration of serotonin transporters was up to 35% less in the perigenual region of the cerebral cortex in patients with alcohol use disorder than it was in patients without alcohol use disorder, effectively causing a serotonin reuptake scenario.[22]

Gamma-Aminobutyric Acid and Glutamate Neurotransmitters Effects of Alcohol

Chronic alcohol use is also well known to cause decreased GABA-receptor concentration and inhibitory tone while at the same time increasing neuroexcitatory tone due to the direct effect of alcohol. Evidence demonstrates that patients with alcohol hallucinosis have increased concentrations of serum glutamate and aspartate, indicating that this imbalance and overexcitation may play a role in the development of hallucinations.[4] Experts have also theorized that aromatic beta-carboline compounds may be implicated in the pathogenesis of hallucinations. These compounds, when consumed as a plant extract, can cause hallucinations. One study determined that 2 compounds (norharman and harman) were significantly elevated in alcoholic patients compared with nonalcoholic patients. In a subgroup of individuals who were diagnosed with hallucinosis, the levels slightly rose over the 3-week detoxification period, while it dropped somewhat for those individuals without hallucinosis. However, this was not a statistically significant trend.[23] However, another study several years later demonstrated that tobacco use was a confounder.[24]

Directly Toxic Effects of Alcohol

Lastly, the direct toxic effects of alcohol on the auditory system and other regions of the brain may also be contributory [25]; positron emission tomography has suggested an association with thalamic dysfunction.[26] However, these findings were associated with glucose metabolism issues, which were resolved in follow-up studies. Therefore, thiamine deficiency, or the deleterious effects of alcohol on glucose metabolism, may be responsible instead of structural damage.[27]

History and Physical

As with any form of psychosis, patients with ARP may present with a wide range of symptoms. A detailed history is the key to differentiating ARP from other psychoses or alcohol withdrawal syndromes. The greater the consumption of alcohol, the greater the risk of developing ARP.[28][13] Most cases of ARP develop within 2 days of the cessation of alcohol and typically develop gradually.[29] Unlike delirium tremens, which require a longer duration of binging, the duration of consumption of alcohol preceding ARP may be shorter, potentially with increasing frequency as the binging continues.[4]

Alcohol-Related Psychosis Diagnostic and Statistical Manual of Mental Disorders Diagnostic Criteria

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria require (A) the presence of one or both of the following symptoms: delusions and hallucinations, with (B) evidence from the history and physical examination or laboratory findings that either the symptoms developed within or during a month of alcohol intoxication or withdrawal or medication used is etiologically related to the disturbance; the symptoms are (C) not better accounted for by a psychotic disorder that is not substance-induced (eg, symptoms precede substance use); (D) the disturbance does not exclusively occur during delirium; and (E) the disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Verbal hallucinations are the most common type of hallucination, heard in the background and not directed at the patient. However, this is not always true; sometimes, the voices are direct or concern the patient, but this is truer for advanced disease. However, the words may be about the patient typically in a negative tone, and they are hearing them in the third person as an involuntary participant.[30] Commonly, only 1, or possibly 2, voices are heard, with the repetition of a simple phrase. Verbal hallucinations are commonly associated with 4 themes:

• Stalking the patient to destroy him physically
• Alcohol use disorder
• Immoral behavior
• The patient's sexual relationships [4] 

In more advanced stages, verbal hallucinations are more commonly also associated with delusions. In addition to verbal hallucinations, visual and rarely tactile hallucinations may also be present.[30] If hallucinations persist for longer than 1 to 2 weeks, the patient is at an increased risk of developing chronic hallucinations.[4] 

One of ARP's most critical historical features is a clear sensorium, which helps differentiate it from delirium tremens and other psychoses.[9] In comparison to delirium tremens, delirium associated with ARP is typically related to hallucinations, while this is not the norm with delirium tremens. The hallucinations associated with delirium tremens tend to be more visual than those of ARP, and patients tend to be older and have a more extended history of alcohol use disorder.[3] Depressed mood and suicidal thoughts are common in both groups.[9]

Additional Clinical Assessments

Additionally, assessing socioeconomic risk factors is vital since individuals diagnosed with schizophrenia and alcohol use disorder are frequently exposed to factors that heighten their risk for excessive alcohol consumption, thereby increasing their likelihood of developing the disorder. These factors include lower educational attainment, homelessness, and a history of childhood conduct problems.[31] However, these factors are common to individuals who develop ARP, likely because the psychopathology of alcohol hallucinosis closely resembles paranoid schizophrenia.[32]

Evaluation

Diagnosing ARP requires a complete clinical assessment, as no specific laboratory or imaging tests can definitively confirm the condition. The primary goal of evaluation is to identify alternative causes of psychosis, assess withdrawal severity, and rule out medical conditions that could be contributing to the patient’s symptoms. This includes evaluating for critical electrolyte imbalances, vitamin deficiencies (eg, thiamine deficiency), hypo- or hyperglycemia, infections, electro cardiac abnormalities, intracranial pathology, trauma, or signs of toxidromes. Other potential causes of altered mental status, such as liver disease, metabolic derangements, and sepsis, should also be considered.[33] Additionally, recognizing dual diagnoses and not assuming that alcohol is the sole cause of the patient’s hallucinations is essential.[34]

Clinical Assessment 

A thorough history and physical examination are the foundation of ARP diagnosis. Key aspects to assess include:

• Substance use history: Obtain detailed information about alcohol consumption patterns, including type, quantity, frequency, duration, and prior withdrawal symptoms. Additionally, assess for illicit drug use, adverse effects, previous cessation attempts, prior treatment programs, and use of medications for remission.
• Psychiatric evaluation: Review any history of psychiatric disorders, prior hospitalizations, medications, and treatment responses. Determining whether psychotic symptoms predate alcohol use, which may suggest an underlying primary psychotic disorder, is crucial.
• Medical history and medication use: Evaluate for comorbid medical conditions, as well as the use of prescribed, over-the-counter, and illicit substances that may contribute to psychosis or withdrawal symptoms.
• Physical examination: Assess the airway, breathing, circulation, and neurological status. Special attention should be given to general appearance (unkempt, flat affect, alcohol odor, and response to internal stimuli) and signs of trauma, particularly head injuries.

Diagnostic and Statistical Manual of Mental Disorders Diagnostic Criteria

The DSM-5 classifies substance-induced psychotic disorder as the presence of hallucinations or delusions that develop during or shortly after substance intoxication or withdrawal. A primary psychotic disorder must not better explain symptoms, must not occur exclusively during delirium, and must cause clinically significant distress or impairment.

The DSM-5 criteria for AUD can help assess the severity of alcohol dependence and the risk for withdrawal. A diagnosis of AUD is made if a patient exhibits at least 2 of the following DSM-5 criteria within 12 months:

• Alcohol is consumed in larger amounts or over a longer period than intended
• Persistent desire or unsuccessful efforts to cut down or control alcohol use
• A significant amount of time spent obtaining, using, or recovering from alcohol
• Craving or a strong urge to drink alcohol
• Recurrent alcohol use leading to failure in fulfilling major obligations (work, school, home)
• Continued alcohol use despite social or interpersonal problems
• Giving up or reducing important social, occupational, or recreational activities due to alcohol use
• Recurrent alcohol use in physically hazardous situations
• Continued alcohol use despite knowing it worsens a physical or psychological condition
• Tolerance, requiring increased amounts for the same effect or reduced effect from the same amount
• Withdrawal, with characteristic symptoms, or using alcohol to relieve withdrawal symptoms

The severity of substance-induced psychotic disorder can be determined using the following classification:

• Mild: presence of 2 to 3 symptoms
• Moderate: presence of 4 to 5 symptoms
• Severe: presence of 6 or more symptoms

Assessment of Withdrawal Severity

The Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA-Ar) is a validated tool used to assess withdrawal severity and guide management. This 10-item scale evaluates symptoms, including nausea, tremors, sweating, anxiety, agitation, hallucinations (visual, auditory, tactile), headache, and orientation, using the following scoring system:

• Score of ≤10: Mild withdrawal (may not require medication)
• Score of 11 to 15: Moderate withdrawal (close monitoring and possible benzodiazepine treatment)
• Score of ≥16: Severe withdrawal (high risk of seizures, delirium tremens, and complications requiring aggressive treatment)

Regular CIWA-Ar monitoring is essential to ensure appropriate treatment and prevent complications.[MDCalc CIWA-Ar Assessment Tool]

Diagnostic Studies

While no test confirms ARP, ancillary testing is necessary to exclude alternative diagnoses.

Laboratory tests

Laboratory studies that should be performed include:

• Complete blood count (CBC)
• Comprehensive metabolic panel (CMP)
• Liver function tests (LFTs)
• Ammonia levels (to assess hepatic encephalopathy)
• Toxicology screening (serum and urine drug testing)

Imaging studies

Imaging studies that should be considered based on clinical indications include:

• Computed tomography of the brain to evaluate for trauma, hemorrhage, stroke, or space-occupying lesions.
• Magnetic resonance imaging of the brain in cases of persistent symptoms or suspected Wernicke-Korsakoff syndrome.

Differentiating ARP from Schizophrenia 

Distinguishing ARP from primary psychotic disorders, such as schizophrenia, is critical. While both conditions may present with hallucinations and delusions, ARP typically has the following characteristics:

• Develops in the context of recent alcohol use or withdrawal
• Resolves with sustained abstinence
• Occurs at an older age than schizophrenia
• Presents with more depressive and anxiety symptoms rather than disorganized or negative symptoms
• Is associated with greater insight and better judgment [35][36][37]

In contrast, schizophrenia is usually associated with the following clinical features:

• Earlier onset earlier (late adolescence to early adulthood)
• Persists independent of substance use
• Features more negative symptoms (apathy, social withdrawal, blunted affect)
• Involves more chronic functional impairment

No family history of schizophrenia and a clear history of alcohol use leading to symptoms support the diagnosis of ARP rather than primary psychosis.

Treatment / Management

The main priority during the treatment of ARP is to stabilize the patient, paying close attention to the airway, breathing, and vital signs. If the patient requires sedation due to ARP, neuroleptics (eg, haloperidol) have been considered the first-line medications for treatment. Benzodiazepines (eg, lorazepam) are used if concern for alcohol withdrawal and seizures is present. Certain atypical antipsychotics, including ziprasidone and olanzapine, have also been used to treat patients with acute psychosis.

Some patients may require the use of physical restraints to protect the patient as well as the staff. Patients with ARP, which is associated with higher rates of suicidal behaviors, must also be evaluated for suicidal thoughts. The prognosis for ARP is less favorable than earlier studies had speculated. However, if the patient can abstain from alcohol, the prognosis is good. If patients are unable to abstain from alcohol, the risk of recurrence is high.[38][39][40]

Differential Diagnosis

Differential diagnoses of ARP include:

• Bipolar disorder type 1
• Cannabis-related disorders
• Cocaine-related psychiatric disorders
• Delirium
• Delirium tremens
• Hallucinogen use
• Major disruptive disorder, single or recurrent, with severe psychotic features
• Schizophrenia
• Stimulant use
• Wernicke-Korsakoff syndrome

Prognosis

Abstinence will usually lead to cessation of ARP [41]; however, hallucinations may persist in some patients.[2] Whether this is from another underlying psychiatric disorder or persistent symptoms of ARP is unclear. However, frequent relapses portend a worse outcome, with 5% to 30% of cases developing a schizophrenia-like condition.[2] However, the liberal use of antipsychotics today may affect the persistence of symptoms, which have changed over the past 50 years.[2]

Mortality for patients with ARP is high, with one study finding an 8-year mortality of 37% with an age- and gender-adjusted hazard ratio of 20 compared with the rest of the population and 12 compared with alcohol-dependent participants without ARP.[8] Notably, this sample size was small, with 39 participants total and 31 with an alcohol-induced psychiatric disorder of any type. Mortality for patients with alcohol use disorder is high, with a 4-fold (RR = 3.94, 95% CI = 3.53-4.40) risk of death compared with current non-drinkers and a mortality rate of 3.13 (95% CI = 1.07-9.13) per 1000 person-years.[42]

Interpretation of earlier studies requires caution, as follow-up cohorts often included individuals with other psychiatric diagnoses, such as mood disorders, including bipolar disorder, schizophrenia, delirium tremens, personality disorders, and drug addiction. Additionally, evolving diagnostic criteria and more nuanced definitions have made older studies less applicable to current understanding.

Complications

Complications of ARP include:

• Depression
• Suicide
• Major psychosocial impairment
• Development of persistent hallucinations
• Development of schizophrenia-like condition