Acute Alcoholic Hallucinosis: A Review.

Acute alcoholic hallucinosis is a psychotic disorder characterized by a predominance of auditory hallucinations with delusions and affective symptoms in the clinical picture. Classically, it develops as part of the alcohol withdrawal syndrome. The prevalence of acute alcoholic hallucinosis ranks second among alcohol-related psychoses after alcohol delirium. The study aimed to systematize the scientific data on the history of alcoholic hallucinosis, its pathogenesis, clinical presentation, and treatment approaches. A literature search was performed in PubMed, Scopus, Google Scholar, and eLibrary. The following words and combinations were used as search strings: (alcoholic hallucinosis OR alcoholic psychosis OR alcohol-related psychosis OR alcohol-induced psychosis OR alcohol-induced psychotic disorder OR complicated alcohol withdrawal syndrome) NOT (animal OR rat OR mouse). The relevant information concerning the history of acute alcoholic hallucinosis, its pathogenesis, clinical picture, and treatment approaches was systematized and summarized. This review presents relevant findings regarding acute alcoholic hallucinosis. Limitations of the review include the use of heterogeneous and mostly descriptive studies and studies on small cohorts of patients.

Association of CYP2D6*4 Polymorphism with the Steady-State Concentration of Haloperidol in Patients with Alcohol-Induced Psychotic Disorders.

Background: CYP2D6 subfamily isoenzymes play an important role in the biotransformation of haloperidol, and their activity may influence the efficacy and safety of haloperidol. The use of haloperidol is often associated with the occurrence of adverse drug reactions (ADRs), such as dyskinesia, acute dystonia, and orthostatic hypotension. Previous studies have demonstrated the relationship between the CYP2D6*4 genetic polymorphism and CYP2D6 activity, as well as haloperidol efficacy and safety rates. Purpose: To evaluate the association of CYP2D6*4 genetic polymorphism with the steady-state concentration of haloperidol in patients with acute alcohol-induced psychotic disorders (AIPDs). Material and methods: The study involved 100 male patients with AIPD (average age 41.4 ± 14.4 years) who received haloperidol by injections in a dose of 5-10 mg/day. The efficacy profile was assessed using a validated psychometric PANSS scale (Positive and Negative Syndrome Scale). Therapy safety was assessed using the internationally validated UKU (Side-Effect Rating Scale) and SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scales. Genotyping was performed with the real-time polymerase chain reaction. Results: We revealed the statistically significant results in terms of therapy safety evaluation (dynamics of the UKU scores: (GG) 8.00 [7.00; 10.00], (GA) 15.0 [9.25; 18.0], p < 0.001; dynamics of the SAS scores: (GG) 11.0 [9.0; 14.0], (GA) 14.50 [12.0; 18.0], p < 0.001. Pharmacokinetic study showed a statistically significant difference across the groups with different genotypes: (GG) 3.13 [2.32; 3.95], (GA) 3.89 [2.92; 5.26], p = 0.010. Conclusion: It can be concluded that patients with the GA genotype have a higher risk of ADRs compared to patients who carry the GG genotype. It was shown that CYP2D6*4 genetic polymorphism has a statistically significant effect on the steady-state concentration of haloperidol.

Phenomenology and Course of Alcoholic Hallucinosis.

Objective: The objective of the study was to examine the correlates, phenomenology, and short-term treatment response to benzodiazepines and antipsychotics in an inpatient sample with alcohol-induced psychotic disorder, predominant hallucinations i.e., F10.52. Methods: We reviewed the charts of the patients admitted in a tertiary care addiction treatment center between 2010 and 2016 with the diagnosis of alcoholic hallucinosis. Results: Among 6,493 patients admitted with alcohol dependence during the study period, 61 patients (0.9%) had alcoholic hallucinosis. Among them, 41 (67.2%) had alcoholic hallucinosis in the past; 26 (42.6%) had a family history of psychosis. Only auditory hallucinations were found in 46 patients (75.4%), only visual hallucinations in 3 patients (5%), and both auditory and visual hallucinations in 12 (19.7%). Thirty-four (55.7%) had delusions, which were secondary to hallucinations. Suicidality which includes suicidal ideas and attempts was noted in 12 (19.7%) patients. Fifty-three (86.9%) patients had hallucinations exclusively during alcohol withdrawal, while 8 (13.1%) had them during withdrawal as well as while consuming alcohol. At the end of six months, 13.1% of the patients had an independent psychotic disorder diagnosed. The primary mode of management was treatment with only benzodiazepines (n = 37, 60.7%) or benzodiazepines and antipsychotics (n = 24, 39.3%). The reasons for starting antipsychotics were the presence of florid psychotic symptoms (26.2%) and incomplete symptom resolution with benzodiazepines (9.8%). The median duration of response was four days, with 25th to 75th quartile range at two to seven days. Conclusions: Alcoholic hallucinosis is an acute short-lasting psychotic disorder which lasts for less than a week when treated. Suicidality is high in this group, which needs attention. Benzodiazepines as part of withdrawal management may be sufficient for a majority of cases. Antipsychotics may be required in selected cases. A high degree of recurrence and morbidity indicates a need to intervene early with an abstinence-oriented management goal.

Treatment of Alcohol-Induced Psychotic Disorder (Alcoholic Hallucinosis)-A Systematic Review.

AIMS: To evaluate the effectiveness of evidence based treatments for alcohol-induced psychotic disorder (AIPD) as described by ICD-10 and DSM-5, a condition that is distinct from schizophrenia and has a close relationship with alcohol withdrawal states. METHOD: Systematic review using PRISMA guidelines. RESULTS: Of 6205 abstracts found, fifteen studies and ten case reports met criteria and were examined. Larger studies examined the use of first-generation antipsychotic drugs, reporting full or partial remission in most patients. Newer case reports report similar results using second generation antipsychotic drugs. Novel treatments, such as those acting on GABA receptors reported low numbers of patients in remission. Some large studies report the successful use of standard alcohol withdrawal treatments. CONCLUSION: The findings of our systematic review are inconclusive. There was significant heterogeneity between and within studies. Significant publication bias is likely. Randomized control trials of more carefully delineated samples would produce evidence of greater clinical utility, for example, on differential effectiveness of antipsychotics and optimal length of standard alcohol withdrawal treatments. AIPD patients who show poor treatment responses should be studied in greater depth. SHORT SUMMARY: This systematic review of alcohol-induced psychotic disorder treatment found 15 studies and 10 case reports of relevance. Older studies of first-generation antipsychotics reported full or partial remission in most patients, as did newer studies with second-generation antipsychotics. Novel drugs reported low remission rates. Standard alcohol withdrawal treatments were successful.

Genotyping and phenotyping of CYP2D6 and CYP3A isoenzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration.

BACKGROUND: Haloperidol is used for the treatment of alcohol use disorders in patients with signs of alcohol-related psychosis. Haloperidol therapy poses a high risk of adverse drug reactions (ADR). Contradictory data, which include the effects of genetic polymorphisms in genes encoding the elements of haloperidol biotransformation system on haloperidol metabolism rate and plasma drug concentration ratio, are described in patients with different genotypes. The primary objective of this study was to investigate the effects of CYP2D6 and CYP3A5 genetic polymorphisms on haloperidol equilibrium concentration in patients with alcohol use disorder. METHODS: The study included 69 male patients with alcohol use disorder. Genotyping was performed using the allele-specific real-time PCR. CYP2D6 and CYP3A were phenotyped with HPLC-MS using the concentration of endogenous substrate of the enzyme and its urinary metabolites [6-hydroxy-1,2,3,4-tetrahydro-ß-carboline(6-HO-THBC) to pinoline ratio for CYP2D6 and 6-ß-hydroxycortisol to cortisol ratio for CYP3A]. The equilibrium plasma concentration was determined using LC-MS-MS. RESULTS: Results indicated that both C/D indexes and equilibrium concentration levels depend on CYP2D6 genetic polymorphism, but only in patients receiving haloperidol intramuscular injections [0.26 (0.09; 0.48) vs. 0.54 (0.44; 0.74), p=0.037]. CONCLUSIONS: The study demonstrates that CYP2D6 genetic polymorphism (1846G>A) can affect haloperidol concentration levels in patients with alcohol use disorder.

Marchiafava-Bignami Disease with frontal cortex involvement and late onset, long-lasting psychiatric symptoms: a case report.

AIMS: To describe the case and management of a patient with Marchiafava-Bignami Disease (MBD) with frontal cortical lesions, no specific symptom at first referral to the Emergency Room, and late onset of atypical psychiatric symptoms. METHODS: We report the case of a 44-year-old patient with a history of chronic alcohol abuse, eventually diagnosed with MBD. RESULTS: Magnetic Resonance showed lesions in the splenium and the body of corpus callosum and bilateral lesions of the frontal cortex. The patient showed late-onset atypical psychiatric symptoms which were drug resistant. DISCUSSION: The case we describe seems to support the existing few ones describing cortical involvement in MBD, which suggest that this is associated with a poorer prognosis. Psychiatric symptoms may be challenging to treat because of drug resistance. CONCLUSIONS: The involvement of psychiatrists together with neurologists and radiologists, with a consultation-liaison approach proved important for the achievement of diagnosis and of the most appropriate management and treatment for this patient.

A Simplified Protocol for the Treatment of Alcohol Withdrawal.

OBJECTIVES: The aim of the study was to evaluate a novel simplified tool for symptom-triggered treatment of alcohol withdrawal. METHODS: This retrospective cohort study involved inpatients in a county hospital with an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis of alcohol withdrawal syndrome (AWS) or delirium tremens between January 1, 2007 and December 31, 2008. The study used the Highland Alcohol Withdrawal Protocol (HAWP)-a simplified derivative of the Revised Clinical Institute Withdrawal Assessment for Alcohol. Multivariable regression analysis was performed to compare severity of withdrawal to hospital length of stay, total dose of sedative given, and risk of complications. RESULTS: The study identified 442 patients with a primary diagnosis of AWS or delirium tremens, and those with another primary medical diagnosis complicated by alcohol withdrawal. After adjusting for demographic variables, each one-point increase in the initial and maximum HAWP scores correlated with an increase in the hospital length of stay of 0.3 days [95% confidence interval (95% CI), 0.17 to 0.43 days] and 0.45 days (95% CI, 0.32-0.57 days), and a 15.8 mg (95% CI, 6.6-25.1 mg) and 19.8 mg (95% CI, 11.1-28.5 mg) increase in the total dose of lorazepam given, respectively. The complication rate of seizures, intubations, pneumonia, and death was 13.1%, 12.9%, 6.1% and 0.9%, respectively; a composite endpoint of these outcomes also correlated with initial and maximum HAWP scores (odds ratio 1.09, 95% CI, 1.03%-1.14%). CONCLUSIONS: The HAWP correlates with medication received and complications, and as such appears to give an indication of AWS severity. It is feasible and shorter than prior scales, and merits further study to confirm its effectiveness as part of symptom-triggered protocols to manage alcohol withdrawal in the hospital.

Alcohol-induced psychotic disorder: a review.

While alcohol-induced psychotic disorder (AIPD) is well recognised, relatively little is known about the condition. We undertook a review of the literature to identify studies on the epidemiology, clinical manifestations, underlying neurobiology and treatment of AIPD. Few prospective studies have been conducted on AIPD. Recent advances have focussed on epidemiological, phenomenological, neuro-imaging, treatment and outcome issues. Current evidence suggests AIPD can be clinically distinguished from alcohol-withdrawal delirium and schizophrenia. The disorder may be more common than previously recognised depending on the inclusion criteria applied. AIPD is associated with high co-morbidity with other psychiatric disorders, high re-hospitalization and mortality rates and suicidal behaviour. Concurrent dysregulation of several neurotransmitter systems may be involved in the pathogenesis of hallucinations in alcohol dependence, and neuro-imaging studies suggest perfusion abnormalities to various brain regions. Antipsychotic treatment remains the preferred treatment for AIPD. The prognosis appears less favourable than previously believed, yet usually good when abstinence can be maintained.

Alcohol-induced psychotic disorder: brain perfusion and psychopathology--before and after anti-psychotic treatment.

Alcohol-induced psychotic disorder (AIPD) also known as alcohol hallucinosis is a rare complication of alcohol abuse. The pathogenesis and treatment of AIPD are still unclear. Few prospective treatment studies are available but case reports generally suggest that anti-psychotic treatment is effective. Brain imaging changes in relation to treatment response have also not been studied except for case reports. The aim of this study was to investigate the effect of anti-psychotic treatment on psychopathology and regional cerebral blood flow (rCBF) in patients with AIPD before and after 6 weeks of treatment. Nineteen patients with AIPD were assessed by the Positive and Negative Syndrome Scale (PANSS) and single photon emission computed tomography (SPECT) before and after 6-weeks of open-label treatment with a fixed dose of haloperidol (5 mg/day). Highly significant improvements were noted on the positive, general and total scores of the PANSS. Post-treatment increased rCBF to the left caudate and left frontal lobe was noted. Changes in frontal, temporal, parietal, occipital, thalamic and cerebellar rCBF showed significant negative correlations with the degree of symptom improvement, suggesting dysfunction of these areas in AIPD. Psychopathological and rCBF findings suggest reversible generalised cerebral dysfunction in AIPD.

[Current peculiarities of alcoholic psychosis].

The follow-up study of alcoholic psychoses in male patients admitted to a clinical department of a psychiatric hospital in 2005-2007 was carried out. Patients with alcoholic psychoses made up from 15 to 30% of all patients. The number of psychosis had seasonal variations with the elevations in spring and autumn, peaks in January, lune and October. Alcoholic delirium morbidity made up from 69 to 82% of the total number of alcoholic psychoses, alcoholic hallucinosis varied from 14 to 27%. Other forms were presented by single cases. In alcoholic delirium hallucinations had brighter, sated character. The most specific were visual hallucinations in the form of zoohallucinations, hallucinations of an oral cavity ("sensation of threads, hair etc"). The most often observable characters were "extraneous people, animal, demons". In alcoholic hallucinosis, verbal contrast hallucinations, making comment hallucinations, visual illusions were most frequent. The family history of mental disorders and alcoholism was noted in 30% of patients with alcoholic psychosis. The probability of occurrence of alcoholic psychoses depended on the quality of consumed drinks. The presence of a cranial-brain injury in the anamnesis considerably aggravated the disease forecast and increased the risk of seizure syndrome.

Psicofarmacoterapia en el tratamiento de los trastornos relacionados con el alcohol / No disponible

El desarrollo de la neurociencia, particularmente el entendimiento del sistema neurotransmisor, ha llevado a una mayor utilización de los psicofármacos en el tratamiento del alcoholismo en los últimos veinte años. El particular interés de la compulsión o deseo ("craving") en el alcoholismo como la posible influencia negativa que es causa de la falta de habilidades para establecer la abstinencia, y la muy notable presencia de comorbilidad de la adicción al alcohol con otros trastornos mentales, abrió la posibilidad de aplicación de numerosos tratamientos psicofarmacológicos como posibilidades terapéuticas. Todos los conocimientos provenientes del campo de la psicoterapia y las actividades socio-terapéuticas por un lado, y la eficiencia de la medicación psicofarmacológica en el establecimiento y mantenimiento de la abstinencia durante el curso del tratamiento de la adicción por otro, han realzado las posibilidades de tratamientos de calidad y rehabilitación para pacientes adictos al alcohol

[The validation of the expediency of using pimozide in treating the hypomania syndrome of alcoholic origin]. / Obhruntuvannia dotsil'nosti zastosuvannia pimozydu v likuvanni hipomaniakal'noho syndromu alkohol'noho pokhozhdennia.

In a clinical and psychopathological study of alcohol-dependent patients presenting with emotional disturbances and hypomaniac syndrome, expediency was shown of use of a neuroleptic drug preparation pimozide in the treatment of hypomaniac syndrome of alcohol genesis.

[Thiamine treatment in psychiatry and neurology]. / Die Thiaminbehandlung in der Psychiatrie und Neurologie.

Every physician knows that alcohol dependence, alcohol withdrawal and Wernicke-Korsakow-syndrome require substitution with thiamine, in acute stages even parenterally. This would be trivial if there was not the widespread fear of anaphylactic, even lethal reactions to parenteral thiamine application. The present article reviews the literature published on thiamine since 1936, when the first synthetic, parenteral thiamine preparation became available, and, on this basis, tries to give practical advice and therapeutic regimens for the treatment of thiamine deficiency states. Controlled clinical studies on indications and differential thiamine therapy have not been published. From the data that are available, the following conclusions can be drawn: 1) Acute mortality of Wernicke-Korsakow-syndrome is about 20%. 2) Oral thiamine is safe. 3) The risk for an anaphylactic shock due to parenteral thiamine administration is below 1 to 100,000. 4) Not only alcohol but any condition with either increased metabolic need (pregnancy, consuming diseases) or deficient nutrition (including eating disorders) can lead to thiamine deficiency. Therefore, we suggest: 1) Oral thiamine substitution with at least 50 mg per day and supply of a sufficient and complete diet should be given to any person that might be at risk for thiamine deficiency. 2) Any patient suspicious for acute thiamine deficiency needs to be treated under inpatient conditions and there needs to receive 50 to 100 mg thiamine intravenously 3 to 4 times a day. 3) General practitioners, psychiatrists and neurologists should take care of the oral supplementation of thiamine, sufficient nutrition, and they are the physicians to diagnose early stages of thiamine deficiency.

Treatment of psychiatric aspects of alcohol misuse.

Psychiatric disorders and alcohol misuse often coexist. This article outlines the clinical management of these comorbid disorders. It discusses and suggests therapeutic recommendations.

[Alcohol-induced hallucinosis. Clinical aspects, pathophysiology and therapy]. / Die Alkoholhalluzinose. Klinik, Pathophysiologie und Therapie.

In recent years, little research has been focused on alcohol hallucinosis. The psychopathology of alcohol hallucinosis (vivid acoustic hallucinations, paranoid symptoms and fear) resembles paranoid schizophrenia, but other organic mental disorders have to be excluded too. Prognosis is usually good, but in 10-20% of cases alcohol hallucinosis tends to become chronic. Possible pathophysiological mechanisms involved in the development of the syndrome are changes in dopaminergic transmission or other neurotransmitter systems and neuronal membranes, elevated levels of betacarbolines and an impaired auditory system. For treatment, highly potent neuroleptics (haloperidol) are the drugs of first choice. In the case of alcohol abstinence the prognosis is good, but otherwise the risk of a recurrence is high.

Assessment of diazepam loading dose therapy of delirium tremens.

The efficacy of the diazepam loading dose method of treatment of delirium tremens was assessed in comparison with the traditional therapy. The experimental group and the control group comprised 51 and 45 patients respectively. The clinical institute withdrawal assessment for alcohol (CIWA-A) scale was applied to assess the intensity of the symptoms. Diazepam doses in the experimental group oscillated from 40 to 210 mg (mean 86.9 +/- 47.2 mg). The control group was receiving diazepam and other psychotropic drugs in divided doses. In the experimental group deliric symptoms were present from 2 to 24 h (mean 6.9 +/- 4.8 h), and in the control group from 2 to 123 h (mean 33.8 +/- 25.7 h). The results show a large efficacy of the loading dose method corresponding to substantial reduction of the psychosis duration (fivefold in comparison to the control group). The method proved to be safe, with no significant complications.