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.

Positional cloning and comprehensive mutation analysis of a Japanese family with lithium-responsive bipolar disorder identifies a novel DOCK5 mutation.

Bipolar disorder (BD) is a severe psychiatric disorder characterized by the recurrence of depressive and manic episodes. Its heritability is high, and many linkage and association studies have been performed. Although various linkage regions and candidate genes have been reported, few have shown sufficient reproducibility, and none have identified the pathogenic genes based on the results of the linkage analysis. To find functional variants that are expected to be rare and have strong genetic effects, we recruited ten healthy individuals, two individuals with unknown status, and six patients with BD or recurrent major depressive disorder (MDD) from a Japanese family consisting of 21 members. We performed a genome-wide linkage analysis using a 100K single-nucleotide polymorphism (SNP) array and microsatellite markers to narrow linkage regions within this family. Subsequently, we performed whole-exome sequencing for two patients with BD to identify genetic mutations in the narrowed linkage regions. Then, we performed co-segregation analysis for DNA variants obtained from the results of the exome sequencing. Finally, we identified a rare heterozygous mutation in exon 31 of DOCK5 (c.3170A>G, p.E1057G). Convergent functional genomics analysis revealed that DOCK5 was listed as one of the biomarkers for mood state and suicidality. Although DOCK5 is still a functionally unknown gene, our findings highlight the possibility of a pathological relationship between BD and DOCK5.

[Differences by sex and income level in mortality from causes directly related to alcohol in Navarre, 1993-2017]. / Diferencias por sexo y nivel de renta en la mortalidad por causas directamente relacionadas con el alcohol en Navarra, 1993-2017.

BACKGROUND: Alcohol consumption is a risk factor for many health problems. Mortality from causes of death wholly attributable to alcohol consumption by sex and income level was studied and trends in the 1993-2017 period were analyzed in Navarre (Spain). METHODS: Deaths due to alcohol-induced mental disorders, dependence and abuse, alcoholic cardiomyopathy, alcoholic cirrhosis and other alcoholic liver diseases, and accidental alcohol poisoning were selected through codes ICD-9 and ICD-10. Annual income that determines copayment level was used as an indicator of socioeconomic status. Mortality rates adjusted to the European standard population were calculated using the direct method and joinpoint regression was used to evaluate the temporal trend. RESULTS: A total of 441 deaths were recorded in the population aged 35-79 years. It highlights liver cirrhosis as the most common cause (77,5%). Death rates in men were ten and five times higher than in women in 1993-1997 and 2013-2017 periods, respectively. Compared to men with incomes above 18,000 €, mortality rates were five times higher in the population with incomes below 18,000 €. No statistically significant changes were observed in the trend of mortality rates throughout the period studied. CONCLUSIONS: Mortality by causes of death wholly attributable to alcohol has not decreased in Navarre in the last three decades, it is higher in men than in women and in the population with lower incomes.

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.

Healthcare Utilisation, Morbidities and Alcohol Use Monitoring Prior to Alcoholic Psychosis Diagnosis.

AIMS: The aim of this study was to describe healthcare utilisation, morbidities and monitoring of alcohol use in patients prior to a diagnosis of alcoholic psychosis in order to inform the early identification of patients at risk. METHODS: Using linked general practice and hospitalisation data in England (April 1997 to June 2014), we identified 1731 individuals (≥18 years) with a clinical recorded diagnosis of alcoholic psychosis and 17,310 matched controls without the disorder, we examined all prior general practitioner (family doctor) visits, hospitalisations, medically recorded morbidities and alcohol assessment/interventions records. Poisson regression models were used to compare rates of healthcare utilisation in people with alcoholic psychosis to those without. Logistic regression models were used to evaluate the association between alcoholic psychosis and prior morbidities. RESULTS: Patients with alcoholic psychosis showed increased levels of healthcare utilisation at least 5 years prior to their diagnosis. The most common reasons for prior healthcare visits were seizures and injuries and there was >4-fold higher rate of seizures, unintentional injuries and self-harm incidents among these patients up to 10 years prior to diagnosis, compared to the control population. A high proportion (78%) of patients had their alcohol consumption recorded, 50% had a record of heavy drinking but only one in five had any evidence of receiving an alcohol-related intervention. CONCLUSION: Patients present more often with seizures and injuries than the general population several years prior to a diagnosis of alcoholic psychosis. These visits represent opportunities for preventive action and imply that we may be missing opportunities to intervene.

You're the Flight Surgeon.

Levy B. You're the flight surgeon: alcohol-induced psychosis. Aerosp Med Hum Perform. 2018; 89(10):933-935.

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.

[Modeling of an influence of indicators of social stress on demographic processes in regions of the Russian Federation]. / Modelirovanie vliianiia indikatorov sotsial'nogo stressa na demograficheskie protsessy v regionakh Rossiiskoi Federatsii.

AIM: To assess an impact of indicators of social stress on demographic processes in regions of the Russian Federation using statistical methods. MATERIAL AND METHODS: The data of Rosstat «Regions of Russia¼ and «Health care in Russia¼ were used as information base. Indicators of about 80 subjects of the Russian Federation (without autonomous areas) for the ten-year period (2005-2014) have been created in the form of the database consisting of the following blocks: medico-demographic situation, level of economic development of the territory and wellbeing of the population, development of social infrastructure, ecological and climatic conditions, scientific researches and innovations. In total, there were about 70 indicators. Panel data for 80 regions of Russia in 10 years, which combine both indicators of spatial type (cross-section data), and information on temporary ranks (time-series data), were used. Various models of regression according to the panel data have been realized: the integrated model of regression (pooled model), regression model with the fixed effects (fixed effect model), regression model with random effects (random effect model). RESULTS AND CONCLUSION: Main demographic indicators (life expectancy, birth rate, mortality from the external reasons) are to a great extent connected with socio-economic factors. Social tension (social stress) caused by transition to market economy plays an important role. The integral assessment of the impact of the average per capita monetary income, incidence of alcoholism and alcoholic psychoses, criminality, sales volume of alcoholic beverages per capita and marriage relations on demographic indicators is presented. Results of modeling allow to define the priority directions in the field of development of mental health and psychotherapeutic services in the regions of the Russian Federation.

Preclinical voluntary drinking models for alcohol abstinence-induced affective disturbances in mice.

Negative reinforcement is widely thought to play an important role in chronic alcohol-use disorders (AUDs), and high comorbidity between AUDs and affective disorders highlights the importance of investigating this relationship. Prominent models posit that repeated cycles of alcohol (ethanol, EtOH) exposure and withdrawal produce circuit adaptations in the central nervous system that drive a transition from positive- to negative reinforcement-based alcohol seeking. Evidence supporting this theory has accumulated in large part using forced EtOH administration models, such as chronic intragastric gavage and chronic vapor inhalation. However, recent studies utilizing simple voluntary EtOH delivery systems show that forced abstinence from EtOH intake administered by the animal itself can produce evolving and significant affective disturbances, particularly in female C57BL/6J mice. Here, we highlight these recent studies to support the idea that voluntary EtOH administration in mouse models, as well as a protracted abstinence period and less commonly used behavioral tasks, could unveil affective disturbances during abstinence that have remained elusive using high dosage forced EtOH administration paradigms.

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.

Effects of alcohol on the offender's sanity-Issues of criminal law and psychiatry in light of findings of research.

The present report is the result of research on the causes of insanity or issuing opinions about the causes of insanity or diminished sanity perpetrators in criminal proceedings conducted in Poland (CEE). Research has shown the impact that has, in fact, use or abuse of alcohol and other alcoholic diseases on the status of the accused in criminal proceedings. This publication presents not only the results but also the basic regulations - valid in Poland and in other European countries - with respect to the responsibility of the perpetrators insane, with diminished sanity and being in a state of inebriation at the time of committing a criminal act.

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.

[Incidence of alcoholic psychoses, mortality from alcoholic poisonings and diseases of the liver and in Russia].

Authors studied the influence of availability of beer on mortality from alcoholic poisonings, diseases of a liver and incidence of alcoholic psychoses in Russia during 1995-2011. Time series analysis was performed using the method of ARIMA. There were no significant associations between the availability of beer and levels of mortality and morbidity.

Prevalence and Risk Factors of Violence by Psychiatric Acute Inpatients: A Systematic Review and Meta-Analysis.

BACKGROUND: Violence in acute psychiatric wards affects the safety of other patients and the effectiveness of treatment. However, there is a wide variation in reported rates of violence in acute psychiatric wards. OBJECTIVES: To use meta-analysis to estimate the pooled rate of violence in published studies, and examine the characteristics of the participants, and aspects of the studies themselves that might explain the variation in the reported rates of violence (moderators). METHOD: Systematic meta-analysis of studies published between January 1995 and December 2014, which reported rates of violence in acute psychiatric wards of general or psychiatric hospitals in high-income countries. RESULTS: Of the 23,972 inpatients described in 35 studies, the pooled proportion of patients who committed at least one act of violence was 17% (95% confidence interval (CI) 14-20%). Studies with higher proportions of male patients, involuntary patients, patients with schizophrenia and patients with alcohol use disorder reported higher rates of inpatient violence. CONCLUSION: The findings of this study suggest that almost 1 in 5 patients admitted to acute psychiatric units may commit an act of violence. Factors associated with levels of violence in psychiatric units are similar to factors that are associated with violence among individual patients (male gender, diagnosis of schizophrenia, substance use and lifetime history of violence).

[Alcohol-induced psychotic disorder: a systematic literature review]. / Psychotische stoornis door alcohol: een systematisch literatuuroverzicht.

BACKGROUND: From the second half of the 19th century eminent psychiatrists began referring to alcohol-induced psychotic disorder (AIPD) as a specific alcoholic psychosis. Over the last decades interest in AIPD seems to have declined: the last review dates form 1989. AIM: To review the recent literature on AIPD, revive interest in the disorder, evaluate the current scientific evidence and assess its clinical value. METHOD: We performed a Medline search based on the following terms: 'Psychoses, Alcoholic' [Mesh] OR 'alcohol induced psychotic disorder' OR 'alcoholic hallucinosis' OR 'alcohol hallucinosis'. Our search was restricted to articles written in English or Dutch and published between 1-1-1988 and 31-1-2013. RESULTS: We found 164 papers, from which we selected 21 for further discussion. The quality of the papers selected was variable, most of the papers being the result of clinical research. The most important findings referred to epidemiology: 0.4% lifetime prevalence in the general population, 4.0% in patients with alcohol dependence. We found only limited evidence of psychopathological differentiation between delirium and primary psychotic disorder. Correct diagnosis of AIPD is important because of the implications regarding the length and nature of the treatment: short or long course of antipsychotics, referral to a substance-abuse unit. CONCLUSION: AIPD has survived as a clinical entity. However, scientific evidence of this is limited. Further research is needed because it is vitally important that the patient receives the most appropriate treatment.