Pharmacotherapy of schizophrenia with comorbid substance use disorder--reviewing the evidence and clinical recommendations

Substance use disorder is the most common psychiatric comorbidity in schizophrenic patients, with prevalence rates of up to 65%. Recommendations for antipsychotic pharmacotherapy in schizophrenia are based on studies that excluded patients with this dual diagnosis. In the present comprehensive systematic review, the pharmacological studies performed in this subgroup of patients are summarised and discussed from the standpoint of evidence-based medicine. Unfortunately, randomized controlled studies, providing a high evidence level, in patients with this dual diagnosis are rare. Data, mainly based on open studies or case series, suggest superior efficacy for second generation antipsychotic agents (SGAs) (aripiprazole, clozapine, olanzapine, quetiapine, risperidone) with regard to improvement of distinct psychopathological symptoms, reduced craving and greater reduction of substance use compared with orally administered conventional antipsychotics (FGAs). Tricyclic antidepressants given adjunctive to antipsychotic maintenance therapy showed efficacy in reducing substance use and craving. The administration of anti-craving agents (naltrexone) led to a decrease of drug intake. Unfortunately, there is no clinical experience with acamprosate in schizophrenic patients with comorbid alcoholism. In conclusion, there are more theoretically based arguments for the preferential use of SGAs in schizophrenic patients with comorbid substance use disorder while the empirical evidence is weak. The early initiation of treatment with antidepressants, depending on the patient's psychopathology, as well as add-on medication with anti-craving agents should be considered.     

Gender-specific interactions between alcohol metabolism genes and severity of quantitative alcohol-related-traits in a Tibetan population

Association between genes influencing alcohol metabolism and alcohol use disorders (AUD) has been extensively studied, but the effect of interactions between these genes and AUD have rarely been tested. Our previous case–control study in a Tibetan population noted that the positive association between *c2 allele of cytochrome P4502E1 (CYP2E1) gene and AUD might only exist in males who are homozygotes for *1 alleles of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B) genes, but this interaction did not reach statistical significance. Using the same set of data, the present study was aimed at exploring interactions between these genes and quantitative alcohol-related-trait scores (QARTs), and whether these are influenced by gender. The sample included 383 AUD cases with the alcohol use disorders identification test (AUDIT) score ≥10 and 350 normal controls with the AUDIT score ≤5. QARTs were measured using three factors from AUDIT. Possible associations of QARTs with interactions among genotypes of ALDH2*1/*2, ADH1B*1/*2 and CYP2E1*c1/c2* and sex were analyzed in AUD cases and normal controls separately. The subjects with *2 alleles of ALDH2 or/and ADH1B had significantly lower scores of alcohol intake among controls but had significantly higher scores of alcohol related problems among cases. The score of alcohol intake in male cases who are homozygous for ALDH2*1 and ADH1B*1 and with CYP2E1*c2 allele was significantly higher than that of other cases. These findings suggest that interactions between genes influencing alcohol metabolism are influenced by gender and might affect QARTs differently between the milder-/non-drinkers and AUD cases.     

Alcohol drinking frequency is more directly associated with alcohol use disorder than alcohol metabolizing enzymes among male Japanese

The development of alcohol use disorder (AUD) is related to various social, economic, cultural, environmental and hereditary factors. Several potential risk factors have been proposed for AUD in addition to alcohol consumption, including alcohol dehydrogenase2 (ADH2), acetaldehyde dehydrogenase2 (ALDH2), marital status, educational, occupational or past medical history (e.g. diabetes mellitus, hypertension, lung, digestive tract, or chronic liver disease) or smoking habits. The present study was performed to investigate the relationship between the aforementioned potential risk factors and AUD in Japan. A case-control study was performed on 153 male Japanese AUD patients and age-, gender-, or other confounder-matched controls to investigate the relation multivariately between ADH2, ALDH2 or alcohol drinking and AUD. Genomic DNA were extracted from nail clippings by the guanidium method, and genotyping of ADH2 and ALDH2 were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Univariate analyses by the conditional logistic regression model revealed statistically significant odds ratios due to ADH2*1/1 genotype, ALDH2*1/1 genotype, middle school as the final school attended, longest occupations as farmers, fishermen, craftsmen, miners, production process or construction workers, and past histories of chronic liver disease and AUD. However, multivariate analyses under a hierarchically well-formulated model strategy with interaction and confounding assessment indicated that (i) heavy alcohol intake was a significant risk factor (odds ratio per 1.0 g of daily ethanol intake; 1.096, 95% confidence interval; 1.026-1.171) for developing AUD after adjusting for other confounders; and (ii) ADH2*1/1 genotype and ALDH2*1/1 genotype were not risk factors after adjusting for daily ethanol intake and other confounders. The present study shows that AUD was more directly and strongly associated with alcohol drinking than with alcohol metabolizing enzymes among male Japanese.     

临床药师对抗菌药物使用强度指标调控的干预研究

目的：探讨和研究临床药师在抗菌药物使用强度指标控制中的作用。方法临床药师通过基础数据调查,参与制定医院抗菌药物使用强度（AUD）指标、定期监测和分析并针对各临床科室提出个性化的整改建议,加强抗菌药物处方点评、组织抗菌药物合理应用培训等方法,开展药学服务。结果我院抗菌药物使用强度指标大为下降,2013年下半年开始AUD值基本控制在40DDDs以下。结论临床药师可以从药学角度出发,充分发挥自身优势,提供合理化建议,有效降低医院AUD值。     

Pharmacotherapeutic management of co-morbid alcohol and opioid use

ABSTRACT

Opioid use disorder (OUD) and alcohol use disorder (AUD) are two highly prevalent substance-related disorders worldwide. Co-use of the substances is also quite prevalent, yet there are no pharmacological treatment approaches specifically designed to treat co-morbid OUD and AUD. Here, the authors critically summarize OUD, AUD and opioid/alcohol co-use and their current pharmacotherapies for treatment. They also review the mechanisms of action of opioids and alcohol within the brain reward circuitry and discuss potential combined mechanisms of action and resulting neuroadaptations. Pharmacotherapies that aim to treat AUD or OUD that may be beneficial in the treatment of co-use are also highlighted. Preclinical models assessing alcohol and opioid co-use remain sparse. Lasting neuroadaptations in brain reward circuits caused by co-use of alcohol and opioids remains largely understudied. In order to fully understand the neurobiological underpinnings of alcohol and opioid co-use and develop efficacious pharmacotherapies, the preclinical field must expand its current experimental paradigms of ‘single drug’ use to encompass polysubstance use. Such studies will provide insights on the neural alterations induced by opioid and alcohol co-use, and may help develop novel pharmacotherapies for individuals with co-occurring alcohol and opioid use disorders.     

Should symptom frequency be factored into scalar measures of alcohol use disorder severity?

Aims To evaluate whether weighting counts of alcohol use disorder (AUD) criteria or symptoms by their frequency of occurrence improves their association with correlates of AUD. Design and participants Data were collected in personal interviews with a representative sample of US adults interviewed in 1991–92. Analyses were conducted among past‐year drinkers (12+ drinks, n = 18 352) and individuals with past‐year DSM‐IV AUD (n = 2770). Measurements Thirty‐one symptom item indicators, whose frequency of occurrence was measured in eight categories, were used to create unweighted and frequency‐weighted counts of DSM‐IV past‐year AUD symptoms and criteria. Correlates included density of familial alcoholism and past‐year volume of ethanol intake, frequency of intoxication and utilization of alcohol treatment. Findings Although the AUD correlates were associated strongly and positively with the frequency of AUD symptom occurrence, weighting for symptom frequency did not strengthen their association consistently with AUD severity scores. Improved performance of the weighted scores was observed primarily among AUD correlates linked closely with the frequency of heavy drinking and among individuals with AUD. Criterion counts were correlated nearly as strongly as symptom counts with the AUD correlates. Conclusions Frequency weighting may add somewhat to the validity of AUD severity measures, especially those that are intended for use among individuals with AUD, e.g. in clinical settings. For studying the etiology and course of AUD in the general population, an equally effective and less time‐consuming alternative to obtaining symptom frequency may be the use of unweighted criterion counts accompanied by independent measures of frequency of heavy drinking.     

Alcohol addiction - the safety of available approved treatment options

Introduction: Alcohol Use Disorders (AUD) is a leading cause of mortality and morbidity worldwide. At present disulfiram, naltrexone and acamprosate are approved for the treatment of AUD in U.S. and Europe. Nalmefene is approved in Europe and sodium oxybate is approved in Italy and Austria only. Baclofen received a ‘temporary recommendation for use’ in France.

Areas covered: The safety of the above mentioned medications on liver, digestive system, kidney function, nervous system, pregnancy and lactation and their possible side effects are described and discussed.

Expert opinion: Mechanism of action and metabolism of these drugs as well as patients’ clinical characteristics can affect the safety of treatment. All approved medications are valid tools for the treatment of AUD in patients without advanced liver disease. For some drugs, attention should be paid to patients with renal failure and medications may be used with caution, adjusting the dosage according to kidney function. In patients with AUD and advanced liver disease, at present only baclofen has been formally tested in randomized controlled trials showing its safety in this population.     

Eliciting youth and adult recommendations through citizens’ juries to improve school based adolescent immunisation programs

Objectives

Completion of adolescent immunisation schedules in Australia is sub-optimal despite a well-established school based delivery program. The aim of this study was to seek adolescent and adult views on how existing adolescent school based immunisation policy and program delivery could be improved to increase adolescent immunisation uptake.

Method

Two citizens’ juries held separately, one with adolescent participants and one with adult participants deliberated on recommendations for public policy. Jury members were selected using a stratified sampling technique and recruited from a standing panel of community research participants through a market research company in South Australia. Juries were conducted in Metropolitan South Australia over two days and used university facilities with all meals and refreshments provided.

Results

Fifteen adults and 16 adolescents participated in the adult and youth juries respectively. Similar recommendations were made by both juries including increased ensuring the accuracy of information provided to adolescents and parents; employing a variety of formats for information delivery; and greater consideration of students’ physical and emotional comfort in order to improve the experience for adolescents. While the youth jury recommended that it should be compulsory for adolescents to receive vaccines through the school based immunisation program, the adult jury recommended an ‘opt-out’ system of consent. Both juries also recommended the use of incentives to improve immunisation uptake and immunisation course completion.

Conclusions

Eliciting adolescent views and including the perspectives of adolescents in discussions and development of strategies to improve engagement in the school based immunisation program provided valuable insight from the group most impacted by these policies and practices. Specifically, incorporation of adolescent and community views using citizens’ juries may lead to greater overall support from the community as their values and needs are more accurately reflected.