Preliminary investigation of the administration of biperiden to reduce relapses in individuals with cocaine/crack user disorder: A randomized controlled clinical trial.

BACKGROUND: Several studies have demonstrated that ACh modulates the dopaminergic circuit in the nucleus accumbens, and its blockade appears to be associated with the inhibition of the reinforced effect or the increase in dopamine caused by cocaine use. The objective of this study was to evaluate the effect of biperiden (a muscarinic receptor antagonist with a relatively higher affinity for the M1 receptor) on crack/cocaine use relapse compared to a control group that received placebo. METHODS: This study is a double-blind, randomized, placebo-controlled clinical trial. The intervention group received 2 mg of biperiden, 3 times a day, for a period of 3 months. The control group received identical placebo capsules, at the same frequency and over the same period. All participants were followed for a period of six months. RESULTS: The sample comprised 128 people, with 61 in the control group and 67 in the biperiden group. Lower substance consumption was observed in the group that received biperiden treatment two (bT2 = -2.2 [-3.3; -1.0], p < 0.001) and six months (bT4 = -6, 2 [-8.6; -3.9], p < 0.001) after the beginning of the intervention. The biperiden group had a higher latency until a possible first day of consumption, in the same evaluation periods (bT2 = 0.26 [0.080; 0.44], p = 0.004; bT4 = 0.63 [0.32; 0.93], p < 0.001). CONCLUSIONS: Despite the major limitations of the present study, the group that received biperiden reduced the number of days of cocaine/crack use and showed an increase in the latency time for relapse. More studies are needed to confirm the utility of this approach.

Neuroscience-Based Nomenclature (NbN): the Portuguese version of the new classification for psychopharmacological drugs.

Neuroscience-Based Nomenclature (NbN) is a proposal to provide a nomenclature based on neuroscience and pharmacology instead of the old disease-based classification. NbN is based on the mechanism of action and pharmacological target and aims to assist in rational prescription, reduce stigma, and increase treatment adherence. Currently, NbN is endorsed by many psychiatric associations, adopted by several relevant journals, and included in major psychiatry textbooks. Therefore, it is important that NbN is known to psychiatrists.

Current strategies for tapering psychiatric drugs: Differing recommendations, impractical doses, and other barriers.

While effective ways to prevent withdrawal symptoms from psychiatric drugs remain unclear, a highly accepted clinical approach for treatment discontinuation is to gradually reduce doses over time. The objective of this review is to gather the current strategies for tapering of psychiatric drugs described in the literature and guidelines in an attempt to identify the most promising one. Literature review and search for practice guidelines provided by government agencies and medical organizations were performed. Different strategies for tapering were found: linear tapering, hyperbolic tapering (by exponential dose reduction and pre-established dose-response curves), extended dosing, and substitution for a long half-life drug. The use of guidelines offers support for patients and prescribers, increasing the likelihood of achieving effective drug discontinuation. Nevertheless, the lack of standardization found among the guidelines makes any attempt to reduce or stop the drug very difficult for prescribers. Hyperbolic tapering by exponential dose reduction appears to be the most promising strategy for psychiatric drug discontinuation. Yet, we still face a constant challenge: how to safely obtain flexible doses for the discontinuation of drugs, particularly during the last steps in which lower doses are required. Further studies are needed to reduce the barriers associated with psychiatric drug discontinuation.

A Systematic Review on Alcohol Consumption among Non-Religious and Religious Adults.

Background: Research has suggested that religiosity is a protective factor in alcohol use, but this is an area that could be further explored. Objective: To undertake a systematic review of the literature on drinking patterns and their relationship with religiosity and non-religiosity in adult populations. Methods: We searched for relevant studies using the PubMed, LILACS, Web of Science, Scopus, and Psych-INFO databases. This review included only studies of people aged 18 and over which had a non-religious group as a comparison measure. Results: Fifty-one studies met the inclusion criteria. The present review showed that religious people tend to have lower alcohol consumption compared to those with no religion. However, this difference appears only when religions are analyzed together without differentiating between religious affiliations (Catholicism, Buddhism, Evangelicalism, etc.). Some religious affiliations, such as Buddhism, Catholicism and Lutheranism, appear to be risk factors for alcohol consumption. Definitions of risk consumption showed high heterogeneity, ranging from eight to 21 or more doses per week, a difference of 13 doses of alcohol between studies. Conclusions: The present review showed that religious people tend to have lower alcohol consumption compared to non-religious people. However, the results are contradictory when religious affiliations are analyzed separately and compared with non-religious participants. Adequately understanding which dimensions of religiosity and non-religiosity (e.g., group processes, engagement, meaning, rules of behavior) are protective in adulthood is fundamental to the construction of more effective interventions in this age group.

Religious and secular spirituality: Methodological implications of definitions for health research.

The importance of spirituality as a research topic has been increasingly recognized, which has led to several studies on the topic. Areas including psychology, medicine, and nursing have produced studies on spirituality under a plurality of definitions and methods, which reveals the complexity of the theme. However, this has resulted in a range of potential problems, including: (1) the use of overlapping and contradictory terms between studies, or even within the same study, (2) research methodologies that do not fit the definitions (sometimes unreflectively) assumed by the authors, (3) difficulties, or even the impossibility, of comparing the results of studies, (4) controversies in respect of the inclusion/exclusion of secular groups in research on spirituality, and (5) ambiguous measurements, often being exclusively dependent on each participant's individual interpretation of what spirituality means. This article discusses these problems, recommends theoretical and methodological alternatives and presents taxonomy of definitions of spirituality.

Omega-3 for the Prevention of Alcohol Use Disorder Relapse: A Placebo-Controlled, Randomized Clinical Trial.

Background: Recent studies have sought to identify the possible benefits of the intake of omega-3, an important component of neuronal membranes, for the treatment of alcohol use disorder. Aim: The objective of the present study was to evaluate whether omega-3 supplementation is protective against alcohol use disorder relapse after hospital discharge. Methods: A randomized, double-blind, placebo-controlled study was carried out with severe alcohol dependence. Male inpatients were randomized to treatment with omega-3 (n = 59) or placebo (n = 52) for 3 months, participants were assessed after discharge at 1 month (T1), 2 months (T2), 3 months (T3), and 6 months (T4) with assessments made using self-report instruments. The primary outcomes were the possible reduction with assessments made using self-report instruments. The primary outcomes were the possible reduction in the number, intensity of relapses, amount of consumption in each relapse and number of days of consumption during relapses; as secondary outcomes were assessed symptoms of anxiety, depression, degree of dependence, compulsion, and craving. Results: The groups were similar regarding consumption amount parameters and propensity to relapse; however, an effect of treatment with omega-3 was found on the number of days of drinking at 2 months [B = 0.65 (0.09; 1, 21), p = 0.01] and 3 months [B = 2.6 (1.61; 3.58), p < 0.001] after discharge, favoring the intervention group. The effect was not maintained at follow up of 6 months. No differences were found in psychiatric symptoms and severity of addiction. Conclusion: Despite the major limitations of the present study, the group that received omega-3 had a lower number of days of consumption of standard doses of alcohol in the evaluations of 60 and 90 days after discharge. More robust studies are needed to confirm or refute these findings. Brazilian Registry of Clinical Trials: n° RBR-48mkgz7 (URL: https://ensaiosclinicos.gov.br/rg/RBR-48mkgz7).

Drug Use Frequency Variation and Mental Health During the COVID-19 Pandemic: an Online Survey.

In December 2019, a new disease caused by a coronavirus was first identified in China and quickly spread across the world, causing a large number of deaths. Quarantine has been implemented in many countries as a measure to prevent the spread of the disease. The impact of this situation on drug use and mental health is still poorly understood. Therefore, this cross-sectional study sought to assess possible associations between quarantine, the use of psychoactive substances, and symptoms of depression and anxiety. The assessment instruments used were the Patient Health Questionnaire-9 (PHQ-9); the General Anxiety Disorder-7 (GAD-7) scale; and an adaptation of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The sample consisted of 2398 participants who met the following inclusion criteria: being in quarantine, aged 18 years or older, and living in Brazil. There was a decrease in the frequency of use of practically all drugs investigated in the evaluated sample. However, some factors were associated with less variations in the frequency of substance use before and during quarantine. These factors were being male, single, and having an occupation different from homemaker.

The effect of sleep medications on prospective and retrospective memory: a population-based study.

Sleep medications, especially benzodiazepines, are known to cause motor and cognitive impairments as side-effects from their use. However, an evaluation of the effects of sleep medications in general on prospective and retrospective memory remains to be seen. Thus, the effects of the different types of sleep medicines were assessed using the total score and the 8 subscales of the Prospective and Retrospective Memory Questionnaire (PRMQ) in a representative sample from the Municipality of São Paulo. The effects of each type of medication on these same parameters were evaluated afterwards. Each analysis was performed controlling for different covariates to observe their degree of interference on the observed results. Impairment due to use of sleep aid medication was observed in 6 of the 8 subscales, as well in the overall score of the PRMQ when compared to non-users. Prospective subscales were particularly affected, even when controlling for highly interfering covariates such as depression and anxiety, and objective sleep variables related to sleep architecture and wakefulness in the night. Few effects were detected between the various types of medication even when controlling for covariates, suggesting that a sample with higher power is necessary to conduct a more detailed analysis. Using pharmacological aids to improve sleep may impair prospective and (to some extent) retrospective memory. Therefore, the relationship between sleep impairment, memory deficits and medication use must be considered by physicians.

Effects of Risperidone in Autistic Children and Young Adults: A Systematic Review and Meta-Analysis.

There are several studies investigating the effects of risperidone on autism, but many of these studies are contradictory or inconclusive. This systematic review and meta-analysis investigated the effects of risperidone on five domains of the Aberrant Behaviour Checklist (ABC) scale on Autism Spectrum Disorder (ASD), as well as weight gain and waist circumference. The protocol for the present systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO). For this study, we analysed articles (2,459), selecting them according to the PICOS strategy (Population, Intervention, Comparison, Outcome, Study design). Although risperidone is effective for the treatment of lethargy and inadequate speech, concerns about the association between weight gain, waist circumference and risperidone require a need for evaluation of the risk-benefit ratio in its use. There was a significant association between weight gain, waist circumference and risperidone. In conclusion, it was possible to suggest the efficacy of risperidone for the treatment of lethargy and inadequate speech. Finally, we emphasize that the risk-benefit in its use should be evaluated (Protocol number CRD42019122316).

Association between polymorphism in gene related to the dopamine circuit and motivations for drinking in patients with alcohol use disorder.

The development of alcohol use disorder (AUD) is influenced by genetic, psychological, and social factors. However, the identification of the load of each of these factors and the association between them is still debatable. This study aimed to explore the load of the association between AUD and polymorphisms in genes of the dopaminergic system, as well as with drinking triggers. The study comprised 227 inpatients with AUD and 174 controls. The pattern and motivations for drinking were evaluated using the Alcohol Use Disorders Identification Test (AUDIT) and the Inventory of Drinking Situations (IDS). Analyses of genetic variation in genes encoding dopaminergic were performed using next generation sequencing. We observed an significant association between a polymorphism in DDC (rs11575457) and AUD. Positive reinforcement factors as urges/temptations to drink and pleasant emotion, in isolation, were the significantly related elements to drinking. In addition, negative (physical discomfort) and positive reinforcement factors (testing personal control; pleasant time with others) significantly reinforced the interaction with DDC genetic variant for increased odds of an individual presenting AUD. These results indicated a complex relationship between the dopaminergic system and the drug-seeking behavior profiles.

Combined cocaine and clonazepam administration induces REM sleep loss and anxiety-like withdrawal behaviors in rats.

Misuse of prescription medications has risen to popularity. Reasons for this practice include the self-medication of sleep and psychiatric disorders and attempts to counteract the dysphoric side effects of stimulant drugs. Clonazepam, a commonly prescribed benzodiazepine, has been increasingly used as a countermeasure to cocaine side-effects, including sleep reduction and anxiety. As both substances may impair sleep and aggravate psychiatric conditions, this study aimed to evaluate the long-term effects of the interaction of clonazepam and cocaine on anxiety-like behavior, and the short-term effects of this drug combination on sleep using male Wistar rats. Animals received saline, cocaine (15 mg/kg), clonazepam (1.25 mg/kg) or both drugs for 16 days. Sleep recording was performed on the first day of treatment to evaluate acute treatment effects. One day after the end of the treatment period, the open field and elevated plus-maze tests were used to assess anxiety-like behavior. Blood samples were collected for analysis of corticosterone levels. Rats receiving both drugs presented an increase in impulsivity when moving between arms in the elevated plus-maze and a reduction in exploratory behavior in the open field test. These findings suggest the presence of a withdrawal behavioral syndrome, which can manifest as a paradoxical increase in exploratory activity after a period without receiving the drug and may indicate the development of dependence. Combined treatment reduced paradoxical sleep time and increased its onset latency. There was no significant difference regarding corticosterone levels across any group. Our results contribute to the understanding of the risks of combining cocaine and clonazepam. Association of these drugs may impair sleep architecture and aggravate the dependence symptoms already seen when these substances are used separately. These findings may be useful in helping to counteract the impairments resulting from the combined use of these 2 substances and to raise awareness of these associated risks.

Risk factors associated with drug therapy among elderly people with Alzheimer's disease: a cross-sectional study.

BACKGROUND: Improving knowledge and establishing strategies and policies for better patient safety are worldwide priorities. OBJECTIVE: To evaluate drug safety among elderly people with Alzheimer's disease (AD). DESIGN AND SETTING: Cross-sectional study among elderly people within the National AD Assistance Protocol (PCDTDA/MS) who were living in the municipality of Araraquara, Brazil, in 2017. METHODS: Through interviews conducted with relatives/caregivers of elderly people with diagnoses of AD, the following variables were evaluated: comorbidities, drug therapy used, use of potentially inappropriate medications for the elderly (PIMs), presence of potentially inappropriate interactions (PIIs) and medication regimen complexity index. Factors associated with AD severity were also evaluated. Multivariate and simple logistic regressions were applied. RESULTS: 143 elderly people enrolled in PCDTDA/MS were analyzed. The majority were women (67.1%); assisted only through the public healthcare system (75.5%); polymedicated (57.4%); using at least one PIM (63.6%); presenting at least one PII (63.6%); and under drug therapy of low to medium complexity (92.2%). No semi-annual monitoring of the effectiveness of PCDTDA/MS drugs was identified. The proportion using AD drug therapy at daily doses differing from those recommended by the World Health Organization was 75.6%. However, these doses were not associated with drug risk. CONCLUSION: The data from this study raise the hypothesis that use of polypharmacy might show a correlation with severity of AD. The drug safety risk may be associated with comorbidities of the metabolic syndrome, anxiety and off-label use of PIMs, such as risperidone and quetiapine, and benzodiazepines (i.e. clonazepam and flunitrazepam).

Risk factors associated with drug therapy among elderly people with Alzheimers disease: a cross-sectional study

ABSTRACT BACKGROUND: Improving knowledge and establishing strategies and policies for better patient safety are worldwide priorities. OBJECTIVE: To evaluate drug safety among elderly people with Alzheimer's disease (AD). DESIGN AND SETTING: Cross-sectional study among elderly people within the National AD Assistance Protocol (PCDTDA/MS) who were living in the municipality of Araraquara, Brazil, in 2017. METHODS: Through interviews conducted with relatives/caregivers of elderly people with diagnoses of AD, the following variables were evaluated: comorbidities, drug therapy used, use of potentially inappropriate medications for the elderly (PIMs), presence of potentially inappropriate interactions (PIIs) and medication regimen complexity index. Factors associated with AD severity were also evaluated. Multivariate and simple logistic regressions were applied. RESULTS: 143 elderly people enrolled in PCDTDA/MS were analyzed. The majority were women (67.1%); assisted only through the public healthcare system (75.5%); polymedicated (57.4%); using at least one PIM (63.6%); presenting at least one PII (63.6%); and under drug therapy of low to medium complexity (92.2%). No semi-annual monitoring of the effectiveness of PCDTDA/MS drugs was identified. The proportion using AD drug therapy at daily doses differing from those recommended by the World Health Organization was 75.6%. However, these doses were not associated with drug risk. CONCLUSION: The data from this study raise the hypothesis that use of polypharmacy might show a correlation with severity of AD. The drug safety risk may be associated with comorbidities of the metabolic syndrome, anxiety and off-label use of PIMs, such as risperidone and quetiapine, and benzodiazepines (i.e. clonazepam and flunitrazepam).