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.

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.

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).

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).

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).

Considerations over a Case of Suspected Therapeutic Failure in Pediatric Patients after Switching Valproate Manufacturers.

Introduction: Product switching followed by suspected adverse events are common and unsettling for antiepileptic drugs. The objective of this case study was to describe the investigation performed after report of suspected therapeutic failure in pediatric patients following a switch to a different valproate manufacturer and identify strategies concerning medication management for improving therapeutic outcomes. Case description: It was reported that different pediatric patients' condition changed (agitation/ seizures) after refilling the same drug prescription (sodium valproate syrup) from a different manufacturer. Medical staff reported a suspected therapeutic failure and some units of the product batch associated with the problem were seized by the local Post-marketing Surveillance Service for investigation of potential quality deviations. The seized units were evaluated by the State's Surveillance Laboratory, nevertheless, drug potency was found to be 98.7%. Conclusion: We consider that the reported event could be associated with aspects of medication use, i.e. potential dose measurement deviations resulting from remaining of residual liquid in the cup or eventual delay at prescription refilling process and consequential - even though brief - pharmacotherapy discontinuity. Patient education and counseling by pharmacists are essential for preventing drug-related problems and enhancing positive outcomes of pharmacotherapy.

Tobacco smoking and risk for dementia: evidence from the 10/66 population-based longitudinal study.

Objective: This study aimed to estimate the association between tobacco smoking and risk for dementia in seven low- and middle-income countries.Methods: Secondary analysis of the 10/66 population-based cohort study was conducted with 11,143 dementia-free individuals aged 65 years and older who were followed-up for an average of 3.8 years totalling 42,715 person-years. Cox regression with competing-risk analyses was used, controlling for age, gender, number of assets, past hazardous drinking, exercise and self-report of heart disease. Exposure was measured in packyears and smoking status. The number of packyears was calculated by multiplying the average number of packs per day by years of consumption up to 50 years old and up to age at baseline.Results: Meta-analysis of the results from each country yielded non-significant pooled relative risk ratios for all comparisons. There was no difference in risk for any dementia between 'ever smokers' compared to 'never smokers' (HR 0.96; 95% CI 0.82-1.13); 'current smokers' compared to 'never smokers' (HR 0.83; 95% CI 0.66-1.06); 'former smokers' compared to 'never smokers' (HR 1.06; 95% CI 0.88-1.27); 'current smokers' compared to 'former smokers' (HR 0.86; 95% CI 0.66-1.13). Results were similar for Alzheimer's disease (AD) and Vascular Dementia (VaD) as outcomes. Lifetime tobacco consumption (packyears) was not associated with any dementia (HR 1.00; 95% CI 0.99-1.00), nor with AD or VaD.Conclusion: Pooled results from all the countries showed no significant association between smoking and the onset of any dementia. Selective quitting in later-life might have biased the results towards no effect.

Unmet Quality Needs in Oral Drug Delivery: Contrasts of Drug Content and Uniformity on Distinct Approaches for Achieving Individual Dosing.

Individualized dosing is often required in pharmacotherapy, particularly for pediatric and geriatric patients and adjustment of drugs that demand dose adaptation. This study aimed to evaluate critical quality attributes (CQAs) of doses obtained by distinct approaches for achieving individual dosing. Approaches were evaluated as follows: subdivision of tablets by splitter and hand (haloperidol) and delivery by plastic dropper bottle (haloperidol), glass dropper bottle (clonazepam), dosing cup (sodium valproate), and dosing syringe (carbamazepine), including brand name, generic, and similar marketed products. Measuring devices were packaged with their respective product. Drug content uniformity was assessed to each substance according to pharmacopeial methods. Tablets subdivided by splitter had the poorest performance among all approaches, in which doses ranged around 60% of the labeled amount (Acceptance Value = 58.1 and RSD = 23.2%). The greatest performances were observed for the dosing syringe which fulfilled all the requirements for dose precision and for the glass dropper bottle. There were significant differences in dose delivery between manufacturers of the same medicine when measuring the same volume or number of drops. High drug content variability is extremely harmful to pharmacotherapy and may result in therapeutic failure or toxicity. It is crucial that measuring devices and scoring of tablets be checked for functionality and standardized for different manufacturers of the same medicine. Part of the approaches for achieving individual dosing did not meet the quality needs for drug content and uniformity. Yet, our findings show that more accurate and precise dosing can be accessed when using the dosing syringe and glass dropper bottle.

Mania-like elevated mood in rats: Enhanced 50-kHz ultrasonic vocalizations after sleep deprivation.

Mania is characterized by elevated drive and mood but animal models of mania have often neglected elevated mood. Ultrasonic vocalizations (USV) of 50-kHz emitted by rats are thought to index the subject's positive affective state. Fifty-kHz USV emission is increased by amphetamine, an effect blocked by lithium administration. Sleep deprivation (SD) is an environmental model of mania and the present study evaluated SD effects on behavioral activity and USV emission, together with the impact of lithium treatment. Adult rats were submitted to 24h or 72h SD, and locomotor activity and USV emission were assessed. To test their sensitivity to a standard antimanic drug, these behavioral parameters were also evaluated after acute administration of lithium carbonate (25, 50 or 100 mg/kg, i.p.). Striatal monoamine content was measured post-mortem. SD (24h and 72h) led to increased locomotor activity, rearing behavior and 50-kHz USV emission, together with a change in the call profile characterized by an increase in the percentage of frequency-modulated 50-kHz USV, which may indicate the mania-like consequences of SD. Importantly, all SD effects were reverted by lithium administration. SD also led to a decrease in dopamine content in the ventral striatum, while increasing dopamine turnover. In conclusion, SD increased 50-kHz USV emission, an effect prevented by acute lithium administration. This suggests 50-kHz USV as a new marker for mania-like elevated mood, which shows construct validity (associated with increased dopaminergic tone), face validity (reflecting increased positive affect) and predictive validity (high sensitivity to lithium treatment).