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The use of controlled substances (narcotics and psychotropic substances) poses increased risks for minors. However, minors are generally excluded from existing harm reduction services (e.g. drug consumption rooms, drug checking, exchange of consumption material). Based on public health considerations, the authors recommend the establishment of harm reduction services for minors.

Rationale Use of psychotropics is relatively prevalent amongst motor vehicle drivers because mobility is also important for persons suffering from psychiatric illness. However, medication side effects may increase the likelihood of being involved in traffic crashes. Objectives This study aimed to assess the association between the use of four types of medication (antipsychotics, benzodiazepines and z-hypnotics, antidepressants and stimulants of ADHD treatment) and the risk of traffic crashes, in general, and single crashes subsequently. Method We conducted a case–control study of data from 130,000 drivers involved in traffic crashes with personal injury and prescription data from all of Denmark during the period 1996–2018. Results For antipsychotics, we found odds ratios of 0.86 and 1.29 for traffic crashes and single crashes, respectively; for benzodiazepines and z-hypnotics, 1.29 and 2.49, respectively; for antidepressants, 1.30 and 2.25, respectively; and for stimulants of ADHD treatment, 1.62 and 1.95, respectively. All p values were below 0.001. Conclusions Based on our results on twofold increased risks of single crashes and moderately increased risks in persons with ADHD, it might seem tempting to ban psychotropic medication in traffic. Conversely, we accept increased risks of traffic crashes in young drivers and in the physically disabled with special aids and, to some extent, with exposure to alcohol. In the end, it is the authorities who must review the evidence and decide whether to prohibit (some types of) psychotropic medication in traffic. Finally, underlying disease and not the drug may increase the risk of being involved in a traffic crash.

Background Several psychotropic drugs can induce weight gain and metabolic alterations. The authors compared metabolic evolutions of patients switching versus continuing psychotropic treatments with different risk profiles. Methods Patients either switched from a high- to a medium- (N = 36) or low-risk drug (N = 27), from a medium- to a low-risk drug (N = 71), or to a same-risk drug (N = 61). Controls were kept using either a high- (N = 35), medium- (N = 155), or low-risk drug (N = 47). The evolution over 2 years of weight and metabolic parameters was analyzed using linear mixed-effect models, also examining the influence of polygenic risk scores for body mass index (BMI) or BMI and psychiatric disorders. Study Results High-, medium-, or low-risk controls gained on average 1.32%, 0.42%, and 0.36% more weight per month than patients switching from or within these risk categories (P Conclusion Psychotropic switches to a lower- or same-risk drug can attenuate weight gain, with only switching high to low resulting in weight loss.

Rationale: Use of psychotropics is relatively prevalent amongst motor vehicle drivers because mobility is also important for persons suffering from psychiatric illness. However, medication side effects may increase the likelihood of being involved in traffic crashes. Objectives: This study aimed to assess the association between the use of four types of medication (antipsychotics, benzodiazepines and z-hypnotics, antidepressants and stimulants of ADHD treatment) and the risk of traffic crashes, in general, and single crashes subsequently. Method: We conducted a case–control study of data from 130,000 drivers involved in traffic crashes with personal injury and prescription data from all of Denmark during the period 1996–2018. Results: For antipsychotics, we found odds ratios of 0.86 and 1.29 for traffic crashes and single crashes, respectively; for benzodiazepines and z-hypnotics, 1.29 and 2.49, respectively; for antidepressants, 1.30 and 2.25, respectively; and for stimulants of ADHD treatment, 1.62 and 1.95, respectively. All p values were below 0.001. Conclusions: Based on our results on twofold increased risks of single crashes and moderately increased risks in persons with ADHD, it might seem tempting to ban psychotropic medication in traffic. Conversely, we accept increased risks of traffic crashes in young drivers and in the physically disabled with special aids and, to some extent, with exposure to alcohol. In the end, it is the authorities who must review the evidence and decide whether to prohibit (some types of) psychotropic medication in traffic. Finally, underlying disease and not the drug may increase the risk of being involved in a traffic crash.

Psychological distress following cancer diagnosis may lead to mental health complications including depression and anxiety. Non-Hodgkin lymphomas (NHLs) include indolent and aggressive subtypes for which treatment and prognosis differ widely. Incident use of psychotropic drugs (PDs - antidepressants, antipsychotics, and anxiolytics) and its correlation to lymphoma types can give insights into the psychological distress these patients endure. In this prospective matched cohort study, we used nationwide population-based registries to investigate the cumulative risk of PD use in NHL patients compared to a sex- and age-matched cohort from the Danish background population. In addition, contact patterns to psychiatric departments and incident intentional self-harm or completed suicide were explored. In total, 8,750 NHL patients and 43,750 matched comparators were included (median age 68; male:female ratio 1.6). Median follow-up was 7.1 years. Two-year cumulative risk of PD use was higher in NHL patients (16.4%) as compared to the matched comparators (5.1%, p

Insomnia disorders as well as cardiometabolic disorders are highly prevalent in the psychiatric population compared to the general population. We aimed to investigate their association and evolution over time in a Swiss psychiatric cohort. Data for 2861 patients (8954 observations) were obtained from two prospective cohorts (PsyMetab and PsyClin) with metabolic parameters monitored routinely during psychotropic treatment. Insomnia disorders were based on the presence of ICD-10 "F51.0" diagnosis (non-organic insomnia), the prescription of sedatives before bedtime or the discharge letter. Metabolic syndrome was defined using the International Diabetes Federation definition, while the 10-year risk of cardiovascular event or death was assessed using the Framingham Risk Score and the Systematic Coronary Risk Estimation, respectively. Insomnia disorders were observed in 30% of the cohort, who were older, predominantly female, used more psychotropic drugs carrying risk of high weight gain (olanzapine, clozapine, valproate) and were more prone to suffer from schizoaffective or bipolar disorders. Multivariate analyses showed that patients with high body mass index (OR = 2.02, 95%CI [1.51-2.72] for each ten-kg/m 2 increase), central obesity (OR = 2.20, [1.63-2.96]), hypertension (OR = 1.86, [1.23-2.81]), hyperglycemia (OR = 3.70, [2.16-6.33]), high density lipoprotein hypocholesterolemia in women (OR = 1.51, [1.17-1.95]), metabolic syndrome (OR = 1.84, [1.16-2.92]) and higher 10-year risk of death from cardiovascular diseases (OR = 1.34, [1.17-1.53]) were more likely to have insomnia disorders. Time and insomnia disorders were associated with a deterioration of cardiometabolic parameters. Insomnia disorders are significantly associated with metabolic worsening and risk of death from cardiovascular diseases in psychiatric patients.

Background The objective of this study was to investigate the relation of severe COVID-19 to prior drug prescribing. Methods Severe cases were defined by entry to critical care or fatal outcome. For this matched case-control study (REACT-SCOT), all 4251 cases of severe COVID-19 in Scotland since the start of the epidemic were matched for age, sex and primary care practice to 36,738 controls from the population register. Records were linked to hospital discharges since June 2015 and dispensed prescriptions issued in primary care during the last 240 days. Results Severe COVID-19 was strongly associated with the number of non-cardiovascular drug classes dispensed. This association was strongest in those not resident in a care home, in whom the rate ratio (95% CI) associated with dispensing of 12 or more drug classes versus none was 10.8 (8.8, 13.3), and in those without any of the conditions designated as conferring increased risk of COVID-19. Of 17 drug classes postulated at the start of the epidemic to be “medications compromising COVID”, all were associated with increased risk of severe COVID-19 and these associations were present in those without any of the designated risk conditions. The fraction of cases in the population attributable to exposure to these drug classes was 38%. The largest effect was for antipsychotic agents: rate ratio 4.18 (3.42, 5.11). Other drug classes with large effects included proton pump inhibitors (rate ratio 2.20 (1.72, 2.83) for = 2 defined daily doses/day), opioids (3.66 (2.68, 5.01) for = 50 mg morphine equivalent/day) and gabapentinoids. These associations persisted after adjusting for covariates and were stronger with recent than with non-recent exposure. Conclusions Severe COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression, or dyskinesia; have anticholinergic effects; or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. Measures to reduce the burden of mortality and morbidity from COVID-19 should include reinforcing existing guidance on reducing overprescribing of these drug classes and limiting inappropriate polypharmacy. Registration ENCEPP number https://EUPAS35558

Psychiatric patients are known to be at high risk of developing cardiovascular diseases (CVDs), leading to an increased mortality rate. To assess the CVD risk (presence of metabolic syndrome [MetS] and calculated 10-year CVD risk) in a Swiss psychiatric cohort taking weight gain-inducing psychotropic drugs, compare the findings to a Swiss population-based cohort, and evaluate the prevalence of participants treated for metabolic disruptions in both cohorts. Data for 1,216 psychiatric patients (of whom 634 were aged 35-75 years) were obtained between 2007 and 2017 from a study with metabolic parameters monitored during psychotropic treatment and between 2003 and 2006 for 6,733 participants from the population-based CoLaus|PsyCoLaus study. MetS as defined by the International Diabetes Federation (IDF) was identified in 33% of the psychiatric participants and 24.7% of the population-based subjects. Specifically, prevalence per the IDF definition was more than 3 times higher in the psychiatric cohort among women aged 35 to 49 years (25.6% vs 8.0%; P < 10-4). The psychiatric and population-based cohorts, respectively, had comparable predicted CVD risk (10-year risk of CVD event > 20%: 0% vs 0.1% in women and 0.3% vs 1.8% [P = .01] in men; 10-year risk of CVD death > 5%: 8.5% vs 8.4% [P = .58] in women and 13.4% vs 16.6% [P = .42] in men). No difference was observed among the proportion of participants with MetS treated for metabolic disturbances in the two cohorts, with the exception of women aged 35-49 years, for whom those in the psychiatric cohort were half as likely to receive treatment compared to participants in CoLaus|PsyCoLaus (17.8% vs 38.8% per the IDF definition; P = .0004). These findings emphasize the concern that psychiatric patients present an altered metabolic profile and that they do not receive adequate treatment for metabolic disruptions. Presence of metabolic disturbances should be routinely assessed, and adequate follow-up is needed to intervene early after illness onset.

Genetic factors associated with Body Mass Index (BMI) have been widely studied over the last decade. We examined whether genetic variants previously associated with BMI in the general population are associated with cardiometabolic parameter worsening in the psychiatric population receiving psychotropic drugs, a high-risk group for metabolic disturbances. Classification And Regression Trees (CARTs) were used as a tool capable of describing hierarchical associations, to pinpoint genetic variants best predicting worsening of cardiometabolic parameters (i.e total, HDL and LDL-cholesterol, triglycerides, body mass index, waist circumference, fasting glucose, and blood pressure) following prescription of psychotropic drugs inducing weight gain in a discovery sample of 357 Caucasian patients. Significant findings were tested for replication in a second Caucasian psychiatric sample (n=140). SH2B1 rs3888190C>A was significantly associated with LDL levels in the discovery and in the replication sample, with A-allele carriers having 0.2mmol/l (p=0.005) and 0.36mmol/l (p=0.007) higher LDL levels compared to others, respectively. G-allele carriers of RABEP1 rs1000940A>G had lower fasting glucose levels compared to others in both samples (-0.16mmol/l; p

Background Cardiovascular diseases and dyslipidemia represent a major health issue in psychiatry. Many psychotropic drugs can induce a rapid and substantial increase of blood lipid levels. Objective This study aimed to determine the potential predictive power of an early change of blood lipid levels during psychotropic treatment on long-term change and on dyslipidemia development. Methods Data were obtained from a prospective study including 181 psychiatric patients with metabolic parameters monitored during the first year of treatment and with adherence ascertained. Blood lipid levels (ie, total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non–high-density lipoprotein cholesterol [non-HDL-C], and fasting triglycerides [TGs]) were measured at baseline and after 1, 3, and/or 12 months of treatment. Results Receiver-operating characteristic analyses indicated that early (ie, after 1 month of psychotropic treatment) increases (≥5%) for TC, LDL-C, TG, and non-HDL-C and decrease (≥5%) for HDL-C were the best predictors for clinically relevant modifications of blood lipid levels after 3 months of treatment (≥30% TC, ≥40% LDL-C, ≥45% TG, ≥55% non-HDL-C increase, and ≥20% HDL-C decrease; sensitivity 70%–100%, specificity 53%–72%). Predictive powers of these models were confirmed by fitting longitudinal multivariate models in the same cohort ( P ≤ .03) as well as in a replication cohort (n = 79; P ≤ .003). Survival models showed significantly higher incidences of new onset dyslipidemia (TC, LDL-C, and non-HDL-C hypercholesterolemia, HDL-C hypocholesterolemia, and hypertriglyceridemia) for patients with early changes of blood lipid levels compared to others ( P ≤ .01). Conclusion Early modifications of blood lipid levels following prescription of psychotropic drugs inducing dyslipidemia should therefore raise questions on clinical strategies to control long-term dyslipidemia.

BACKGROUND: Psychotropic drugs can induce significant (>5%) weight gain (WG) already after 1 month of treatment, which is a good predictor for major WG at 3 and 12 months. The large interindividual variability of drug-induced WG can be explained in part by genetic and clinical factors. AIM: The aim of this study was to determine whether extensive analysis of genes, in addition to clinical factors, can improve prediction of patients at risk for more than 5% WG at 1 month of treatment. METHODS: Data were obtained from a 1-year naturalistic longitudinal study, with weight monitoring during weight-inducing psychotropic treatment. A total of 248 Caucasian psychiatric patients, with at least baseline and 1-month weight measures, and with compliance ascertained were included. Results were tested for replication in a second cohort including 32 patients. RESULTS: Age and baseline BMI were associated significantly with strong WG. The area under the curve (AUC) of the final model including genetic (18 genes) and clinical variables was significantly greater than that of the model including clinical variables only (AUCfinal: 0.92, AUCclinical: 0.75, P

SUMMARY: The effect of dopaminergic medication on the risk of hip/femur fractures is not clear. Our results showed a nearly twofold increased risk of hip/femur fractures in current dopaminergic drug users. Concomitant use of antidepressants further increased this risk. Fracture risk assessment may be warranted in elderly users of dopaminergic drugs.INTRODUCTION: Dopaminergic drugs, often used in the treatment of Parkinson's disease, have several pharmacological effects that may increase or decrease the risk of falling and fractures. Thus, the effect of dopaminergic medication on the risk of hip/femur fractures is not clear. The objective of the study was to examine the effect of dopaminergic medication and concomitant use of psychotropics on the risk of hip/femur fractures taking into account the timing of dopaminergic drug use.METHODS: A population-based case-control study in the PHARMO database was conducted for the period 1991 to 2002. Cases were patients aged 18 years and older with a first hip or femur fracture and matched to four control patients by year of birth, sex and geographical region.RESULTS: The study population included 6,763 cases and 26,341 controls. Current use of dopaminergic drugs (1-30 days before the index date) was associated with an increased risk of hip/femur fractures compared to never use (OR(adj) 1.76, 95% CI = 1.39-2.22), but this excess risk rapidly dropped to baseline levels when treatment had been discontinued >1 year ago. Concomitant use of antidepressants among current dopaminergic drug users further increased the risk of hip/femur fractures (OR(adj) 3.51, 95% CI = 2.10-5.87) while there was no additional risk with concomitant use of other psychotropics.CONCLUSIONS: Although the observed association between dopaminergic drugs and fracture risk may not be entirely causal, due to absence of information on the (severity of the) underlying disease, fracture risk assessment may be warranted in elderly users of dopaminergic drugs.

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n(1) = 168, n(2) = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m(2), n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m(2), n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r(2) = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

Copyright © 2014 Giovanni Martinotti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Date of Acceptance: 09/11/2014

To describe the weight gain-related side-effects of psychotropic drugs and their consequences on metabolic complications (hypercholesterolemia, obesity) in a Swiss cohort of psychiatric patients.This cross-sectional observational study was performed in an out-patient psychiatric division with patients having received for more than 3 months the following drugs: clozapine, olanzapine, quetiapine, risperidone, lithium, and/or valproate. Clinical measures and lifestyle information (smoking behaviour, physical activity) were recorded.196 inclusions were completed. Weight gain (≥10% of initial weight) following drug treatment was reported in 47% of these patients. Prevalence of obesity (BMI ≥ 30), hypercholesterolemia (≥6.2 mmol/L) and low HDL-cholesterol (1.0 mmol/L in men,1.3 mmol/L in women) were present in 38%, 21%, and 27% of patients, respectively. A higher standardised dose, an increase of appetite following medication introduction, the type of medication (clozapine or olanzapine quetiapine or risperidone lithium or valproate), and the gender were shown to be significantly associated with evolution of BMI.High prevalence of obesity and hypercholesterolemia was found in an out-patient psychiatric population and confirms drug-induced weight gain complications during long-term treatment. The results support the recently published recommendations of monitoring of metabolic side-effects during treatment with atypical antipsychotics. Moreover, the weight gain predictors found in the present study could help to highlight patients with special health care management requirement.

BACKGROUND: Adverse neuromuscular events have been described in case of low serum 25-hydroxyvitamin D (25OHD) concentrations, suggesting that vitamin D may be involved in gait stability. The objective of this cross-sectional study was to examine the association between stride-to-stride variability of stride time (STV) and serum 25OHD concentration in adults aged 65 years and older. METHODS: STV and 25OHD concentration were assessed in 411 community-dwelling older adults (mean age 70.4 +/- 1.8 years, 57.9% women). The following established 25OHD thresholds were used: severe 25OHD insufficiency 30 ng/mL. Age, number of drugs used per day, use of psychoactive drugs, depressive symptoms, cognitive decline, history of falls, distance visual acuity, lower limb proprioception, center of mass (CoM) motion, and walking speed were considered as potential confounders. RESULTS: A total of 16.6% (n = 68) of subjects had severe 25OHD insufficiency, 70.3% (n = 289) moderate insufficiency, and 13.1% (n = 54) normal concentrations. In the full adjusted and the stepwise backward linear regression models, high STV (worse performance) was associated with severe 25OHD insufficiency (p = 0.028 and p = 0.044, respectively), high CoM motion (p = 0.031 and p = 0.014, respectively), and low lower limb proprioception score (p = 0.017 and p = 0.008, respectively). The stepwise backward regression model also showed that high STV was associated with female gender (p = 0.041). CONCLUSIONS: Low serum 25OHD concentrations were associated with high STV reflecting a disturbed gait control. This association could be explained by a possible action of vitamin D on different components involved in gait control.

La Fondation Nez rouge a mandaté l'Institut universitaire de médecine sociale et préventive de Lausanne (IUMSP) pour une évaluation de leur action pendant la Fête des Vignerons 1999. Le but de cette étude était de déterminer l'impact de l'opération Nez rouge sur la diffusion du concept de "chauffeur délégué" (i.e. une personne du groupe s'engage à ne pas boire pendant une sortie et à ramener les autres). [Table des matières] 1. Questions d'évaluation. 2. Méthodes. 3. Résultats. 3.1. L'enquête "tous-conducteurs" : caractéristiques des répondants (sexe, âge, état d'ébriété), présentation des thèmes (la visibilité de Nez Rouge et la diffusion du concept du chauffeur délégué), la prévention à la Fête des Vignerons (souvenir spontané), perception de la campagne Nez Rouge. 3.2. Comparaison entre les caractéristiques des répondants et des refusants. 3.3. Les rapatriements effectués par Nez Rouge. 3.4. Les actions (itinérantes) de prévention. 4. Recommandations. 5. Questionnaire d'enquête "tous-conducteurs", comparaison du nombre de transports par jour/personnes rapatriées.

Background: Metabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples. Results: Significant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (>= 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p = 0.03). Conclusions: These findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects.