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BackgroundAntipsychotic-induced metabolic adverse effects are risk factors for cardiometabolic comorbidities. Whether dose lowering could mitigate such effects remains unclear. The present study aims to investigate the associations between clozapine doses and modifications of weight, blood pressure, blood glucose, and lipid levels.Study DesignLinear mixed-effects models of weight changes over 1 year and of variations of other metabolic parameters over 4 months were applied to a prospective cohort of 115 patients. Age- and sex-stratified analyses of weight changes were also performed.Study ResultsEach 100 mg dose increment of clozapine was associated on average with a +0.48% weight increase (P = .004) over 1 year of treatment. Weight increase was greater for treatment duration ≤3 vs >3 months (+0.84% and +0.47% per month, respectively, P < .001), with a significant association with the dose for durations >3 months (+0.54%, P = .004) and a trend for durations ≤3 months (+0.33%, P = .075). Dose increments of 100 mg were also associated with weight increases of +0.71% among adults (P = .001), +1.91% among the elderly (P < .001) and +1.32% among men (P < .001) with no associations among women (P = .62). Among young adults, weight change was positively associated with doses ≤300 mg/day (+2.19% per 100 mg, P = .001), whereas no association was found with doses >300 mg/day (P = .60). No significant effect of clozapine dose on other metabolic parameters was found.ConclusionsThis study reports a modest effect of clozapine dose increases on weight gain over 1 year with differences among age categories and sexes and no dose effect on other metabolic parameters over 4 months.

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.

European archives of psychiatry and clinical neuroscience (2022). doi:10.1007/s00406-022-01542-1, Published by Steinkopff, Darmstadt

Cases of addictions and misuses on gabapentinoids are increasingly reported. But the underlying pharmacological mechanism is not completely understood. Here is an uptodate of the current knowledges on this dependence and its management.Des cas de mésusages et d’addictions aux gabapentinoïdes sont de plus en plus fréquemment rapportés, sans que le mécanisme pharmacologique sous-jacent ne soit complètement compris. Nous faisons un état des lieux des connaissances sur cette dépendance et sa prise en charge.

The management of patients who have become dependent on benzodiazepines and analogues is a problem frequently encountered in both somatic and psychiatric medicine. No pharmacological treatment is currently recognized as effective in the management of these addictions, apart from a gradual reduction of doses. We propose practical strategies for the implementation of gradual dose reduction and choice of molecules while promoting individual adaptation to the withdrawal symptoms presented by the patient.La prise en charge de patients ayant développé une dépendance aux benzodiazépines et analogues est une problématique rencontrée fréquemment tant en médecine somatique que psychiatrique. Aucun traitement pharmacologique n’est actuellement reconnu comme efficace dans la prise en charge de ces dépendances, en dehors d’une réduction progressive des doses. Nous proposons des stratégies pratiques de mise en œuvre de réduction progressive des doses et de choix de molécules tout en favorisant une adaptation individuelle aux symptômes de sevrage présentés par le patient.

Confronted with a complaint of insomnia, several points must be considered before prescribing a specific treatment. In particular, it is necessary to optimize the management of somatic and psychiatric comorbidities that can affect sleep and to review the intake of sleep-disrupting substances and drugs. The current guidelines for insomnia rank treatment options based on the quality of the evidence. They all agree to recommend cognitive behavioural therapy for insomnia as first-line treatment. Pharmacological treatment should only be considered if this therapy fails. We then propose to start with the drugs presenting the best safety profile before prescribing, if necessary, those having better effectiveness evidence but carrying a greater risk of side effects.Face à une plainte d’insomnie, plusieurs points sont à prendre en compte avant d’envisager un traitement spécifique, notamment l’optimisation de la prise en charge des comorbidités somatiques et psychiatriques pouvant péjorer le sommeil et la revue de la prise de substances et médicaments le perturbant. Les recommandations sur l’insomnie classent les options thérapeutiques selon la qualité des études à disposition. Elles s’accordent toutes à recommander la thérapie cognitivo-comportementale spécifique pour l’insomnie en première intention. Un traitement pharmacologique ne devrait être envisagé qu’en cas d’échec de cette thérapie. Nous proposons alors de débuter avec les molécules présentant le meilleur profil de sécurité avant de passer, si nécessaire, à celles ayant mieux démontré leur efficacité mais comportant un plus grand risque d’effets secondaires.

Association of selected SNP with systolic blood pressure in the general control Kazakh cohort. (DOCX 13Â kb)

Allele frequency and genotype distribution in the general Kazakh cohorts. (DOCX 50Â kb)

Association of candidate SNP loci with type 2 diabetes in the general Kazakh study cohorts. (DOCX 15Â kb)

Association of selected SNP with low-density lipoprotein in the general control Kazakh cohort. (DOCX 13Â kb)

Association of selected SNP with high-density lipoprotein in the general control Kazakh cohort. (DOCX 13Â kb)

Association of candidate SNP with obesity in the general control Kazakh cohort. (DOCX 15Â kb)

Association of selected SNP with cholesterol in the general control Kazakh cohort. (DOCX 12Â kb)

Association of selected SNP with BMI in the general control Kazakh cohort. (DOCX 12Â kb)

INTRODUÇÃO: O efeito do envelhecimento nas concentrações plasmáticas em estado de equilíbrio da paroxetina foi investigado em 136 pacientes com depressão, tratados com doses variando entre 10 e 120 mg/dia de paroxetina. MÉTODOS: Os pacientes foram separados em três grupos: com idade até 64 anos (idade média ± desvio padrão: 41,7±12,6 anos; n = 44), entre 65 e 79 anos (72,8±4,7 anos; n = 64), e com mais de 80 anos (82,8±3,3 anos; n = 28). As doses de paroxetina foram normalizadas para 20 mg/dia. Amostras de sangue foram coletadas em condições de estado de equilíbrio. Os níveis plasmáticos de paroxetina foram medidos por cromatografia gasosa - espectrometria de massa. As funções hepática e renal foram medidas por testes laboratoriais clínicos estandardizados. RESULTADOS: Uma grande variabilidade interindividual dos níveis plasmáticos de paroxetina (37 vezes) foi medida para uma mesma dose. A média dos níveis plasmáticos de paroxetina corrigida para uma dose diária de 20 mg foi 87% maior no grupo com mais de 80 anos (56,4±64,1 ng/mL; p < 0,05) e 57% maior no grupo com idades entre 65 e 79 anos (46,7±33,4 ng/mL; p < 0,001) quando comparada com a média dos pacientes com menos de 64 anos (29,9±11,9 ng/mL). A idade foi correlacionada significativamente com os níveis plasmáticos de paroxetina (r = 0,21, p < 0,05) CONCLUSÃO: A redução de doses da paroxetina em pacientes idosos parece justificada.INTRODUCTION: The effect of aging on steady-state plasma concentrations of paroxetine was investigated in 136 depressive patients treated with paroxetine 10-120 mg/day. METHODS: The patients were divided into three groups: aged up to 64 years (mean age ± standard deviation: 41.7±12.6 years; n = 44), between 65 and 79 years (72.8±4.7 years; n = 64), and 80 years or older (82.8±3.3 years; n = 28). Paroxetine doses were normalized to 20 mg/day. Blood samples were collected under steady-state conditions. Paroxetine plasma levels were measured by gas chromatography/mass spectrometry. Hepatic and renal functions were measured by standardized clinical laboratory tests. RESULTS: A large interindividual variability of paroxetine plasma levels (37-fold) was measured for a given dose. The mean plasma levels of paroxetine corrected for a 20 mg daily dose were 87% higher in the very elderly (≥ 80 years) patients (56.4±64.1 ng/mL; p < 0.05) and 57% higher in the elderly (65-79 years) patients (46.7±33.4 ng/mL; p < 0.001) when compared to the adult patients (< 64 years) (29.9±11.9ng/mL). Age correlated significantly with paroxetine plasma levels (r = 0.21, p < 0.05). CONCLUSION: Recommended dose reduction of paroxetine in elderly patients seems therefore justified.

Risk of developing at least three components of the metabolic syndrome in the general unmatched Kazakh cohort. (DOCX 15Â kb)

Risk of developing at least three components of the metabolic syndrome in the general unmatched Kazakh cohort. (DOCX 15Â kb)