Who is at risk for weight gain after weight-gain associated treatment with antipsychotics, antidepressants, and mood stabilizers: A machine learning approach.

BACKGROUND: Weight gain is a common side effect in psychopharmacology; however, targeted therapeutic interventions and prevention strategies are currently absent in day-to-day clinical practice. To promote the development of such strategies, the identification of factors indicative of patients at risk is essential. METHODS: In this study, we developed a transdiagnostic model using and comparing decision tree classifiers, logistic regression, XGboost, and a support vector machine to predict weight gain of ≥5% of body weight during the first 4 weeks of treatment with psychotropic drugs associated with weight gain in 103 psychiatric inpatients. We included established variables from the literature as well as an extended set with additional clinical variables and questionnaires. RESULTS: Baseline BMI, premorbid BMI, and age are known risk factors and were confirmed by our models. Additionally, waist circumference has emerged as a new and significant risk factor. Eating behavior next to blood glucose were found as additional potential predictor that may underlie therapeutic interventions and could be used for preventive strategies in a cohort at risk for psychotropics induced weight gain (PIWG). CONCLUSION: Our models validate existing findings and further uncover previously unknown modifiable factors, such as eating behavior and blood glucose, which can be used as targets for preventive strategies. These findings underscore the imperative for continued research in this domain to establish effective preventive measures for individuals undergoing psychotropic drug treatments.

Edema related to treatment with psychotropic drugs.

Edema as an adverse drug reaction is a commonly underestimated yet potentially debilitating condition. This study analyzes the incidence of severe psychotropic drug-induced edema (e.g., edema affecting the face, legs, or multiple body parts and lasting for more than 1 week, or in any case necessitating subsequent diuretic use) among psychiatric inpatients. The cases under examination are derived from an observational pharmacovigilance program conducted in German-speaking countries ("Arzneimittelsicherheit in der Psychiatrie", AMSP) from 1993 to 2016. Among the 462,661 inpatients monitored, severe edema was reported in 231 cases, resulting in an incidence of 0.05%. Edema occurred more frequently in women (80% of all cases) and older patients (mean age 51.8 years). Pregabalin had the highest incidence of severe edema, affecting 1.46‰ of patients treated with pregabalin, followed by mirtazapine (0.8‰). The majority of edema cases showed a positive response to appropriate countermeasures, such as dose reduction and drug discontinuation, and resolved by the end of the observation period. While most instances of drug-induced edema are reversible, they can have a significant impact on patient well-being and potentially result in decreased treatment adherence. It is, therefore, crucial to remain vigilant regarding risk-increasing circumstances during treatment with psychotropic drugs.

Deconstructing depression by machine learning: the POKAL-PSY study.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621).

Antipsychotic drug-induced neutropenia: results from the AMSP drug surveillance program between 1993 and 2016.

Neutropenia and agranulocytosis (N&A) are relatively rare, but potentially fatal adverse drug reactions (ADR). This study presents cases of N&A related to one or more antipsychotic drugs (APDs) in psychiatric inpatients. Data on APD utilization and reports of N&A caused by APDs were analyzed by using data from an observational pharmacovigilance program in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP)-from 1993 to 2016. 333,175 psychiatric inpatients were treated with APDs for schizophrenia and other indications during the observation period. A total of 124 cases of APD-induced N&A were documented, 48 of which fulfilled the criteria for agranulocytosis, corresponding to a rate of 0.37, respectively, 0.14 in 1000 inpatients treated with APDs. Neutropenia was more often detected in women, whereas there was no difference regarding sex in cases of agranulocytosis. Clozapine had the highest relative risk for inducing N&A and was imputed alone as a probable cause of N&A in 60 cases (1.57‰ of all patients exposed). Perazine showed the second highest relative risk with 8 cases and an incidence 0.52‰, followed by quetiapine (15 cases resp. 0.23‰ of all patients exposed) and olanzapine (7 cases; 0.13‰ of all patients exposed). N&A most often occurred during the first 3 months of treatment. Overall N&A are severe and potentially fatal complications that can occur during treatment with APDs. The results from this study largely agree with the currently available literature, highlighting the positive effects of alertness and established appropriate monitoring.

Lifestyle behaviors, metabolic disturbances, and weight gain in psychiatric inpatients treated with weight gain-associated medication.

Many psychiatric patients suffer from overweight/obesity and subsequent metabolic disturbances, where psychotropic medication is one of the main contributors. However, the magnitude of weight gain ranges individually, which leads to questioning the role of other contributors like lifestyle factors. The present study investigated several lifestyle factors among psychiatric inpatients, their relation to biological factors, and their predictive capability for weight gain during treatment. Using a naturalistic observational study design, psychiatric inpatients of all diagnoses were followed for 4 weeks from the start of treatment with weight gain-associated medication. N = 163 participants entered the study. Lifestyle factors were assessed by patient self-report questionnaires. Body weight change over time was calculated relative to baseline body weight. Our study provides three main findings: (1) Obesity and/or metabolic syndrome (metSy) were associated with emotional eating (disinhibition), craving for fast food and sweets, and weight cycling. (2) Patients without metSy and normal BMI experienced increased sweets craving (also for women), a more positive attitude towards drugs, and an improvement of affect (also for men). (3) Sex, presence of metSy and/or drug dosage interacted with disinhibition change, sweets craving change (trend), and fast food craving change to predict weight change over time. Furthermore, drug attitude change interacted with BMI, drug dosage, and presence of metSy to predict weight change. Lifestyle factors, especially eating behaviors, are related to metabolic disturbances and predict weight gain in interaction with clinical parameters.

A comprehensive approach to predicting weight gain and therapy response in psychopharmacologically treated major depressed patients: A cohort study protocol.

BACKGROUND: A subgroup of patients with Major Depressive Disorder shows signs of low-grade inflammation and metabolic abberances, while antidepressants can induce weight gain and subsequent metabolic disorders, and lacking antidepressant response is associated with inflammation. OBJECTIVES: A comprehensive investigation of patient phenotypes and their predictive capability for weight gain and treatment response after psychotropic treatment will be performed. The following factors will be analyzed: inflammatory and metabolic markers, gut microbiome composition, lifestyle indicators (eating behavior, physical activity, chronotype, patient characteristics (childhood adversity among others), and polygenic risk scores. METHODS: Psychiatric inpatients with at least moderate Major Depressive Disorder will be enrolled in a prospective, observational, naturalistic, monocentric study using stratified sampling. Ethical approval was obtained. Primary outcomes at 4 weeks will be percent weight change and symptom score change on the Montgomery Asberg Depression Rating Scale. Both outcomes will also be binarized into clinically relevant outcomes at 5% weight gain and 50% symptom score reduction. Predictors for weight gain and treatment response will be tested using multiple hierachical regression for continuous outcomes, and multiple binary logistic regression for binarized outcomes. Psychotropic premedication, current medication, eating behavior, baseline BMI, age, and sex will be included as covariates. Further, a comprehensive analysis will be carried out using machine learning. Polygenic risk scores will be added in a second step to estimate the additional variance explained by genetic markers. Sample size calculation yielded a total amount of N = 171 subjects. DISCUSSION: Patient and physician expectancies regarding the primary outcomes and non-random sampling may affect internal validity and external validity, respectively. Through the prospective and naturalistic design, results will gain relevance to clinical practice. Examining the predictive value of patient profiles for weight gain and treatment response during pharmacotherapy will allow for targeted adjustments before and concomitantly to the start of treatment.

Atypical dyskinesias under treatment with antipsychotic drugs: Report from the AMSP multicenter drug safety project.

OBJECTIVES: The aim of this study was to describe atypical dyskinesias (AtypDs) occurring during treatment with antipsychotic drugs (APDs). AtypDs are dyskinesias showing either an unusual temporal relationship between onset of treatment and start of the adverse drug reaction (ADR) or an unusual presentation of clinical symptoms. METHODS: Data on the utilisation of APDs and reports of severe APD-induced AtypDs were collected using data from the observational pharmacovigilance programme - 'Arzneimittelsicherheit in der Psychiatrie (English: drug safety in psychiatry)' (AMSP) - from 1993 to 2016. RESULTS: A total of 495,615 patients were monitored, of which 333,175 were treated with APDs. Sixty-seven cases (0.020%) of severe AtypDs under treatment with APDs were registered. The diagnoses of schizophrenic disorders as well as organic mental disorders were related to significantly higher rates of AtypDs. Second-generation antipsychotic drugs (SGAs) showed slightly higher rates of AtypDs (0.024%) than high-potency (0.011%) or low-potency first-generation antipsychotic drugs (FGAs; 0.006%). In 41 cases (61.2%), two or more drugs were found to cause AtypDs. CONCLUSIONS: Our study indicates that AtypDs are rare ADRs. SGAs may have a higher risk for the occurrence of AtypDs than FGAs. Clinicians should be aware of this ADR and patients should be monitored and examined carefully.

A case series of serious and unexpected adverse drug reactions under treatment with cariprazine.

Reporting of new or unexpected adverse drug reactions of medicines that are subject to additional monitoring ("black triangle" label), such as the antipsychotic drug cariprazine, is of paramount importance to improve pharmacotherapy safety.

Content validity of the comprehensive international classification of functioning, disability and health (ICF) core set for low back pain from the perspective of physicians: a Delphi survey.

OBJECTIVES: The 'Comprehensive ICF Core Set for low back pain (LBP)' is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning of patients with LBP. The objective of this study was to validate this ICF Core Set from the perspective of physicians. METHODS: Physicians experienced in the treatment of LBP were asked about the patients' problems, patients' resources and aspects of environment that physicians take care of in a three-round survey using the Delphi technique. Responses were linked to the ICF. RESULTS: Seventy-one physicians in 36 countries named 707 concepts that covered all ICF components. One hundred ninety-three ICF categories were linked to these answers. Three ICF categories were not represented in the Comprehensive ICF Core Set for LBP although at least 75% of the participants have rated them as important. Twenty-six concepts were linked to the not yet developed ICF component personal factors and 21 issues were not covered by the ICF. DISCUSSION: The high percentage of ICF categories represented in the ICF Core Set for LBP indicates good content validity from the perspective of the physicians. However, some issues were raised that were not covered and need to be investigated further.