Therapeutic Drug Monitoring of Olanzapine: Effects of Clinical Factors on Plasma Concentrations in Psychiatric Patients.

BACKGROUND: Therapeutic drug monitoring (TDM) is strongly recommended for olanzapine due to its high pharmacokinetic variability. This study aimed to investigate the impact of various clinical factors on olanzapine plasma concentrations in patients with psychiatric disorders. METHODS: The study used TDM data from the PsyMetab cohort, including 547 daily dose-normalized, steady-state, olanzapine plasma concentrations (C:D ratios) from 248 patients. Both intrinsic factors (eg, sex, age, body weight) and extrinsic factors (eg, smoking status, comedications, hospitalization) were examined. Univariate and multivariable, linear, mixed-effects models were employed, with a stepwise selection procedure based on Akaike information criterion to identify the relevant covariates. RESULTS: In the multivariable model (based on 440 observations with a complete data set), several significant findings emerged. Olanzapine C:D ratios were significantly lower in smokers (ß = -0.65, P < 0.001), valproate users (ß = -0.53, P = 0.002), and inpatients (ß = -0.20, P = 0.025). Furthermore, the C:D ratios decreased significantly as the time since the last dose increased (ß = -0.040, P < 0.001). The male sex had a significant main effect on olanzapine C:D ratios (ß = -2.80, P < 0.001), with significant interactions with age (ß = 0.025, P < 0.001) and body weight (ß = 0.017, P = 0.011). The selected covariates explained 30.3% of the variation in C:D ratios, with smoking status accounting for 7.7% and sex contributing 6.9%. The overall variation explained by both the fixed and random parts of the model was 67.4%. The model facilitated the prediction of olanzapine C:D ratios based on sex, age, and body weight. CONCLUSIONS: The clinical factors examined in this study, including sex, age, body weight, smoking status, and valproate comedication, remarkably influence olanzapine C:D ratios. Considering these factors, in addition to TDM and the clinical situation, could be important for dose adjustment.

Self-reported caffeine consumption miss-matched consumption measured by plasma levels of caffeine and its metabolites: results from two population-based studies.

IMPORTANCE AND OBJECTIVE: Self-reported caffeine consumption has been widely used in research while it may be subject to bias. We sought to investigate the associations between self-reported caffeine consumption and plasma levels of caffeine and its two main metabolites (paraxanthine and theophylline) in the community. METHODS: Data from two population-based studies (SKIPOGH1 and 2 (N = 1246) and CoLaus|PsyCoLaus (N = 4461)) conducted in Switzerland were used. Self-reported caffeine consumption was assessed using questionnaires. Plasma levels of caffeine and its metabolites were quantified by ultra-high performance liquid chromatography coupled to a tandem quadrupole mass spectrometer. RESULTS: In both studies, mean log plasma levels of caffeine and its two metabolites were over 6.48 (plasma levels = 652 ng/ml) when no caffeine consumption was reported. Subsequently, nonlinear associations between log plasma levels and self-reported caffeine consumption were observed in SKIPOGH, with a change of the slope at 3-5 cups of espresso per day in SKIPOGH1 but not SKIPOGH2. In CoLaus|PsyCoLaus, increased daily consumption of caffeinated beverages was associated with increased log plasma levels with a change of the slope at 3 cups. In both studies, declared caffeine consumption higher than 3-5 cups per day was not associated with higher plasma levels of caffeine and its metabolites. CONCLUSION: Self-reports of no or low caffeine consumption and consumption of more than 3-5 cups of coffee should be interpreted with caution, with possible under- or over-estimation. Quantifying plasma levels of caffeine and its metabolites may contribute to a better estimation of caffeine intake.

Fluctuations in therapist responsiveness facing clients with borderline personality disorder: Starting therapy on the right foot.

OBJECTIVE: The present paper focuses on therapist responsiveness during the initial therapy session with clients with borderline personality disorder (BPD), aiming to analyze therapist responsiveness at short intervals during the initial session and determine if it can predict therapeutic alliance from both therapist and client viewpoints. METHOD: A sample of 47 clients participated in the study for 10 sessions of therapy. Therapeutic alliance from therapists' and clients' perspectives was rated after each session; external raters assessed therapist responsiveness during the initial session. Multiple linear regression models and linear mixed models with backward variable selection based on AIC were run to analyze whether specific therapist behaviors during session one predicted therapeutic alliance rated from therapists' and clients' perspectives. RESULTS: The results indicate that therapists normalizing and validating clients' experiences during the first session are crucial for establishing therapeutic alliance for BPD clients; however, for therapists, the increase in variability of emotions verbalized by clients during the initial session negatively impacts therapeutic alliance. CONCLUSION: The study contributes to further understand the impact of therapists' behavior at the beginning of therapy with BPD clients. Therapist responsiveness is crucial for therapy outcome but is methodologically challenging; therefore, efforts in this direction should be pursued.

Stability of the Subtypes of Major Depressive Disorder in Older Adults and the Influence of Mild Cognitive Impairment on the Stability.

OBJECTIVES: To assess 1) the longitudinal stability of the atypical, melancholic, combined atypical-melancholic and the unspecified subtypes of major depressive disorder (MDD) according to the diagnostic and statistical manual of mental disorders (DSM -IV) specifiers in older adults, and 2) the effect of mild cognitive impairment (MCI) on the stability of these subtypes. DESIGN: Prospective cohort study with a 5.1 year-follow-up. SETTING: Population-based cohort from Lausanne, Switzerland. PARTICIPANTS: A total of 1,888 participants (mean age: 61.7 years, women: 69.2%) with at least two psychiatric evaluations, one after the age of 65 years. MEASUREMENTS: Semistructured diagnostic interview to assess lifetime and 12-month DSM-IV Axis-1 disorders at each investigation and neuro-cognitive tests to identify MCI in participants aged 65 years and over. Associations between lifetime MDD status before and 12-month depression status after the follow-up were assessed using multinomial logistic regression. The effect of MCI on these associations was assessed by testing interactions between MDD subtypes and MCI status. RESULTS: 1) Associations between depression status before and after the follow-up were observed for atypical (adjusted OR [95% CI] = 7.99 [3.13; 20.44]), combined (5.73 [1.50; 21.90]) and unspecified (2.14 [1.15; 3.98]), but not melancholic MDD (3.36 [0.89; 12.69]). However, there was a certain degree of overlap across the subtypes, particularly between melancholic MDD and the other subtypes. 2) No significant interactions were found between MCI and lifetime MDD subtypes regarding depression status after follow-up. CONCLUSION: The strong stability of the atypical subtype in particular highlights the need for identifying this subtype in clinical and research settings, given its well-documented links to inflammatory and metabolic markers.

Do Adult Attachment Style or Personality Mediate the Relationship Between Childhood Maltreatment and Late-Life Depression in Poor Communities?

OBJECTIVE: Childhood maltreatment is associated with late-life depression. Preliminary evidence indicates that personality characteristics, in particular neuroticism and extroversion, and an anxious attachment style mediate this association. The objective is to evaluate 3 models, in which personality and attachment are considered mediators between childhood maltreatment and late-life depression in a socioeconomically disadvantaged Brazilian population. METHODS: This study included participants (n = 260) from socioeconomically disadvantaged neighborhoods of Porto Alegre, Brazil, who completed measures of childhood maltreatment (Childhood Trauma Questionnaire - CTQ), personality characteristics (NEO-Five Factor Inventory), attachment styles (Relationship Scales Questionnaire), and geriatric depression (Mini-International Neuropsychiatric Interview-Plus). General multiple and sequential mediation analyses were used to test for possible associations. RESULTS: Attachment anxiety but not attachment avoidance is a mediator between childhood maltreatment and geriatric depression. Neuroticism is a full mediator. At that, attachment anxiety was found to be a predictor of neuroticism. Finally, sequential mediation analysis shows a path from childhood maltreatment to geriatric depression through attachment anxiety and neuroticism. CONCLUSIONS: The results suggest a pathway from childhood maltreatment to anxious attachment, which in turn predicts higher neuroticism that itself may favor late-life depression. This hypothesis could have implications for older adults living in low socioeconomic settings in that treating the high-risk group of maltreated children may help prevent late-life depression.

Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort.

STUDY OBJECTIVES: 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. METHODS: 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. RESULTS: 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/m2 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. CONCLUSIONS: Insomnia disorders are significantly associated with metabolic worsening and risk of death from cardiovascular diseases in psychiatric patients.

Corrigendum: Relationship Between Effort-Reward Imbalance, Over-Commitment and Occupational Burnout in the General Population: A Prospective Cohort Study.

[This corrects the article DOI: 10.3389/ijph.2023.1606160.].

Associations of Valproate Doses With Weight Gain in Adult Psychiatric Patients: A 1-Year Prospective Cohort Study.

Objective: The aim of this study was to evaluate valproate dose association with weight change, blood glucose, lipid levels, and blood pressure in a psychiatric population.Methods: Data from 215 patients taking valproate for up to 1 year were collected from 2 longitudinal studies that monitored metabolic variables between 2007 and 2022. Linear mixed-effect models and logistic regressions were used to analyze the associations between valproate doses and metabolic outcomes.Results: An increase in valproate dose of 500 mg was associated with a weight change of +0.52% per month over a year (P < .001). The association between valproate dose and weight change was evident both before and after 3 months of treatment. Weight increase was greater for treatment durations of < 3 months compared to ≥ 3 months (+0.56%, P < .001 and +0.12%, P = .02 per month, respectively). Using piecewise regression, a significant association between dose and weight gain was observed in patients receiving doses equal to or above the median dose (1,300 mg/d), with a +0.50% increase in weight for each dose increment of 500 mg (P = .004). Among men, each 500 mg dose increment was associated with weight increases of +0.59% per month (P = .004), whereas a trend was observed for women (+0.40%, P = .09). No associations were found between valproate doses and blood glucose, lipid levels, or blood pressure over a 6-month treatment period.Conclusions: This study provides evidence that valproate dose, mainly for doses at or above 1,300 mg/d, is associated with weight gain in psychiatric patients, suggesting that the lowest effective doses should be prescribed to minimize weight gain.

Mental health and burnout during medical school: Longitudinal evolution and covariates.

BACKGROUND: Medical students' rate of depression, suicidal ideation, anxiety, and burnout have been shown to be higher than those of the same-age general population. However, longitudinal studies spanning the whole course of medical school are scarce and present contradictory findings. This study aims to analyze the longitudinal evolution of mental health and burnout from the first to the last year of medical school using a wide range of indicators. Moreover, biopsychosocial covariates that can influence this evolution are explored. METHOD: In an open cohort study design, 3066 annual questionnaires were filled in by 1595 different students from the first to the sixth year of the Lausanne Medical School (Switzerland). Depression symptoms, suicidal ideation, anxiety symptoms, stress, and burnout were measured along with biopsychosocial covariates. The longitudinal evolution of mental health and burnout and the impact of covariates were modelled with linear mixed models. RESULTS: Comparison to a same-aged general population sample shows that medical students reported significantly more depression symptoms and anxiety symptoms. Medical students' mental health improved during the course of the studies in terms of depression symptoms, suicidal ideation, and stress, although suicidal ideation increased again in the last year and anxiety symptoms remained stable. Conversely, the results regarding burnout globally showed a significant worsening from beginning to end of medical school. The covariates most strongly related to better mental health and less burnout were less emotion-focused coping, more social support, and more satisfaction with health. CONCLUSION: Both improvement of mental health and worsening of burnout were observed during the course of medical school. This underlines that the beginning and the end of medical school bring specific challenges with the first years' stressors negatively impacting mental health and the last year's difficulties negatively impacting burnout.

Self-regulatory control processes in youths: A temporal network analysis approach.

Objective: This study aimed to better understand the temporal interrelationships among self-control, response inhibition, and anger (i.e., momentary state and rumination) on both the within- and between-person levels in male adolescents. Method: We applied temporal network analyses among 62 male adolescents with a wide range of behavioral difficulties. Self-control, momentary anger, and anger rumination were mapped by self-report measures, whereas we measured response inhibition through an ambulatory Go/No-go task (two measures a day-morning and afternoon-over a 9-day period). Results: Temporal network analysis, at the within-person level, revealed that morning measures of response inhibition, anger rumination, and self-control were related to the corresponding measure in the afternoon. More efficient response inhibition in the morning was associated with higher self-control in the afternoon. Higher anger rumination in the morning led to higher momentary anger in the afternoon. In a concurrent within-person network, higher momentary anger was reciprocally associated with lower self-control. At the between-person level, higher momentary anger was correlated to higher anger rumination, lower response inhibition, and lower self-control. Discussion: This study provides insight into the dynamic interactions among self-control, response inhibition, and anger (momentary state and rumination) in male adolescents, advancing the understanding of self-regulatory control functioning.

Metabolic disturbances are risk factors for readmission to psychiatric hospitals in non-smokers but not in smokers: results from a Swiss psychiatric cohort and in first-episode psychosis patients.

Background: Psychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission. Methods: Between 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances. Results: A total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission. Conclusion: The observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk.

Symptom domains and psychosocial functioning in borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is often characterized by severe functional impairment, even after a decrease in symptoms. A comprehensive understanding of psychosocial functioning in BPD is necessary to tailor treatment offer, which should address relevant aspects of daily life. The aims of the present study are to (1) conduct a cross-sectional comparison of functioning of a group with BPD and a non-BPD clinical comparison group at service entry, and to (2) assess the relationship between intensity of BPD symptom domains and psychosocial functioning. METHODS: The sample consists of N = 65 participants with BPD and N = 57 participants from the clinical comparison group without BPD (non-BPD group). The Revised Borderline Follow-up Interview (BFI-R) was used to evaluate psychosocial functioning and the Revised Diagnostic Interview for Borderlines (DIB-R) to assess BPD symptoms. Linear, logistic, and multinomial regression models were run separately for each aspect of functioning as a function of BPD status or BPD symptom domains. RESULTS: Only 23% of participants in the BPD group fulfilled criteria for good overall psychosocial functioning, compared to 53% in the non-BPD group. Furthermore, participants in the BPD group were less likely to have completed a high number of years of education, to work consistently, to be financially independent, to be in a cohabiting relationship and have a good relationship with parents. In addition, various links were identified between BPD symptom domains and functional impairments. CONCLUSIONS: Consistent with prior research, the main impairments in functioning in the BPD group are found in the educational and vocational domains. Though some domains show impairment, others, like friendships, may act as potential resources. Further investigation on the relationships with symptom domains is required.

Aripiprazole dose associations with metabolic adverse effect: Results from a longitudinal study.

OBJECTIVE: Weight gain, blood lipids and/or glucose dysregulation can follow aripiprazole treatment onset. Whether aripiprazole dosage is associated with an increase in these metabolic parameters remains uncertain. The present study investigates aripiprazole dose associations with weight change, blood glucose, lipids, and blood pressure. METHODS: 422 patients taking aripiprazole for a minimum of three weeks to one year were selected from PsyMetab and PsyClin cohorts. Associations between aripiprazole dose and metabolic outcomes were examined using linear mixed-effect models. RESULTS: Aripiprazole dose was associated with weight change when considering its interaction with treatment duration (interaction term: -0.10, p < 0.001). This interaction resulted in greater weight gain for high versus low doses at the beginning of the treatment, this result being overturned at approximately five months, with greater weight increase for low versus high doses thereafter. LDL and HDL cholesterol levels were associated with aripiprazole dose over five months independently of treatment duration, with an average of 0.06 and 0.02 mmol/l increase for each 5 mg increment, respectively (p = 0.033 and p = 0.016, respectively). Furthermore, mean dose increases were associated with greater odds (+30 % per 5 mg increase) of clinically relevant weight gain (i.e., ≥7 %) over one year (p = 0.025). CONCLUSION: Aripiprazole dose was associated with one-year weight changes when considering its interaction with treatment duration. Increasing its dose could lead to metabolic worsening over the first five months of treatment, during which minimum effective doses should be particularly preferred.

Sleep disturbances and incident risk of major depressive disorder in a population-based cohort.

Sleep disturbances are well-known symptoms of major depressive disorder (MDD). However, the prospective risk of MDD in the presence of sleep disturbances in a general population-based cohort is not well known. This study investigated associations between both polysomnography (PSG)-based or subjective sleep features and incident MDD. Participants representative of the general population who had never had MDD completed sleep questionnaires (n = 2000) and/or underwent PSG (n = 717). Over 8 years' follow-up, participants completed psychiatric interviews enabling the diagnosis of MDD. Survival Cox models were used to analyze associations between sleep features and MDD incidence. A higher Epworth Sleepiness Scale and presence of insomnia symptoms were significantly associated with a higher incidence of MDD (hazard ratio [HR] [95 % confidence interval (CI)]: 1.062 [1.022-1.103], p = 0.002 and 1.437 [1.064-1.940], p = 0.018, respectively). Higher density of rapid eye movements in rapid eye movement (REM) sleep was associated with a higher incidence of MDD in men (HR 1.270 [95 % CI 1.064-1.516], p = 0.008). In women, higher delta power spectral density was associated with a lower MDD incidence (HR 0.674 [95 % CI 0.463-0.981], p = 0.039). This study confirmed the associations between subjective and objective sleep features and the incidence of MDD in a large community dwelling cohort.

Using case formulation for prediction of the therapeutic alliance in treatment for borderline personality disorder.

Case formulation is a central tool for psychotherapists, which helps them tailor psychotherapy to the individual patient, particularly for treatments for complex and multilayered clinical problems, such as personality disorders (Kramer, 2019). Case formulation methodologies are still underutilized in psychotherapy research in the prediction of therapy processes. The present study included N = 60 patients with borderline personality disorder undergoing a brief treatment using an individualized treatment component (n = 31), as compared with a standard brief treatment (n = 29; Kramer et al., 2014). For each patient (in both groups as post hoc analysis based on videos), we performed a Plan analysis case formulation (Caspar, 2019): the idiographic information from the formulation was translated into quantitative scores (on a Likert-type scale) assessing patient's interactional agreeableness (vs. antagonism; Zufferey et al., 2019). We modeled the session-by-session predictions of the progression of the therapeutic alliance-rated by the patient and the therapist-over the course of treatment, as a function of interactional agreeableness, the individualization of treatment, as well as their interaction with the session number. Patients with high levels of agreeableness have a significant increase in their alliance assessment over time. Treatment based on the case formulation predicted session-by-session increase of the therapeutic alliance as rated by the therapists. This study was the first to explore intra- and interindividual dynamics of the therapeutic alliance in relationship with idiographic information extracted from case formulations. The results may help understand relationship struggles at the beginning of therapy for complex clinical problems, such as borderline personality disorder. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Relationship Between Effort-Reward Imbalance, Over-Commitment and Occupational Burnout in the General Population: A Prospective Cohort Study.

Objectives: To prospectively investigate the association between Effort-Reward Imbalance (ERI) and over-commitment and the scores of the burnout dimensions over a 4 years follow-up period considering potential confounders. Methods: Data stemmed from CoLaus|PsyCoLaus, a population-based cohort study including 575 participants (mean age 55 years, 50% men). Participants completed the Maslach Burnout Inventory-General Survey, ERI and over-commitment questionnaires at baseline (T1) and after a 4 years follow-up (T2), and provided demographic, behavioral, psychiatric, personality and social support information through self-reported questionnaires and semi-structured interviews. Serially adjusted linear regression models were used. Results: ERI and over-commitment were not associated longitudinally with any of the burnout dimensions when controlling for confounders. One standard deviation increases in the scores of exhaustion, cynicism and professional efficacy were associated with one standard deviation increase in the scores of the same burnout dimensions longitudinally, and these associations were independent of the effects of ERI and over-commitment. Conclusion: Future studies should re-examine the effect of ERI and over-commitment on workers' burnout, considering the effects of confounders.

Evolutions of Metabolic Parameters Following Switches of Psychotropic Drugs: A Longitudinal Cohort Study.

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 < .001, P < .001, and P = .003, respectively). High-to-high or high-to-medium switches resulted in a greater weight increase than switching to lower-risk categories (+0.77% and + 0.39% respectively, P < .001). No difference was found between switching medium-to-medium and medium-to-low (P ≈ 1). Switching high-to-low resulted in 10% weight loss after 2 years, with the greatest loss occurring the first 6 months after the switch. Compared with high-risk controls, lower total cholesterol (-0.27 mmol/l, P = .043) in the high-to-low group, and lower glucose (-0.44 mmol/l, P = .032) and systolic blood pressure (-5.50 mmHg, P = .034) in the low-to-low group were found. Polygenic scores were not associated with weight changes in controls or after switching. CONCLUSION: Psychotropic switches to a lower- or same-risk drug can attenuate weight gain, with only switching high to low resulting in weight loss.

Is Clozapine-induced Weight Gain Dose-dependent? Results From a Prospective Cohort Study.

BACKGROUND: Antipsychotic-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 DESIGN: Linear 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 RESULTS: Each 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. CONCLUSIONS: This 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.

Psychiatric disorders, personality traits, and childhood traumatic events predicting incidence and persistence of chronic pain: results from the CoLaus|PsyCoLaus study.

ABSTRACT: Chronic pain (CP) is often accompanied by mental disorders (MDs). However, little is known concerning the long-term effect of MDs, personality traits, and early-life traumatic events (ETEs) on CP course. Accordingly, we aimed to prospectively assess the associations of major depressive disorders (MDDs), anxiety disorders, personality traits, and ETEs with the incidence and the persistence of CP in middle-aged and older community dwellers. Data stemmed from the 3 first follow-up evaluations of CoLaus|PsyCoLaus, a prospective cohort conducted in the general population of Lausanne (Switzerland). Diagnostic criteria for MDs and ETEs were elicited using semistructured interviews. CP and personality traits were assessed by self-rating questionnaires. Follow-up intervals were subdivided into 2 groups: those without (n = 2280) and those with (n = 1841) CP initially. The associations between the psychological variables and the occurrence or persistence of CP 5 years later were assessed using serially adjusted logistic regression models. Higher neuroticism (odds ratio [95% confidence interval] 1.21 [1.08; 1.36]) and extraversion (1.18 [1.06; 1.32]) were associated with higher 5-year CP incidence, whereas current (2.14 [1.34; 3.44]) and remitted MDD (1.29 [1.00; 1.66]) as well as lower extraversion (0.83 [0.74; 0.94]) were associated with persistence of CP. By contrast, ETEs and anxiety disorders were not associated with the incidence or persistence of CP. Our results suggest that personality traits are associated with both CP occurrence and persistence, whereas the MDDs may be more associated with CP persistence. Both personality and MDD are accessible to psychotherapy, and MDD is also accessible to pharmacotherapy. Hence, these therapeutic measures might decrease the risk of CP and its persistence.