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Introduction: Adequate antipsychotic treatment intensity is required before diagnosing resistant schizophrenia and initiating clozapine treatment. We aimed to investigate potential rapid drug metabolism underlying low dose-adjusted serum concentration (CD) of non-clozapine atypical antipsychotics preceding clozapine treatment. Methods: Patients using non-clozapine, atypical antipsychotics (aripiprazole, risperidone, olanzapine, or quetiapine) within 1 year before starting clozapine were included in this study from a therapeutic drug monitoring service in Oslo, Norway, between 2005 and 2023. Patients were assigned into low CD (LCD) and normal CD (NCD) subgroups. Using a reference sample with 147,964 antipsychotic measurements, LCD was defined as CDs below the 25th percentile, while patients with NCD exhibited CDs between the 25th and 75th percentile of the respective reference measurements. Metabolic ratios, doses, and frequency of subtherapeutic levels of non-clozapine antipsychotics were compared between LCD and NCD groups. Results: Preceding clozapine treatment, 110 out of 272 included patients (40.4%) were identified with LCD. Compared with the NCD group, LCD patients exhibited higher metabolic ratios of olanzapine (1.5-fold; p < 0.001), quetiapine (3.0-fold; p < 0.001), and risperidone (6.0-fold; p < 0.001). Metabolic ratio differences were independent of smoking and CYP2D6 genotype for olanzapine (p = 0.008) and risperidone (p = 0.016), respectively. Despite higher doses of olanzapine (1.25-fold; p = 0.054) and quetiapine (1.6-fold; p = 0.001) in LCD versus NCD patients, faster metabolism among the former was accompanied by higher frequencies of subtherapeutic levels of olanzapine (3.3-fold; p = 0.044) and quetiapine (1.8-fold; p = 0.005). Conclusion: LCD and associated rapid metabolism of non-clozapine antipsychotics is frequent before starting clozapine treatment. For olanzapine and quetiapine, this is associated with significantly increased risk of having subtherapeutic concentrations. [ABSTRACT FROM AUTHOR]

Objectives Bipolar disorder ( BD), over the long term, can manifest a variety of outcomes depending on a number of different conditions. There is a need for further knowledge regarding preventive factors as well as predictors of the disabling course of the disorder. Studies regarding the impact on functional outcome of premorbid and current general intellectual function [intelligence quotient ( IQ)] and premorbid functioning in BD patients are sparse. The present study addressed the role of premorbid functioning [assessed with the Premorbid Adjustment Scale ( PAS)], intelligence, course of illness, and sociodemographics on occupational outcome in BD. Methods Bipolar disorder patients were recruited consecutively from psychiatric units (outpatient and inpatient) in four major hospitals in Oslo, Norway [(N = 226: 64.4% bipolar I disorder ( BD-I); 30.1% bipolar II disorder ( BD- II); 5.5% bipolar disorder not otherwise specified ( BD- NOS); 38.6% males]. The associations between current IQ, premorbid IQ [assessed using the National Adult Reading Test ( NART)], PAS, clinical and sociodemographic characteristics, and receipt of disability benefit were analysed using descriptive statistics and logistic regression analyses. Results The number of hospitalizations for depressive episodes and illness duration was associated with a higher risk of receipt of disability benefit. PAS, premorbid and current IQ, as well as decline in IQ, did not explain the higher risk of receipt of disability benefits. Conclusions Severe clinical course of BD was associated with receipt of disability benefit. Occupational outcome was unrelated to PAS, premorbid and current IQ, as well as decline in IQ. This suggests that the persistence of severe clinical symptoms, rather than global cognitive functioning, determines occupational outcome in BD and emphasizes the protective potential of early and continuous clinical treatment. [ABSTRACT FROM AUTHOR]

Background: There is a strong association between bipolar disorder (BD) and substance use disorder (SUD). The clinical and functional correlates of SUD in BD are still unclear and little is known about the role of excessive substance use that does not meet SUD criteria. Thus, the aims of the current study were to investigate lifetime rates of illicit substance use in BD relative to the normal population and if there are differences in clinical and functional features between BD patients with and without excessive substance use. Methods: 125 consecutively recruited BD in- and outpatients from the Oslo University Hospitals and 327 persons randomly drawn from the population in Oslo, Norway participated. Clinical and functional variables were assessed. Excessive substance use was defined as DSM-IV SUD and/or excessive use according to predefined criteria. Results: The rate of lifetime illicit substance use was significantly higher among patients compared to the reference population (OR = 3.03, CI = 1.9-4.8, p < .001). Patients with excessive substance use (45% of total) had poorer educational level, occupational status, GAF-scores and medication compliance, with a trend towards higher suicidality rates, compared to patients without. There were no significant group differences in current symptom levels or disease course between groups. Conclusion: The percentage of patients with BD that had tried illicit substances was significantly higher than in the normal population. BD patients with excessive substance use clearly had impaired functioning, but not a worse course of illness compared to patients without excessive substance use. An assessment of substance use beyond SUD criteria in BD is clinically relevant. [ABSTRACT FROM AUTHOR]

Highlights • Use of antipsychotics was significantly associated with both L/A ratio and HOMA-IR. • Antipsychotics and HOMA-IR were associated both independently and via L/A ratio. • These associations remained significant when BMI was adjusted for. • Olanzapine and aripiprazole displayed significant effects on HOMA-IR via L/A ratio. Abstract Background The prevalence of obesity, metabolic syndrome and type 2 diabetes mellitus is increased among patients with severe mental disorders, and particularly use of second generation antipsychotic drugs is associated with metabolic side effects. Antipsychotics have been found to alter levels of adipokines which regulate insulin sensitivity, but their role in antipsychotic-associated insulin resistance is not established, and it is unclear whether adipokines affect insulin resistance independently of body mass index (BMI). Methods We included 1050 patients with severe mental disorders and 112 healthy controls aged 18–65 years from the Oslo area, Norway. Clinical variables, BMI and use of medication were assessed, fasting blood samples were obtained for calculation of the leptin/adiponectin ratio (L/A ratio) and estimate of insulin resistance using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Case-control analyses were followed by mediation analyses to evaluate the possible direct effect of antipsychotics on HOMA-IR and indirect effect mediated via the L/A ratio. This was performed both with and without adjustment for BMI, in the total sample and in an antipsychotic monotherapy subsample (N = 387). Results BMI, L/A ratio and HOMA-IR were significantly higher in patients than controls (p < 0.001-p = 0.01). There was a significant direct effect from use of antipsychotics in general on HOMA-IR both without (b = 0.03, p = 0.007) and with adjustment for BMI (b = 0.03, p = 0.013), as well as a significant mediating effect via L/A ratio both without (b = 0.03, p < 0.001) and with adjustment for BMI (b = 0.01, p = 0.041). Use of olanzapine (b = 0.03, p < 0.001) or aripiprazole (b = 0.04, p < 0.001) in monotherapy showed significant effects on HOMA-IR mediated via L/A ratio. Conclusions The study suggests that use of antipsychotics may alter adipokine levels, and that increased L/A ratio may play a role in the development of insulin resistance associated with use of antipsychotics also independently of BMI. [ABSTRACT FROM AUTHOR]