The antipsychotic drug clozapine is associated with weight gain. The proposed mechanisms include blocking of serotonin (5‐HT2a/2c), dopamine (D2) and histamine (H1) receptors. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2) to norclozapine, a metabolite with more 5‐HT2c‐receptor and less H1 blocking capacity. We hypothesized that norclozapine serum levels correlate with body mass index (BMI), waist circumference and other parameters of the metabolic syndrome. We performed a retrospective cross‐sectional study in 39 patients (female n = 8 (20.5%), smokers n = 18 (46.2%), average age 45.8 ± 9.9 years) of a clozapine outpatient clinic in the Netherlands between 1 January 2017 and 1 July 2020. Norclozapine concentrations correlated with waist circumference (r = 0.354, P = .03) and hemoglobin A1c (HbA1c) (r = 0.34, P = .03). In smokers (smoking induces CYP1A2), norclozapine concentrations correlated with waist circumference (r = 0.723, P = .001), HbA1c (r = 0.49, P = .04) and BMI (r = 0.63, P = .004). Elucidating the relationship between norclozapine and adverse effects of clozapine use offers perspectives for interventions and treatment options.

Background Approximately one-third of all patients with schizophrenia are treatment resistant. Worldwide, undertreatment with clozapine and other effective treatment options exist for people with treatment-resistant schizophrenia (TRS). In this respect, it appears that regular health care models do not optimally fit this patient group. The Collaborative Care (CC) model has proven to be effective for patients with severe mental illness, both in primary care and in specialized mental health care facilities. The key principles of the CC model are that both patients and informal caregivers are part of the treatment team, that a structured treatment plan is put in place with planned evaluations by the team, and that the treatment approach is multidisciplinary in nature and uses evidence-based interventions. We developed a tailored CC program for patients with TRS. Objective In this paper, we provide an overview of the research design for a potential study that seeks to gain insight into both the process of implementation and the preliminary effects of the CC program for patients with TRS. Moreover, we aim to gain insight into the experiences of professionals, patients, and informal caregivers with the program. Methods This study will be underpinned by a multiple case study design (N=20) that uses a mixed methods approach. These case studies will focus on an Early Psychosis Intervention Team and 2 Flexible Assertive Community treatment teams in the Netherlands. Data will be collected from patient records as well as through questionnaires, individual interviews, and focus groups. Patient recruitment commenced from October 2020. Results Recruitment of participants commenced from October 2020, with the aim of enrolling 20 patients over 2 years. Data collection will be completed by the end of 2023, and the results will be published once all data are available for reporting. Conclusions The research design, framed within the process of developing and testing innovative interventions, is discussed in line with the aims of the study. The limitations in clinical practice and specific consequences of this study are explained. International Registered Report Identifier (IRRID) DERR1-10.2196/35336

UNSTRUCTURED Background Around one-third of all patients with schizophrenia are classified as "treatment-resistant". Across the globe, there is under-treatment with clozapine and other effective treatment options for people with treatment-resistant schizophrenia (TRS). In this respect, it appears that regular healthcare models do not optimally fit this particular patient group. The Collaborative Care model (CC) has proven to be effective for patients with severe mental illness, both in primary care and in specialized mental healthcare facilities. The key principles of the CC model is that both patients and informal caregivers are part of the treatment team, that a structured treatment plan is put in place with planned evaluations by the team, and that the treatment approach is both multidisciplinary in nature and uses evidence-based interventions. We have developed a tailored CC-program for patients with TRS (CC-TRS). In this paper, we provide an overview of the research design for a potential study that seeks to gain insight into both the process of implementation and the preliminary effects of CC-TRS. Moreover, we will aim to gain insight into the experiences of professionals, patients and informal caregivers with the program. Methods The study will be underpinned by a multiple case-study design (N = 20) that utilizes a mixed-methods approach. These case studies will focus on one Early Intervention in Psychosis Team (EIT) and two Flexible Assertive Community treatment (FACT) teams in the Netherlands. Data will be collected from patients’ records as well as through questionnaires, individual interviews and focus groups. We began the process of recruiting patients in October 2020. Discussion The research design is discussed in line with the aims of the study, which are framed within the process of developing and testing innovative interventions. The limitations in clinical practice as well as their specific consequences for this study are explained. Trial registration AsPredicted (#62738), pre-registration titled 'Collaborative care for patients with treatment-resistant schizophrenia', registered 13 April 2021. https://aspredicted.org/gk958.pdf.