Metabolic Side-effects of Anti-psychotic Medications - a Nested Case Control Cohort Historical Prospective Study

Study Overview
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Brief Summary
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The study is designed to fill in the gaps in current knowledge by providing a more inclusive and comprehensive understanding of the potential associations between antipsychotics (APs) and negative outcomes, as previous research has often been limited to data from clinical trials. The primary objectives of the study include assessing the association between APs and long-term major negative events such as osteoporosis, acute myocardial infarction, stroke, tardive dyskinesia, chronic obstructive pulmonary disease and breast cancer. Additionally, the study aims to assess the association between APs and long-term negative metabolic events such as diabetes, obesity, hypertension and hypercholesterolemia. The study also aims to assess the association between APs and long-term negative metabolic measurements such as increased body mass index, cholesterol levels, triglyceride levels, Hemoglobin A1C levels and glucose levels. This study aims to investigate the potential long-term negative effects of APs on patients with schizophrenia and schizoaffective disorders by using data from the Clalit Health Services database, which is the largest provider of health insurance in Israel, serving approximately 55% of the population. This database provides access to all diagnoses and blood tests for the duration of the study, which allows for accurate tracking of patient outcomes over time. Inclusion criteria for patients include being diagnosed with schizophrenia or schizoaffective disorder in the Clalit database, having first exposure to AP medication between the ages of 18-60, having first prescription of AP medication between 2001 and 2021, and will follow them using the CHS database to assess metabolic side-effects and the appearance of major negative and major metabolic events, as well as abnormal metabolic measurements. The preliminary analysis of the study used a sample of 22,777 patients diagnosed with schizophrenia or schizoaffective disorder between the years 2001-2021 in the Clalit dataset. This sample was used to assess whether patients who received at any time clozapine, olanzapine, and quetiapine had a higher risk of major negative and metabolic events. The analysis found that patients who received these medications were at a higher risk of developing metabolic outcomes and most major negative events. Based on these findings, the study aims to have a sample size large enough to detect these associations and allow for meaningful conclusions to be drawn from the data.

Official Title
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Metabolic Side-effects of Anti-psychotic Medications - a Nested Case Control Cohort Historical Prospective Study

Conditions
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Psychotic Disorders

Intervention / Treatment
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* Drug: Antipsychotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Schizophrenia and schizoaffective disorder patients: Diagnosed with schizophrenia or schizoaffective disorder in the Clalit database. First exposure to AP medication between the ages of 18-60 First prescription of AP medication between 2001-2021, hence at baseline (at 2000) were not receiving anti-psychotics Exposed to AP medications for at least 6 months. Control individuals: Not diagnosed with schizophrenia, schizoaffective disorder or bi-polar disorder. Never prescribed AP medication. Matched for age, sex and socio-economic status. Exclusion Criteria: Individuals not meeting the inclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Schizophrenia and schizoaffective disorder patients<br>Diagnosed with schizophrenia or schizoaffective disorder in the Clalit database. First exposure to AP medication between the ages of 18-60 First prescription of AP medication between 2001-2021, hence at baseline (at 2000) were not receiving anti-psychotics Exposed to AP medications for at least 6 months. | Drug: Antipsychotic<br>* Receiving any antipsychotic agent<br>|
| Control individuals<br>Not diagnosed with schizophrenia, schizoaffective disorder or bi-polar disorder. Never prescribed AP medication. Matched for age, sex and socio-economic status. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term major negative events | Report in national database of MI, OCPD, Breast cancer, Tardive dyskinesia, Stroke, Osteoporosis. The database includes a list of reported diseases and major health events, with a score of 0 for no report and a score of 1 for diagnosis of disease. A diagnosis will be considered positive if it appears for at least two years. | During follow-up from 2000 to 2021 | 
| Long-term metabolic events | Diagnosis of Diabetes, Obesity, Hypercholesterolemia, Hypertension. A diagnosis will be considered positive if it appears for at least two years. A composite score will be defined as the appearance of a diagnosis of one or more of the following: diabetes, obesity, hypertension, hypercholesterolemia and hypertriglyceridemia. | During follow-up from 2000 to 2021 | 
| Long-term metabolic measurements- BMI | BMI report- using metric units (weight in km/square of height in meters) | During follow-up from 2000 to 2021 | 
| Long-term metabolic measurements- Cholesterol levels | Report of cholesterol levels measured in millimoles per liter (mmol/L) | During follow-up from 2000 to 2021 | 
| Long-term metabolic measurements- Triglycerides levels | Report of triglyceride levels measured in millimoles per liter (mmol/L) | During follow-up from 2000 to 2021 | 
| Long-term metabolic measurements- HbA1C levels | Report of glycated hemoglobin (HbA1C) levels measured in millimoles per moles (mmol/mol) | During follow-up from 2000 to 2021 | 
| Long-term metabolic measurements- glucose levels | Report of glucose levels measured in millimoles per liter (mmol/L) | During follow-up from 2000 to 2021 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antipsychotics, Side effects, Metabolic