Side Effects of Psychiatric Medications - a Nested Case Control Cohort Historical Prospective Study

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 different psychiatric medications, including antipsychotics (APs), Antidepressants, Benzodiazepines and mood stabilizers, 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 different psychiatric medications and long-term major negative medical conditions and events. Additionally, the study aims to assess the association between different psychiatric medications and long-term negative metabolic events such as diabetes, obesity, hypertension and hypercholesterolemia.

This study aims to investigate the potential long-term negative effects of different psychiatric medications on patients with schizophrenia, schizoaffective disorder, depression, bipolar disorder and dementia, patients with other diagnoses, as well as patients receiving different psychiatric medications who do not have a psychiatric diagnosis. The study will be done using data from the Clalit Health Services (CHS) 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 include being diagnosed with schizophrenia/schizoaffective disorder/bipolar disorder/depression, dementia, other psychiatric diagnoses, and/or patients receiving these medications who do not have a psychiatric diagnosis, and use psychiatric medications, including antipsychotics/antidepressants/mood stabilizers/benzodiazepines as registered in the Clalit database. having first prescription of psychiatric medication between 2001 and 2024. The study will look at those patients included and will follow them using the CHS database to assess these different medical and or metabolic side-effects and the appearance of major negative and major metabolic events, as well as abnormal metabolic measurements.

Study Overview

• Status: Active, not recruiting
• Conditions: Psychotic Disorders
• Intervention / Treatment: Drug: Psychiatric Drugs

Detailed Description

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 different psychiatric medications, including antipsychotics (APs), Antidepressants, Benzodiazepines and mood stabilizers, 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 different psychiatric medications and long-term major negative events such as cancer, osteoporosis, hip fracture, acute myocardial infarction, stroke, tardive dyskinesia, chronic obstructive pulmonary disease, chronic kidney failure and dialysis. Additionally, the study aims to assess the association between different psychiatric medications and long-term negative metabolic events such as diabetes, obesity, hypertension and hypercholesterolemia The study also aims to assess the association between different psychiatric medications and long-term negative metabolic measurements such as increased body mass index, cholesterol levels, triglyceride levels, Hemoglobin A1C levels and glucose levels, hyperprolactinemia, as well as low eGFR.

This study aims to investigate the potential long-term negative effects of different psychiatric medications on patients with schizophrenia, schizoaffective disorder, depression, bipolar disorder and dementia, patients with other diagnoses, as well as patients receiving different psychiatric medications who do not have a psychiatric diagnosis. The study will be done using data from the Clalit Health Services (CHS) 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 include being diagnosed with schizophrenia/schizoaffective disorder/bipolar disorder/depression, dementia, other psychiatric diagnoses, and/or patients receiving these medications who do not have a psychiatric diagnosis, and use psychiatric medications, including antipsychotics/antidepressants/mood stabilizers/benzodiazepines as registered in the Clalit database. having first prescription of psychiatric medication between 2001 and 2024. The study will look at those patients included and will follow them using the CHS database to assess these different medical and or 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.

• Study Type: Observational
• Enrollment (Estimated): 22777

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel
    • Sheba Medical Center, Psychiatry Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Inclusion criteria for patients include being diagnosed with schizophrenia/schizoaffective disorder/bipolar disorder/depression/other psychiatric diagnoses, and will also include patients receiving these medications who do not have a psychiatric diagnosis. Using psychiatric medications including antipsychotics/antidepressants/mood stabilizers/benzodiazepines as registered in the Clalit database. The study will look at those patients included and will follow them using the CHS database to assess different medical side-effects and the appearance of major negative and major metabolic events, as well as abnormal metabolic measurements.

Psychiatric diagnoses by ICD 10 are included if assigned by a psychiatrist or registered following hospital discharge. The validity of these diagnoses has been verified in previous studies (Bieber et al., 2013).

Description

Inclusion Criteria:

Study Group:

1. Diagnosed with schizophrenia/schizoaffective disorder/bipolar disorder/depression/dementia/diagnosed with other psychiatric disorders, or not diagnoses with any disorder, and registered in the Clalit database.
2. First exposure to antipsychotics/antidepressants/benzodiazepines/mood stabilizers above the age of 16 years, regardless of the presence of having a psychiatric diagnosis. We will include patients treated with these medications also if they do not have a psychiatric diagnosis.
3. Prescription of these psychiatric medications between 2001-2024

Control Group:

1. The control groups will differ according to the analysis performed, and will be clearly described in the publication.
2. Depending on the analysis, will not include person prescribed antipsychotics, antidepressants, benzodiazepines, mood stabilizers.
3. Matched for age, sex and socio-economic status and other potential confounders, depending on the disease studied.

Exclusion Criteria:

• Individuals not meeting the inclusion criteria.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with psychiatric diagnosis/prescribed psychiatric medications; Diagnosed with schizophrenia/schizoaffective disorder/bipolar disorder/depression/dementia/diagnosed with other psychiatric disorders, or not diagnoses with any disorder, and registered in the Clalit database.; First exposure to antipsychotics/antidepressants/benzodiazepines/mood stabilizers above the age of 16 years, regardless of the presence of having a psychiatric diagnosis. We will include patients treated with these medications also if they do not have a psychiatric diagnosis.; Prescription of these psychiatric medications between 2001-2024	Drug: Psychiatric Drugs; Receiving any Antipsychotic, Benzodiazepine, antidepressant, mood stabilizer; Other Names: Antipsychotics, Benzodiazepines, antidepressants, mood stabilizers
Control individuals; The control groups will differ according to the analysis performed, and will be clearly described in the publication.; Depending on the analysis, will not include person prescribed antipsychotics, antidepressants, benzodiazepines, mood stabilizers.; Matched for age, sex and socio-economic status and other potential confounders, depending on the disease studied.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Long-term major negative events	Report in national database of cancer, heart disease (heart failure, MI), lung disease (COPD), Tardive dyskinesia, Neurological conditions (CVA, TIA, Epilepsy), , Osteoporosis, hip fracture, chronic kidney disease and dialysis. 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.	During follow-up from 2000 to 2021

Collaborators and Investigators

• Sponsor: Mark Weiser, MD, Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: May 9, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Metabolic; Antipsychotics; Side effects
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antipsychotic Agents
• Other Study ID Numbers: 0277-23-SMC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No