Atypical Antipsychotics Influence on the Safety of the Heart and Monitoring Indicators Model Building

The purpose of this study was to investigate the effect of atypical antipsychotics on cardiac safety. The secondary purpose was to understand the rate of QTc prolongation in electrocardiogram induced by atypical antipsychotics. And try to construct the model of cardiac monitoring index. We conducted a randomized trial in which patients with schizophrenia who were first on or off medication for more than two weeks took a single atypical antipsychotic (Risperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine) for 12 weeks and monitored changes in biochemical, electrocardiogram and other indicators. And then 50 patients with adverse cardiac reactions (ADRs) taking antipsychotics were selected to review the data, analyze and construct a monitoring model.

We hypothesized that atypical antipsychotics with different mechanisms of action have different effects on cardiac safety in patients with schizophrenia, and that they are applicable to different populations. The monitoring index model can reduce the occurrence of cardiotoxicity and improve the prognosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Risperidone; Drug: Aripiprazole; Drug: Ziprasidone; Drug: Amisulpride; Drug: Quetiapine

Detailed Description

Atypical antipsychotics, also known as new antipsychotics, are a group of drugs that act on the central nervous system to treat schizophrenia, psychotic disorder or bipolar disorder. Compared with typical antipsychotics, atypical antipsychotics have the advantages of good efficacy and fewer side effects. Therefore, currently, atypical antipsychotics are widely used in clinical practice. In recent years, the effects of atypical antipsychotics on metabolism and cardiovascular system have attracted more and more clinical attention. Studies have found that long-term use of atypical antipsychotics can lead to arrhythmias, drug-induced myocarditis, and even cardiac arrest. Since antipsychotics can cause cardiac adverse events in patients with schizophrenia, accompanied by medical complications, resulting in a generally shorter life span of 15-25 years compared with the general population, cardiac safety assessment of drugs for patients with schizophrenia is becoming increasingly important. But the domestic study of antipsychotics in the cardiovascular field, especially about the safety of heart systemic evaluation are few and far between, so this research has focused on patients with schizophrenia in China people use different mechanisms of atypical antipsychotics (Risperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine) on heart safety.

In the first stage, a total of 350 schizophrenia patients were enrolled who were either not on medication for the first time or stopped for more than 2 weeks. They were treated with atypical antipsychotics respectively, follow-up of 12 weeks, evaluating the effects of antipsychotics on cardiac function and structure in patients with schizophrenia from general data, biochemistry, electrocardiogram, etc. In the second stage, 50 patients of adverse cardiac reactions caused by taking antipsychotics were selected from enrolled subjects, and a retrospective analysis(day1, week4, week12, and week24) was conducted to try to build a cardiac safety detection indicator model, so as to understand the impact of antipsychotics on cardiac safety. More rational use of antipsychotics in the context of ensuring clinical efficacy and minimum side effects, and the use of monitoring indicator models to reduce the occurrence of cardiac toxicity, improve the safety of antipsychotics in use.

• Study Type: Interventional
• Enrollment (Anticipated): 350
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: LV QINYU; Phone Number: 18017311158; Email: 18616550357@163.com
• Study Contact Backup: Name: YI ZHENGHUI; Phone Number: 18017311007; Email: yizhenghui1971@163.com

Study Locations

• China
  • Minhang
    • Shanghai, Minhang, China, 201108
      • China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Phase one:Effects of different types of atypical antipsychotics on cardiac safety.

  1. Meet the diagnostic of "schizophrenia" according to DSM-IV and fail to take medication in the first episode or stop taking medication for more than 2 weeks
  2. Han ethnic, 18-45 years old;
  3. Exclude persons with mental disorders caused by organic diseases, drugs or alcohol, and other mental disorders, and serious suicide attempts.
  4. Willing to participate in the trial and receive treatment;
  5. Course of disease within 2 years;
  6. Able to communicate effectively with the researcher and complete the written informed consent signed by hand.

Phase two:Construction of cardiac safety monitoring model

1. Meet the diagnostic of "schizophrenia" according to DSM-IV and fail to take medication in the first episode or stop taking medication for more than 2 weeks
2. Han ethnic, 18-45 years old;
3. Exclude persons with mental disorders caused by organic diseases, drugs or alcohol, and other mental disorders, and serious suicide attempts.
4. Willing to participate in the trial and receive treatment;
5. Serious arrhythmia, myocarditis, cardiomyopathy and cardiac insufficiency during taking medicine;
6. Able to communicate effectively with the researcher and complete the written informed consent signed by hand.

Exclusion Criteria:

• (1) Participating in other clinical studies; (2) Combination of DSM-IV diagnoses other than schizophrenia; (3) History of heart disease; (4) History of drug abuse in the previous 6 months; (5) Pregnant or in the first three months of lactation; (6) Combination of antipsychotics, mood stabilizers and antidepressants was used in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Risperidone; Risperidone tablet	Drug: Risperidone; Use medicine according to patients condition
Experimental: Aripiprazole; Aripiprazole tablet	Drug: Aripiprazole; Use medicine according to patients condition
Experimental: Ziprasidone; Ziprasidone tablet	Drug: Ziprasidone; Use medicine according to patients condition
Experimental: Amisulpride; Amisulpride tablet	Drug: Amisulpride; Use medicine according to patients condition
Experimental: Quetiapine; Quetiapine tablet	Drug: Quetiapine; Use medicine according to patients condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac QTc(corrected QT interval) interphase changes after drug administration.	Cardiac QTc interphase changes during the study duration	baseline, week2,4, 8, 12，24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical index： BNP(Brain Natriuretic Peptide)	Changes of biochemical indexes during the study duration	baseline, week2,4, 8, 12，24
Biochemical index：troponin	Changes of biochemical indexes during the study duration	baseline, week2,4, 8, 12，24
Biochemical index： myoglobin	Changes of biochemical indexes during the study duration	baseline, week2,4, 8, 12，24
Electrocardiogram：Heart rate	Changes of ECG indicators during the study duration	baseline, week2,4, 8, 12，24
Echocardiographic: EF(Ejection Fraction) value	Changes of cardiac ultrasound indicators during the study duration	baseline, week2,4, 8, 12，24

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 26, 2020
• Last Update Submitted That Met QC Criteria: August 25, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Atypical antipsychotics; Cardiac safety; Model building
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Antidepressive Agents, Second-Generation; Aripiprazole; Quetiapine Fumarate; Risperidone; Ziprasidone; Amisulpride
• Other Study ID Numbers: YG2019QNB07

Drug and device information, study documents

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