Atypical Antipsychotic-induced Mitochondrial Dysfunction in Patients With Schizophrenia

November 20, 2025 updated by: RITUPARNA MAITI, All India Institute of Medical Sciences, Bhubaneswar

A Randomized Controlled Trial to Evaluate Atypical Antipsychotic-induced Mitochondrial Dysfunction in Patients With Schizophrenia

Schizophrenia is a serious mental disorder with a global prevalence of 1%. The main cause of this condition is dysfunction in the signaling of neurotransmitters dopamine, serotonin, glutamate and Gamma-aminobutyric acid .According to recent research, a disturbed cellular energy state caused by mitochondrial dysfunction is thought to be a factor in the development of schizophrenia.

The aim of the treatment of schizophrenia is to reduce symptoms and is mainly based on the monoamine hypothesis. Atypical antipsychotics are the first-line of treatment.

Certain typical and atypical antipsychotic medications have been shown in prior preclinical research to decrease mitochondrial respiratory chain complex I activity. In contrast to individuals who were drug-naive, Casademont et al. found a significant decrease in complex I activity with haloperidol and risperidone in one cross-sectional observational study. Also, there is evidence suggesting that mitochondrial dysfunction is linked to the extrapyramidal side effects seen with antipsychotics.

To date, there are no randomized controlled trials that assess the effect of these drugs on mitochondrial functions. Hence, the present randomized controlled trial has been planned to evaluate and compare the clinical and biochemical markers of mitochondrial dysfunction in schizophrenia patients treated with the atypical antipsychotics risperidone and aripiprazole.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Odisha
      • Bhubaneswar, Odisha, India, 751019
        • All India Institute Of Medical Sciences (AIIMS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients meeting the DSM-5 criteria for diagnosis of schizophrenia.
  • Treatment naıv̈ e patients or patients who had not taken any antipsychotic drugs for at least 4 weeks before recruitment.
  • Patients of either sex between the ages of 18 and 60 years.
  • Legally authorized representative (LAR) of patients consenting to participate in the study by signing the informed consent form.

Exclusion Criteria:

  • Patients diagnosed with other psychiatric disorders including schizoaffective disorder or schizophrenia with somatoform disorders.
  • Highly agitated patients who need immediate indoor-based treatment.
  • Patients with known mitochondrial disorders (MELAS, LHON, Leigh syndrome, KearnsSayre syndrome, MERRF etc.)
  • Patients with history of comorbidities like cardiovascular, renal, hepatic, neurological, respiratory or endocrinal diseases or malignancies.
  • Patients with history of substance abuse.
  • Pregnant or lactating mothers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aripiprazole group
Aripiprazole will be started at dose of 10 mg/day and increased to a stable dose of 20 mg/day over 2-3 weeks and will be continued till 12 weeks.
Drug: Aripiprazole
Aripiprazole will be started at dose of 10 mg/day and increased to a stable dose of 20 mg/day over 2-3 weeks and will be continued till 12 weeks.
Active Comparator: Risperidone group
Risperidone will be started at dose of 2 mg/day and increased to a stable dose of 6 mg/day over 2-3 weeks and continued till 12 weeks.
Drug: Risperidone
Risperidone will be started at dose of 2 mg/day and increased to a stable dose of 6 mg/day over 2-3 weeks and continued till 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mitochondrial respiratory chain complex I activity/concentration
Time Frame: 12 weeks
Mitochondrial respiratory chain complex I activity/concentration will be measured in platelets using a commercially available ELISA (enzyme-linked immunosorbent assay) kit at baseline and at 12 weeks of follow-up.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum lactate
Time Frame: 12 weeks
Serum lactate will be measured using spectrophotometry at baseline and at 12 weeks follow up
12 weeks
Change in Serum creatine kinase
Time Frame: 12 weeks
Serum creatine kinase will be measured using autoanalyzer at baseline and at 12 weeks
12 weeks
Change in Newcastle Mitochondrial Disease Adult Scale (NMDAS) scores
Time Frame: 12 weeks
Newcastle Mitochondrial Disease Adult Scale (NMDAS) scoring of all patients will be assessed at baseline and at 12 weeks of follow-up. The NMDAS offers a range of 0 to 5 points for each question. The results from each of the first three sections' questions are added together to determine each section's score. The more severe the ailment, the higher the score.
12 weeks
Change in Positive and Negative Syndrome Scale (PANSS) scores
Time Frame: 12 weeks
Positive and Negative Syndrome Scale (PANSS) scoring will be done at baseline and at 12 weeks follow-up. Out of the 30 items included in the PANSS, 7 constitute a Positive Scale, 7 a Negative Scale, and the remaining 16 a General Psychopathology Scale. The scores for these scales are arrived at by summation of ratings across component items. Therefore, the potential ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. The more severe the ailment, the higher the score.
12 weeks
Responder rate
Time Frame: 12 weeks
A patient with a reduction of Positive and Negative Syndrome Scale (PANSS) scores by ≥50% from baseline will be considered a 'responder'..
12 weeks
Change in Serum pyruvate
Time Frame: 12 weeks
Serum pyruvate will be measured using spectrophotometry at baseline and at 12 weeks follow up.
12 weeks
Incidence of treatment-emergent adverse events
Time Frame: 12 weeks
Incidence of treatment-emergent adverse events in both study groups reported throughout the study duration will be reported.
12 weeks
Severity of extrapyramidal adverse effects
Time Frame: 12 weeks
Total score severity of extrapyramidal adverse effects will be assessed by Modified Simpson-Angus Scale. It is a 10-item scale where each item is rated on a 0-4 scale, with higher scores indicating greater severity. The total score is used to gauge the presence and degree of movement disorders, ranging from normal (score<3) to severe (score>12).
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

All India Institute of Medical Sciences, Bhubaneswar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 5, 2024

Primary Completion (Actual)

November 3, 2025

Study Completion (Actual)

November 12, 2025

Study Registration Dates

First Submitted

January 24, 2024

First Submitted That Met QC Criteria

January 24, 2024

First Posted (Actual)

February 1, 2024

Study Record Updates

Last Update Posted (Actual)

November 25, 2025

Last Update Submitted That Met QC Criteria

November 20, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PGThesis/2023-24/100

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) underlying the results of this study will be shared with qualified researchers upon reasonable request. Data will be available after publication and subject to review of a data access proposal and data use agreement.

IPD Sharing Time Frame

Data will be available after publication and will be available for 5 years after publication.

IPD Sharing Access Criteria

Data will be shared with qualified researchers upon reasonable request and subject to review of a data access proposal and data use agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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