Atypical Antipsychotic-induced Mitochondrial Dysfunction in Patients With Schizophrenia

NCT06236451 | Completed Phase 4

• 1 other identifier: PGThesis/2023-24/100
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia

Keywords

Schizophrenia; Mitochondrial electron transport chain complex; Aripiprazole; Risperidone; Mitochondrial dysfunction

Outcome Measures

Primary Outcomes (1)

• Change in Mitochondrial respiratory chain complex I activity/concentration

  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 Outcomes (8)

• Change in Serum lactate

  12 weeks

• Change in Serum creatine kinase

  12 weeks

• Change in Newcastle Mitochondrial Disease Adult Scale (NMDAS) scores

  12 weeks

• Change in Positive and Negative Syndrome Scale (PANSS) scores

  12 weeks

• Responder rate

  12 weeks

Study Arms (2)

Aripiprazole group

EXPERIMENTAL

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

Risperidone group

ACTIVE COMPARATOR

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

Interventions

Aripiprazole DRUG

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.

Aripiprazole group

Risperidone DRUG

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.

Risperidone group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

All India Institute of Medical Sciences (AIIMS)

Bhubaneswar, Odisha, 751019, India

Location

Related Publications (11)

• Hardy RE, Chung I, Yu Y, Loh SHY, Morone N, Soleilhavoup C, Travaglio M, Serreli R, Panman L, Cain K, Hirst J, Martins LM, MacFarlane M, Pryde KR. The antipsychotic medications aripiprazole, brexpiprazole and cariprazine are off-target respiratory chain complex I inhibitors. Biol Direct. 2023 Aug 1;18(1):43. doi: 10.1186/s13062-023-00375-9.

  PMID: 37528429 RESULT

• Luptak M, Fisar Z, Hroudova J. Effect of Novel Antipsychotics on Energy Metabolism - In Vitro Study in Pig Brain Mitochondria. Mol Neurobiol. 2021 Nov;58(11):5548-5563. doi: 10.1007/s12035-021-02498-4. Epub 2021 Aug 8.

  PMID: 34365585 RESULT

• Modica-Napolitano JS, Lagace CJ, Brennan WA, Aprille JR. Differential effects of typical and atypical neuroleptics on mitochondrial function in vitro. Arch Pharm Res. 2003 Nov;26(11):951-9. doi: 10.1007/BF02980205.

  PMID: 14661862 RESULT

• Scaini G, Rochi N, Morais MO, Maggi DD, De-Nes BT, Quevedo J, Streck EL. In vitro effect of antipsychotics on brain energy metabolism parameters in the brain of rats. Acta Neuropsychiatr. 2013 Feb;25(1):18-26. doi: 10.1111/j.1601-5215.2012.00650.x.

  PMID: 26953070 RESULT

• Casademont J, Garrabou G, Miro O, Lopez S, Pons A, Bernardo M, Cardellach F. Neuroleptic treatment effect on mitochondrial electron transport chain: peripheral blood mononuclear cells analysis in psychotic patients. J Clin Psychopharmacol. 2007 Jun;27(3):284-8. doi: 10.1097/JCP.0b013e318054753e.

  PMID: 17502776 RESULT

• Rajasekaran A, Venkatasubramanian G, Berk M, Debnath M. Mitochondrial dysfunction in schizophrenia: pathways, mechanisms and implications. Neurosci Biobehav Rev. 2015 Jan;48:10-21. doi: 10.1016/j.neubiorev.2014.11.005. Epub 2014 Nov 15.

  PMID: 25446950 RESULT

• Fizikova I, Dragasek J, Racay P. Mitochondrial Dysfunction, Altered Mitochondrial Oxygen, and Energy Metabolism Associated with the Pathogenesis of Schizophrenia. Int J Mol Sci. 2023 Apr 28;24(9):7991. doi: 10.3390/ijms24097991.

  PMID: 37175697 RESULT

• Schaefer AM, Phoenix C, Elson JL, McFarland R, Chinnery PF, Turnbull DM. Mitochondrial disease in adults: a scale to monitor progression and treatment. Neurology. 2006 Jun 27;66(12):1932-4. doi: 10.1212/01.wnl.0000219759.72195.41.

  PMID: 16801664 RESULT

• Leucht S, Davis JM, Engel RR, Kane JM, Wagenpfeil S. Defining 'response' in antipsychotic drug trials: recommendations for the use of scale-derived cutoffs. Neuropsychopharmacology. 2007 Sep;32(9):1903-10. doi: 10.1038/sj.npp.1301325. Epub 2007 Feb 7.

  PMID: 17287825 RESULT

• Venegas V, Halberg MC. Measurement of mitochondrial DNA copy number. Methods Mol Biol. 2012;837:327-35. doi: 10.1007/978-1-61779-504-6_22.

  PMID: 22215558 RESULT

• Shaju A, Mohapatra D, Mishra BR, Mishra A, Srinivasan A, Maiti R. Evaluation of atypical antipsychotic-induced mitochondrial dysfunction in patients with schizophrenia: a randomised controlled trial protocol. BMJ Open. 2025 Oct 15;15(10):e098173. doi: 10.1136/bmjopen-2024-098173.

  PMID: 41093357 DERIVED

MeSH Terms

Conditions

Schizophrenia; Mitochondrial Diseases

Interventions

Aripiprazole; Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrimidinones; Pyrimidines

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 24, 2024
• First Posted: February 1, 2024
• Study Start: April 5, 2024
• Primary Completion: November 3, 2025
• Study Completion: November 12, 2025
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available after publication and will be available for 5 years after publication.
• 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.

Locations

IN (1)