Atypical Antipsychotic-induced Mitochondrial Dysfunction in Patients With Schizophrenia

NCT ID: NCT06236451

Last Updated: 2025-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-05

Study Completion Date

2025-11-12

Brief Summary

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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.

Detailed Description

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Conditions

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Schizophrenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Aripiprazole

Intervention Type 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.

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.

Group Type ACTIVE_COMPARATOR

Risperidone

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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All India Institute of Medical Sciences, Bhubaneswar

OTHER

Sponsor Role lead

Responsible Party

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RITUPARNA MAITI

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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All India Institute of Medical Sciences (AIIMS)

Bhubaneswar, Odisha, India

Site Status

Countries

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India

References

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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.

Reference Type RESULT
PMID: 37175697 (View on PubMed)

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.

Reference Type RESULT
PMID: 16801664 (View on PubMed)

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.

Reference Type RESULT
PMID: 17287825 (View on PubMed)

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.

Reference Type RESULT
PMID: 22215558 (View on PubMed)

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.

Reference Type RESULT
PMID: 37528429 (View on PubMed)

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.

Reference Type RESULT
PMID: 34365585 (View on PubMed)

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.

Reference Type RESULT
PMID: 14661862 (View on PubMed)

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.

Reference Type RESULT
PMID: 26953070 (View on PubMed)

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.

Reference Type RESULT
PMID: 17502776 (View on PubMed)

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.

Reference Type RESULT
PMID: 25446950 (View on PubMed)

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.

Reference Type DERIVED
PMID: 41093357 (View on PubMed)

Other Identifiers

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PGThesis/2023-24/100

Identifier Type: -

Identifier Source: org_study_id

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