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NCT Number: NCT06236451

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.

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Key information

Conditions

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

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

All India Institute of Medical Sciences (AIIMS)

Bhubaneswar, Odisha, 751019, India

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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.

Primary outcomes

  1. 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.

Secondary outcomes

  1. Change in Serum lactate

    Time frame: 12 weeks

    Serum lactate will be measured using spectrophotometry at baseline and at 12 weeks follow up

  2. Change in Serum creatine kinase

    Time frame: 12 weeks

    Serum creatine kinase will be measured using autoanalyzer at baseline and at 12 weeks

  3. 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.

  4. 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.

  5. 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'..

  6. Change in Serum pyruvate

    Time frame: 12 weeks

    Serum pyruvate will be measured using spectrophotometry at baseline and at 12 weeks follow up.

  7. 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.

  8. 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).

Sponsors and collaborators

Lead sponsor

All India Institute of Medical Sciences, Bhubaneswar

Other

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Feb 1, 2024
Registry last updated
Nov 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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