A Randomized Controlled Trial to Evaluate Atypical Antipsychotic-induced Mitochondrial Dysfunction in Patients With Schizophrenia
Overview
- Phase
- Phase 4
- Intervention
- Aripiprazole
- Conditions
- Schizophrenia
- Sponsor
- All India Institute of Medical Sciences, Bhubaneswar
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Change in Mitochondrial respiratory chain complex I activity/concentration
- Status
- Completed
- Last Updated
- 5 months ago
Overview
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.
Investigators
RITUPARNA MAITI
Professor
All India Institute of Medical Sciences, Bhubaneswar
Eligibility Criteria
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.
Arms & Interventions
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.
Intervention: Aripiprazole
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.
Intervention: Risperidone
Outcomes
Primary Outcomes
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
- 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)
- Change in Serum pyruvate(12 weeks)
- Incidence of treatment-emergent adverse events(12 weeks)
- Severity of extrapyramidal adverse effects(12 weeks)