Schizophrenia
Conditions
Keywords
Schizophrenia, Mitochondrial electron transport chain complex, Aripiprazole, Risperidone, Mitochondrial dysfunction
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.
Interventions
DRUGAripiprazole
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.
DRUGRisperidone
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.
Sponsors
All India Institute of Medical Sciences, Bhubaneswar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mitochondrial respiratory chain complex I activity/concentration | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum creatine kinase | 12 weeks | Serum creatine kinase will be measured using autoanalyzer at baseline and at 12 weeks |
| Change in Newcastle Mitochondrial Disease Adult Scale (NMDAS) scores | 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. |
| Change in Positive and Negative Syndrome Scale (PANSS) scores | 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. |
| Change in Serum lactate | 12 weeks | Serum lactate will be measured using spectrophotometry at baseline and at 12 weeks follow up |
| Change in Serum pyruvate | 12 weeks | Serum pyruvate will be measured using spectrophotometry at baseline and at 12 weeks follow up. |
| Incidence of treatment-emergent adverse events | 12 weeks | Incidence of treatment-emergent adverse events in both study groups reported throughout the study duration will be reported. |
| Severity of extrapyramidal adverse effects | 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). |
| Responder rate | 12 weeks | A patient with a reduction of Positive and Negative Syndrome Scale (PANSS) scores by ≥50% from baseline will be considered a 'responder'.. |
Countries
India
Outcome results
None listed