Vitamin C as an adjunct to Antipsychotics after failed trial of a single Antipsychotic in Patients with Schizophrenia and its Correlation with Malondialdehyde: An open Label Study

Schizophrenia is a chronic, disabling psychiatric disorder affecting approximately 1 percent of the population, with high suicide risk and poor functional outcomes. It presents with positive symptoms like hallucinations and delusions, negative symptoms such as apathy and social withdrawal, and significant cognitive impairments. Despite treatment, about 40 to 50 percent of patients show inadequate response to a single antipsychotic, and around 30 percent progress to treatment resistant schizophrenia i.e., TRS, where clozapine remains the gold standard despite its serious and sometimes fatal side effects. Antipsychotics are notably ineffective in addressing negative and cognitive symptoms, highlighting the need for safer adjunctive therapies. Oxidative stress has been implicated in the pathophysiology of schizophrenia, as evidenced by elevated malondialdehyde, MDA levels and diminished antioxidants like glutathione and vitamin C, with the brain s high oxidative load making it especially vulnerable to reactive oxygen species induced neuronal damage. Vitamin C, a potent antioxidant, not only protects against oxidative stress but also supports neurotransmitter synthesis, particularly dopamine, which is central to schizophrenia s pathology. Preliminary research suggests that vitamin C supplementation may improve psychiatric symptoms and oxidative profiles in schizophrenia patients. This study proposes to evaluate the efficacy of vitamin C,1000 mg per day as an adjunctive therapy alongside antipsychotics in patients who have failed a previous antipsychotic trial. Conducted as a six week, open label, hospital based study at the Central Institute of Psychiatry, the trial will randomize 60 inpatients into two groups, with and without vitamin C. Clinical outcomes will be measured using CGI SCH, PANSS, SAPS, SANS, and MoCA at baseline, three weeks, and six weeks, while blood levels of MDA and ascorbic acid will be assessed to correlate biochemical and clinical changes. Validated clinical rating tools and ELISA based biochemical assays will be employed. If vitamin C proves effective, it could represent a low risk, accessible adjunctive option to enhance both clinical and biochemical outcomes in schizophrenia management.