Reposicionamento de fármacos no tratamento da esquizofrenia: um estudo duplo-cego, randomizado, de ácido alfa-lipoico em baixas doses

Abstract

Schizophrenia can be a very impairing mental disorder, mainly due to the intellectual, interpersonal, emotional, and social impairments that encompass the so-called negative symptoms. However, even though treatment with dopamine D2 receptor blockers is effective for psychotic symptoms, there is a clinical gap with regard to the pharmacological management of negative symptoms. Given the preclinical evidence that there is a low level of endogenous antioxidants and a high level of reactive oxygen species in patients with schizophrenia, several drugs for the relief of negative symptoms have been investigated under this theoretical basis. Here we report the results of a randomized, double-blind, placebo-controlled translational study to evaluate the clinical response of patients with schizophrenia receiving adjuvant treatment with alpha-lipoic acid 100 mg/day, compared to the adjuvant use of placebo, for sixteen weeks. Our goal was to evaluate whether there would be changes in: negative and positive symptoms, assessed using the Brief Psychiatric Rating Scale (BPRS); cognitive functioning, observed through a standardized neuropsychological assessment; extrapyramidal symptoms, assessed by the Simpson-Angus Scale; body mass index; and a series of oxidative/inflammatory parameters, with comparisons between the placebo and treatment groups. Continuous antipsychotic medications were maintained according to each patient's usual medical prescription. 48 people between eighteen and sixty years old (32 men and 16 women) were included, of which 35 (23 men and 12 women) completed the study protocol. We found no significant improvement in body mass index, cognition, clinical symptoms of schizophrenia, antipsychotic adverse effects, or markers of oxidative stress and inflammation in the intervention group compared to the placebo group. However, the entire group of patients (intervention and placebo groups, taken together) improved in several aspects, indicating a strong placebo effect in this population. A surprising finding was a significant decrease in the alpha-lipoic acid treated group’s red blood cells, white blood cells, and platelets. This decrease in red blood cell, white blood cell, and platelet counts requires further investigation. It suggests that more attention is needed when prescribing alpha-lipoic acid to patients with schizophrenia.