Pregnenolone improved functional capacity in participants with schizophrenia, but did not improve cognitive symptoms over an 8-week treatment period. Neurosteroid changes correlated with functional improvements in female participants. Neurosteroid interventions may exhibit promise as new therapeutic leads for schizophrenia.

Background: Atypical antipsychotics are widely prescribed, yet have been associated with weight gain and metabolic syndrome. Aim: To study the effect of adjunct low-dose aripiprazole on weight and metabolic parameters of subjects on atypical antipsychotics (olanzapine, clozapine or risperidone). Methods: The study was carried out as an open-label trial with a fixed dose of 5 mg aripiprazole added to the patient’s current antipsychotic for 12 weeks. The primary outcome measure was mean change in weight, while secondary outcome measures included change in waist circumference; fasting blood glucose; HbA1c; triglycerides; total, HDL and LDL cholesterol levels; functioning; and neurocognition. Results: For the overall study ( n = 55), there was no significant effect of adjunct aripiprazole on the weight of the subjects. However, the clozapine group achieved significant weight loss ( p = 0.002) and also had significant improvements in total cholesterol ( p < 0.001), HDL ( p = 0.016), LDL ( p = 0.044) and triglyceride levels ( p = 0.038). The olanzapine group had significant improvement in triglycerides ( p = 0.001), and other metabolic parameters for this group showed improvement trends, but did not reach statistical significance. The risperidone group did not show any significant improvement in weight or metabolic parameters. Conclusions: The study adds support to the adjunctive use of aripiprazole to clozapine for weight loss and improvement in metabolic profile, and for reduction in cardiometabolic risk for patients on olanzapine. Trial Registration: Clinicaltrials.gov identifier: NCT02949752

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Bipolar affective disorder is characterized by recurring episodes of mania with or without, but commonly with, episodes of depression. It usually begins in adolescence and can cause enduring and substantial impairment if left untreated. It needs a long-term treatment with mood stabilizers to prevent relapses. Elevated or depressed mood relapses can be either primary or secondary. However, primary mood relapses can occur without a significant precipitating factor, more often tending to occur following stressful life events or discontinuation of mood stabilizer medications. Secondary mood relapses can be caused by many conditions, such as physical illnesses, substance misuse and medications. When a mental illness coexists with another physical illness and the treatment of one complicates the other, it adds complexity to the selection of appropriate pharmacological regime for either condition. In this paper, the authors present a case of bipolar affective disorder who had two episodes of mania likely precipitated by methotrexate, which were reversed by the withdrawal of the offending drug (methotrexate). To the best of the authors’ knowledge, to date there have been no published reports in the literature in which methotrexate, an immunosuppressive and a cytotoxic drug, precipitated a manic episode in a patient with bipolar affective disorder.

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