Clozapine: Improvement of Negative Symptoms of Schizophrenia

We report five cases of treatment-resistant schizophrenia that presented with prominent negative and positive symptoms. They fulfill the criteria of diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). They showed lack of response despite receiving multiple trials of first and second generation psychotropic agents. We decided to give these patients a trial of clozapine to improve their negative and positive symptoms as well as their quality of life. The patients showed various responses to the treatment. Two patients had a robust response to clozapine, two had a moderate response, and treatment was discontinued for one patient due to a side effect of eosinophilia with clozapine, with an eosinophil count increased to 40,000/mm3 (40%). Clozapine has been established to be more beneficial than conventional antipsychotics in patients with treatment-resistant schizophrenia and apparently more useful, based on existing evidence, in managing the negative symptoms of schizophrenia. We suspect that the improvement in negative symptoms will be associated with an improvement in positive symptoms as well as the compound has a direct action on neuronal pathways responsible for the negative symptoms. Five treatment-refractory schizophrenic patients were given a trial of clozapine for 24 weeks and observed. Overall, two patients showed modest improvement in psychotic and negative symptoms including insight and judgment improvement in disorganization. Two patients demonstrated robust response with significant improvement in negative symptoms including insight, judgment, affect, avolition, and disorganization and also an improvement in psychotic symptoms. We monitored complete blood chemistry (CBC) including the absolute neutrophil count on a weekly basis. Before initiation of the treatment, four patients had all the routine labs performed including glycated hemoglobin (HbA1C), thyroid panel, CBC, comprehensive metabolic panel and fasting lipid profile; all were within normal reference ranges. One patient had type 2 diabetes mellitus (DM) for the past eight years, and his HbA1c was 6.7; that remained stable through the treatment. We managed the symptoms of his type 2 DM with oral hypoglycemic agents and long-acting insulin to control blood sugar and performed a yearly urine analysis for proteinuria to monitor organ damage. His other routine labs were within normal range.