Differential effect of quetiapine on depressive symptoms in patients with partially responsive schizophrenia. Effects of sulpiride and chlorpromazine on depressive symptoms in schizophrenic patients--relationship to drug concentrations.
While atypical antipsychotics appear to be effective in reducing depressive symptoms in the acute phase of schizophrenia, little is known about their efficacy in patients with ongoing symptoms. The present study assessed whether quetiapine (Seroquel) is more effective than haloperidol in treating depressive symptoms in patients with persistent positive symptoms, and investigated whether this effect is independent, or secondary to, reductions in other symptoms such as positive, negative or extrapyramidal symptoms. Patients with schizophrenia and a history of partial refractoriness to conventional antipsychotics who had not responded to 4 weeks of fluphenazine treatment (20 mg/day) were randomized to receive either quetiapine (600 mg/day) or haloperidol (20 mg/day) for a further 8 weeks. Change in the Positive and Negative Syndrome Scale depression factor score from baseline to endpoint was calculated and path analyses were performed on data from 269 patients. Quetiapine produced a greater reduction in depressive scores than haloperidol (-1.60 versus -0.54; p = 0.006). The path analyses indicated that this was a direct effect on depressive symptoms. These findings extend the evidence for an antidepressant effect for the novel antipsychotics in schizophrenia, and suggest that this is not limited to acutely psychotic patients. Schizophrenic patients were treated with fixed doses of sulpiride (800 mg/day) or chlorpromazine (CPZ) (400 mg/day) over a period of 8 weeks using a double-blind design. There were 25 patients in each group and all the patients were in an acute phase of their disease. They all fulfilled the Research Diagnostic Criteria (RDC) for schizophrenia. Depressive symptoms as rated according to the Comprehensive Psychopathological Rating Scale (CPRS) were present in the patients before treatment was started. The depressive and psychotic symptoms in both groups decreased in parallel during the whole period of treatment. Patients in the sulpiride group recovered more quickly from depressive symptoms than patients in the CPZ group. It was also found that patients with low concentrations of sulpiride or CPZ in serum recovered more completely from depressive symptoms and had fewer extrapyramidal side effects than patients with high drug concentrations.
There are too few data to guide patients, carers, clinicians or policy makers. Current practice has to be guided by evidence other than that derived from randomised trials and more trials in this important area are indicated.