Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta) in patients with schizophrenia.

Thirteen patients with schizophrenia received injections of 25, 50, or 75 mg of long-acting risperidone every 2 wk. Brain D2 receptor occupancy was assessed with [11C]raclopride 2 wk after the last (fifth) injection (day 71) in seven subjects and 2 wk after the third injection (day 44) in one subject. Stable plasma concentrations were reached after the third injection and steady-state concentrations of the active moiety (risperidone + 9-hydroxyrisperidone) after the fourth injection. Steady-state plasma concentrations were maintained for 4-5 wk after the last injection and then declined rapidly. After injections of 25, 50 and 75 mg on day 44 or day 71, D2 receptor occupancy ranged from 25-48%, 59-83% and 62-72% respectively, while plasma active-moiety levels ranged from 4.4-8.8, 15.0-31.1 and 22.5-26.3 ng/ml respectively. The results indicate that brain D2 receptor occupancy at steady state after injections of long-acting risperidone was in the range found in patients effectively treated with 2-6 mg of oral risperidone.

Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic.

BACKGROUND: The long-term safety and efficacy of long-acting injectable risperidone, the first long-acting second-generation antipsychotic, were evaluated in stable patients with schizophrenia. METHOD: After a 2-week run-in period during which patients with DSM-IV schizophrenia received flexible doses of 1 to 6 mg of oral risperidone, patients received injections of 25 mg, 50 mg, or 75 mg of long-acting risperidone every 2 weeks for 12 months. Severity of extrapyramidal symptoms was assessed with the Extrapyramidal Symptom Rating Scale (ESRS), and efficacy was assessed with the Positive and Negative Syndrome Scale (PANSS). This study was conducted from March 29, 1999 to July 19, 2000. RESULTS: The subjects were 615 patients with schizophrenia who received at least 1 injection of long-acting risperidone. The 12-month trial was completed by 65% of patients. Treatment was discontinued because of adverse events in 5% of patients. Extrapyramidal symptoms as adverse events were reported by 25% of the patients. Severity of extrapyramidal symptoms (according to ESRS scores) was low at baseline and decreased in each of the groups during the 12 months. The other most common adverse events were anxiety in 24%, insomnia in 21%, psychosis in 17%, and depression in 14% of the patients. Little pain was associated with the injections. Severity of symptoms of schizophrenia was improved in each group, with significant reductions in PANSS total scores (p <.01) and positive (p <.01) and negative (p <.001) factor scores. CONCLUSION: In terms of both safety and efficacy, symptomatically stable patients with schizophrenia benefit from being switched to long-acting injectable risperidone.

Different corticostriatal patterns of L-DOPA utilization in patients with untreated schizophrenia and patients treated with classical antipsychotics or clozapine.

Positron emission tomography (PET) has been shown to be of great importance in elucidating the mechanism of action of antipsychotic drugs. In psychotic patients L-[11C]DOPA PET has been used to demonstrate some differences in dopaminergic activity compared with that in healthy volunteers. Ten healthy volunteers were investigated with PET and L-[11C]DOPA. Ten drug-free patients with psychosis, nine stable schizophrenics treated with clozapine, and nine stable patients treated with classical antipsychotics were also investigated with L-[11C]DOPA. Principal-component analysis was employed for the analysis of L-[11C]DOPA Ki values across a number of corticostriatal brain regions. These data revealed a significant three-component model with clear-cut separation between healthy controls and patients with unmedicated schizophrenia. Stable optimal treatment with either classical neuroleptics or clozapine partially, albeit differentially, reversed the aberrant patterns seen in drug-free schizophrenia. It can thus be concluded that schizophrenia is associated with abnormal patterns of L-[11C]DOPA utilization in corticostriatal systems. Treatment with clozapine or classical neuroleptics induces partial, albeit differential, normalization of the abnormal patterns seen in untreated schizophrenia.