The pharmacokinetics and tolerability of long-acting risperidone (Risperdal Consta) were evaluated in a multicenter, prospective, open-label, 15-week study of 86 patients with schizophrenia. Subjects stabilized on 2, 4 or 6 mg of oral risperidone once daily for at least 4 weeks were assigned to receive i.m. injections of 25, 50 or 75 mg of risperidone, respectively, every 2 weeks for 10 weeks. The 90% confidence intervals for the i.m./oral ratios of the mean steady-state plasma-AUC, corrected for dosing interval, and of the average plasma concentration of the active moiety (risperidone plus 9-hydroxyrisperidone) were within the range of 80-125%, indicating bioequivalence of the i.m. and oral formulations. However, mean steady-state peak concentrations of the active moiety were 25-32% lower with i.m. than oral dosing (P < 0.05) and fluctuations in plasma active-moiety levels were 32-42% lower with the i.m. than oral regimen. Symptoms of schizophrenia continued to improve after switching from oral to i.m. dosing. Long-acting risperidone was well tolerated locally and systematically. Although overall bioequivalence of the two formulations was established, the differences in pharmacokinetic profiles between the two formulations indicate potential benefits for long-acting risperidone.

Bipolar disorder is a multidimensional illness typified by fluctuating periods of depression and mania, cognitive dysfunction, abnormal circadian rhythms, and multiple comorbid psychiatric and general medical conditions. Indefinite pharmacological treatment is often required, yet the modest effects of available treatments and frequent difficulties with tolerability and adherence present complex challenges to patients. Long-acting injectable medications offer a therapeutic alternative to oral mood stabilizers and may help facilitate long-term treatment adherence. This article will provide a succinct review of the latest data on the use of long-acting injectable risperidone (LAR) during the maintenance phase treatment of bipolar disorder. The specific role of LAR in comparison to other atypical antipsychotics, and the limitations of available studies will be discussed from the perspectives of efficacy, tolerability, and sequential positioning in treatment guidelines.

Modern atypical antipsychotics have advantages over older neuroleptics. We hypothesize that their utility may be further enhanced by sustained drug delivery without daily oral self-dosing. This report examines the effects of a year of treatment with long-acting risperidone for chronically psychotic patients previously stabilized with oral risperidone. This open trial of long-acting risperidone involved 336 patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder judged clinically stable on a consistent daily oral dose of risperidone for > or =4 wk. Based on oral doses, subjects were assigned clinically to bi-weekly intramuscular injections of 25-75 mg of long-acting risperidone for up to 50 wk. Clinical assessments at regular intervals included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale, adverse event reports, and the Extrapyramidal Symptom Rating Scale (ESRS). PANSS total scores improved overall from a moderate baseline score of 64.5+/-17.7 to 58.8+/-19.9 at end-point (p<0.001), by> or =20% in 50% of patients, with greatest improvement in negative symptoms. Prevalence of favourable CGI - Severity ratings increased by 2.4-fold (p<0.0001). Ratings of extrapyramidal symptoms also improved [e.g. physician-rated parkinsonism scores decreased by 20% (p<0.0001)]. Tissue reactions and other adverse effects of repeated intramuscular injections were rare and mild. Psychotic patients considered stable but symptomatic with oral risperidone treatment showed further improvements in symptom ratings and extrapyramidal dysfunction during a year of bi-weekly injections of long-acting risperidone.