A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone.
ABSTRACT Long-acting injectable risperidone represents the first clinically available depot atypical antipsychotic. The present study used positron emission tomography (PET) to evaluate its dopamine D(2) binding profile at doses of 25, 50, or 75 mg administered every 2 weeks.
After achieving stabilization with one of the doses, nine patients with a diagnosis of schizophrenia or schizoaffective disorder underwent [(11)C]raclopride PET to measure D(2) occupancy. Participants were scanned twice during the 2-week injection interval: within 3 days after injection (postinjection) and within 5 days before the next injection (preinjection). At the same time, plasma was collected for measurements of risperidone plus 9-hydroxyrisperidone.
Mean post- and preinjection D(2) occupancy levels for the 25-, 50-, and 75-mg doses were 71.0% and 54.0%, 74.4% and 65.4%, and 81.5% and 75.0%, respectively. There was a significant correlation between dose and plasma concentrations of risperidone plus 9-hydroxyrisperidone, and the estimated plasma concentration associated with 50% D(2) occupancy (ED(50)) was 11.06 ng/ml. Prolactin levels were not correlated with drug levels or D(2) occupancy.
All three doses of injectable risperidone showed peak D(2) occupancy levels above the 65% threshold associated with optimal clinical response; the 75-mg dose approximated the 80% threshold linked to increased risk of extrapyramidal symptoms. Doses of 25 or 50 mg should provide therapeutic efficacy while minimizing the risk of extrapyramidal symptoms.
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ABSTRACT: Several genetic factors have been identified that, in combination with clinical and environmental factors, contribute to the variability in response to treatment with antipsychotic drugs. Functional polymorphisms in genes coding for cytochrome-P450 (CYP) enzymes, responsible for the metabolism of over 85 % of drugs, have been associated with the development of drug-induced side-effects, and functional polymorphisms in dopamine and serotonin genes may be associated with adverse reactions and treatment efficacy. Recent estimations have suggested that selecting the drug and clinical dose according to the patient’s genetic profile may result in a significant improvement of treatment efficacy (10–15 %) and safety (15–20 %). This information has prompted the development of commercial kits to facilitate the clinical application of pharmacogenetic information. However, prospective studies confirming the clinical and economical benefits of these tests are required before their widespread implementation in clinical practice.Current Genetic Medicine Reports. 03/2013; 1(1).
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ABSTRACT: Objective Dopamine supersensitivity psychosis (DSP) is considered to be one cause of treatment-resistant schizophrenia (TRS). The authors investigated the efficacy of risperidone long-acting injections (RLAI) in patients with TRS and DSP. Method This is a multicenter, prospective, 12-month follow-up, observational study that included unstable and severe TRS patients with and without DSP. 115 patients with TRS were recruited and divided into two groups according to the presence or absence of DSP which was judged on the basis of the clinical courses and neurological examinations. RLAI was administered adjunctively once every 2 weeks along with oral antipsychotics. We observed changes in scores for the Brief Psychiatric Rating Scales (BPRS), Clinical Global Impression—Severity of Illness (CGI-S), Global Assessment of Functioning Scale (GAF), and Extrapyramidal Symptom Rating Scale (ESRS) during the study. Of the assessed 94 patients, 61 and 33 were categorized into the DSP and NonDSP groups, respectively. Results While baseline BPRS total scores, CGI-S scores and GAF scores did not differ, the ESRS score was significantly higher in the DSP group compared with the NonDSP group. Treatment significantly reduced BPRS total scores and CGI-S scores, and increased GAF scores in both groups, but the magnitudes of change were significantly greater in the DSP group relative to the NonDSP group. ESRS scores were also reduced in the DSP group. Responder rates (≥ 20% reduction in BPRS total score) were 62.3% in the DSP group and 21.2% in the NonDSP group. Conclusions It is suggested that DSP contributes to the etiology of TRS. Atypical antipsychotic drugs in long-acting forms, such as RLAI, can provide beneficial effects for patients with DSP. Clinical trials registration: UMIN (UMIN000008487).Schizophrenia Research 05/2014; · 4.43 Impact Factor
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ABSTRACT: BACKGROUND: The second generation antipsychotics represent the great achievement in the treatment of schizophrenia of the last decades. However in the last years some new antipsychotics were synthesized and such new compounds may represent great perspectives for the field of the treatment of schizophrenia. Some of these compounds are in use while others are still on evaluation through clinical trials. OBJECTIVE: Summarize the current knowledge of new antipsychotics. METHODS: PubMed search as well literature provided by the manufactures. RESULTS AND CONCLUSIONS: We present the main pharmacological characteristics as well as profiles of efficacy, security and tolerability of the following compounds: Asenapine, ACP-103, Bifeprunox, Paliperidone, Long Acting Injectable Risperidone and Sertindole.Revista de Psiquiatria Clínica 12/2006; 34:193-197. · 0.89 Impact Factor