D2 receptor occupancy following lurasidone treatment in patients with schizophrenia or schizoaffective disorder. (30th September 2013)

• Record Type: Journal Article
• Authors: Potkin, Steven G.; Keator, David B.; Kesler-West, Marilyn L.; Nguyen, Dana D.; van Erp, Theo. G. M.; Mukherjee, Jogeshwar; Shah, Nikunj; Preda, Adrian
• Is Part Of: CNS spectrums. Volume 19:Number 2(2014:Apr.)
• Page Start: 176
• Page End: 181
• Publication Date: 2013-09-30
• Subjects: Neuropsychiatry -- Periodicals; Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1017/S109285291300059X
• Languages: English
• ISSNs: 1092-8529

Abstract

<abstract abstract-type="normal"> <title> <x content-type="archive" xml:space="preserve">Abstract</x> </title> <sec id="abs1" sec-type="general"> <title>Objective/Introduction</title> <p>Lurasidone is an atypical antipsychotic medication approved for the treatment of schizophrenia over a dose range of 40–160 mg/day. This study examined D<sub>2</sub> receptor occupancy and its association with clinical improvement and side effects in patients with schizophrenia or schizoaffective disorder following repeated doses of 80, 120, or 160 mg/day of lurasidone.</p> </sec> <sec id="abs2" sec-type="methods"> <title>Methods</title> <p>Twenty-five patients with <italic>The Diagnostic and Statistical Manual of Mental Disorders</italic>, 4th ed. (DSM-IV) diagnoses of schizophrenia or schizoaffective disorder were washed out of their antipsychotic medications (5 half-lives) and randomly assigned to 80, 120, or 160 mg/day of lurasidone. Subjects were imaged with 18F-fallypride at baseline and at steady-state lurasidone treatment to determine D<sub>2</sub> receptor occupancy.</p> </sec> <sec id="abs3" sec-type="results"> <title>Results</title> <p>Blood lurasidone concentration (plus major metabolite), but not dose, significantly correlated with D<sub>2</sub> receptor occupancy. D<sub>2</sub> receptor occupancy in several subcortical structures is associated with positive but not negative symptom improvement or the presence of movement symptoms.</p> </sec> <sec id="abs4" sec-type="discussion"> <title>Discussion</title> <p>Blood concentrations greater than 70 ng/mL may be required to achieve a 65% occupancy level in subcortical areas. Intersubject blood concentrations at fixed dose were highly variable and may account for the lack of dose correlations.</p> </sec> <sec id="abs5" sec-type="conclusion"> <title>Conclusions</title> <p>Positron emission tomography (PET) occupancy data suggest that greater than 65% occupancy can be achieved across the dose range of 80–160 mg/day and that some patients require higher doses to achieve antipsychotic efficacy; this finding supports prior randomized clinical trial results.</p> </sec> </abstract>