Striatal Dopamine D2 Receptor Occupancy Induced by Daily Application of Blonanserin Transdermal Patches: Phase II Study in Japanese Patients With Schizophrenia

Background: Transdermal antipsychotic patch formulations offer potential benefits, including improved adherence. This study investigated the striatal dopamine D-2 receptor occupancy with daily blonanserin transdermal patch application. Methods: This open-label, phase II study enrolled 18 Japanese outpatients (20 to <65 years) with schizophrenia (DSM-IV-TR criteria; total Positive and Negative Syndrome Scale score <120 at screening) treated with blonanserin 8-mg or 16-mg tablets. Patients continued tablets for 2-4 weeks at their current dose and were then assigned to once-daily blonanserin patches (10/20/40/60/80 mg daily) for 2-4 weeks based on the oral dose. [C-11]raclopride positron emission tomography scanning determined blonanserin striatal dopamine D-2 receptor occupancy (primary endpoint). Secondary endpoints included assessment of receptor occupancy by dose, changes in Positive and Negative Syndrome Scale and Clinical Global ImpressionsSeverity of Illness-Severity scores, patient attitudes towards adherence, and patch adhesiveness. Results: Of 18 patients who started the blonanserin tablet treatment period, 14 patients completed treatment. Mean D-2 receptor occupancy for blonanserin tablets 8 mg/d (59.2%, n =5) and 16 mg/d (66.3%, n =9) was within the values for blonanserin patches: 10 mg/d (33.3%, n =3), 20 mg/d (29.9%, n =2), 40 mg/d (61.2%, n =3), 60 mg/d (59.0%, n =3), and 80 mg/d (69.9%, n=3). Occupancy generally increased with increasing blonanserin dose for both formulations with the half maximal receptor occupancy for tablets and patches associated with doses of 6.9 mg/d and 31.9 mg/d, respectively. Diurnal variability in occupancy was lower during transdermal patch treatment than during tablet treatment. Blonanserin transdermal patches were well tolerated with no major safety concerns. Conclusions: Blonanserin patches (40/80 mg/d) have lower diurnal variability in occupancy than blonanserin tablets (8/16 mg/d), and patches at doses of 40 mg/d and 80 mg/d appear to be a suitable alternative for blonanserin tablets at doses of 8 mg/d and 16 mg/d, respectively. Blonanserin patches represent a potential new treatment option for patients with schizophrenia.