統合失調症の新しい治療概念における新規抗精神病薬ルラシドンの役割

13301甲第3975号博士（薬学）金沢大学博士論文本文Ful

統合失調症の新しい治療概念における新規抗精神病薬ルラシドンの役割

13301甲第3975号博士（薬学）金沢大学博士論文要旨Abstrac

Effect of lurasidone dose on cognition in patients with schizophrenia: Post-hoc analysis of a long-term, double-blind continuation study

We previously reported that treatment with 160mg/d of lurasidone improved cognitive performance in a manner superior to placebo, quetiapine XR 600mg/d, and lurasidone 80mg/d, based on a 6-week randomized trial of patients with an acute exacerbation of schizophrenia. The objective of this post-hoc analysis was to explore the cognitive and functional performance of patients whose final doses of lurasidone were 40/80mg/d, 120mg/d, and 160mg/d compared to quetiapine XR 200-800mg/d (QXR) during a 6-month, double-blind continuation study that followed a short-term trial. Subjects who received final doses of lurasidone 120mg/d (n=77) and 160mg/d (n=49) showed significantly greater improvement in overall cognitive performance compared to QXR (n=85) at week 32 (month 6 of the extension study), while those on last doses of 40/80mg/d (n=25) showed a trend towards significance at week 32. Mean changes in neurocognitive composite z-score from pre-treatment baseline were significant for the 3 lurasidone final dose groups at both weeks 19 and 32, with composite change scores of z=1.53, z=1.43, and z=1.34 for the lurasidone 40/80mg/d, 120mg/d, and 160mg/d, respectively, at week 32. In contrast, the composite change score was not statistically significant in the overall quetiapine group (z=0.46), with none of the individual quetiapine doses showing any significant improvement. Functional capacity scores improved in all treatment groups. Our findings indicate improved cognitive performance in patients treated with each of the flexible doses of lurasidone 40–160mg/d, compared to quetiapine XR 200–800mg/d. All doses of lurasidone were superior to all doses of quetiapine for cognitive performance

Tremendous Enhancement of Torque Density in HTS Induction/Synchronous Machine for Transportation Equipments

We succeeded in tremendous enhancement of torque density as well as power density in High Temperature Superconducting Induction/Synchronous Machine (HTS-ISM) for next generation transportation equipments. First, we fabricated and tested the 20 kW-class prototype as the validation of our design concept (1st generation). And then, the 70% reduction of the motor's volume is challenged with the same power (2nd generation). We successfully realized the tremendous enhancement of the torque density, and further the overload tolerance was also realized at the steady state

Performance and interview-based assessments of cognitive change in a randomized, double-blind comparison of lurasidone vs. ziprasidone

Improving cognitive functioning in people with schizophrenia is a major treatment goal. In addition, interview-based measures have been developed to supplement performance-based assessments. However, few data are available regarding whether interview-based measures are sensitive to treatment-related changes. Adult outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomized to 21days of double-blind treatment with lurasidone 120mg once daily (N=150) or ziprasidone 80mg BID (N=151). A similar proportion of patients completed the study on lurasidone (67.5%) and ziprasidone (69.3%). Study participants were assessed with the majority of the tests from the MATRICS Consensus Cognitive Battery (MCCB) and an interview-based assessment of cognitive functioning, the Schizophrenia Cognition Rating Scale (SCoRS). SCoRS ratings were based on the interviewer's best judgment, after interviews with the patient and a caregiver when available. The study was conducted from April 2006 to January 2007. There were no between-group treatment differences in performance on the MCCB or the SCoRS ratings. Lurasidone patients demonstrated significant within group-improvement from baseline on the MCCB composite score (p=0.026) and on the SCoRS (p<0.001), but ziprasidone patients did not improve on either the MCCB composite (p=0.254) or the SCoRS (p=0.185). At endpoint there was a statistical trend (p=0.058) for lurasidone to demonstrate greater improvement from baseline in SCoRS ratings. Improvements in interview-based aspects of cognition were not related to MCCB test changes, and had minimal correlations with changes in symptoms. These data suggest that interview-based cognitive measures such as the SCoRS may be sensitive to changes after 3weeks of treatment in patients with schizophrenia. Lurasidone is being assessed further in ongoing clinical trials with additional outcome measures