Uchida Hiroyuki, Mamo David C, Kapur Shitij, Labelle Alain, Shammi Chekkera, Mannaert Erik J L, Mann Steve W, Remington Gary
Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
J Clin Psychiatry. 2008 Aug;69(8):1281-6. doi: 10.4088/jcp.v69n0811.
Long-acting risperidone administered intramuscularly biweekly is approved for the management of schizophrenia. However, dosing of long-acting antipsychotics is frequently extended in clinical practice, and a recent clinical trial has lent support to monthly dosing of long-acting risperidone. The objective of this positron emission tomography (PET) study was to examine the striatal dopamine D(2) binding of long-acting risperidone administered intramuscularly once a month.
Following at least 3 maintenance monthly injections of 50 mg long-acting risper-idone, 7 patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder under-went PET using [(11)C]raclopride to measure D(2) binding potential within 4 days of the next scheduled injection. Data were collected from May to October 2003. This PET study was part of a larger 52-week clinical study wherein individuals received long-acting risperidone once monthly over a 1-year interval. One-year follow-up data were obtained from the 52-week parent investigation.
The mean +/- SD D(2) receptor occupancy was 56% +/- 24% (range, 29%-82%). Of note, there were 4 subjects with less than 60% D(2) occupancy, none of whom relapsed over the course of the 1-year follow-up. The mean +/- SD total plasma level of risperidone plus 9-hydroxyrisperidone was 16.6 +/- 12.3 ng/mL (range, 5.7-40.8).
As with plasma levels, there was considerable variability in D(2) occupancy levels for individuals receiving long-acting risperidone. This work suggests a possibility that sustained D(2) occupancy at or above the accepted threshold with acute clinical response may not be necessary to maintain response, a hypothesis with important clinical implications as we consider antipsychotic dosing and future antipsychotic development.
clinicaltrials.gov Identifier: NCT00236353.
每两周一次肌肉注射长效利培酮被批准用于治疗精神分裂症。然而，在临床实践中长效抗精神病药物的给药间隔常常延长，并且最近一项临床试验支持了长效利培酮每月给药一次。这项正电子发射断层扫描（PET）研究的目的是检查每月一次肌肉注射长效利培酮后的纹状体多巴胺D(2)受体结合情况。
在至少3次每月50mg长效利培酮维持注射后，7例诊断为精神分裂症或分裂情感性障碍的DSM-IV患者在下一次预定注射的4天内接受使用[(11)C]雷氯必利的PET检查以测量D(2)受体结合潜能。数据收集于2003年5月至10月。这项PET研究是一项更大规模的52周临床研究的一部分，在该研究中个体在1年的时间间隔内每月接受一次长效利培酮治疗。1年的随访数据来自于52周的主要研究。
D(2)受体占有率的均值±标准差为56%±24%（范围为29%-82%）。值得注意的是，有4例受试者的D(2)占有率低于60%，在1年的随访过程中他们均未复发。利培酮加9-羟基利培酮的血浆总水平均值±标准差为16.6±12.3 ng/mL（范围为5.7-40.8）。
与血浆水平一样，接受长效利培酮治疗的个体D(2)占有率水平存在相当大的变异性。这项研究表明，维持临床反应可能并不一定需要将D(2)占有率持续保持在或高于公认阈值并伴有急性临床反应，在我们考虑抗精神病药物给药和未来抗精神病药物研发时，这一假设具有重要的临床意义。
clinicaltrials.gov标识符：NCT00236353。
