ACUTE MANIA--HALOPERIDOL DOSE AND LORAZEPAM AUGMENTATION

急性躁狂症——氟哌啶醇剂量和劳拉西泮增量

• 批准号: 3429478
• 负责人: James C Chou
• 金额: $ 7.24万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3429478
• 关键词: adolescence (12-20); bipolar depression manic phase; blood chemistry; clinical trials; combination chemotherapy; dosage; drug administration rate /duration; drug adverse effect; drug detection; haloperidol; human middle age (35-64); human therapy evaluation; lithium; lorazepam; mental disorder chemotherapy; neuropsychological tests; young adult human (21-34)

Manic psychosis often requires neuroleptic (NL) treatment, and the NL doses used in mania are often high. A global objective of our work is to describe the lowest effective haloperidol (HAL) dose for acute mania. Lorazepam (LZP) augmentation may allow use of lower NL doses, so we will study the effects of adding LZP to two different doses of HAL> Also, we will study effects of adding lithium (Li) to HAL so that results about HAL dose will be generalizable to standard Li-NL treatment. Enough acutely psychotic bipolar manic subjects to obtain 60 completers will receive either HAL 25md/d (usual dose) or HAL 5mg/d (low dose) under double-blind conditions for 3 weeks. In addition to HAL, subjects will receive either placebo, LZP 4mg/d, or standard Li treatment, also under double blind conditions. HAL, Li and LZP blood levels will be measured weekly. Clinical ratings will include the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression, and Manic-State Rating Scale. Side effects will be rated with the Neurologic Rating Scale, Treatment Emergent Symptoms Scale, and an akathisia scale. We will test the hypotheses that: 1) Clinical improvement (on BPRS) is related to HAL dose (and blood level), i.e. HAL 25mg/d produces more improvement that HAL 5mg/d.; 2) HAL side effects are related to HAL dose (and blood level), i.e. HAL25mg/d produces more HAL side effects than HAL 5mg/d. 3) LZP increases clinical improvement, while Li does not. 4) LZP (or Li) increases HAL blood levels. 5) In LZP-treated patients LZP blood levels are related to clinical response, and LZP has both pharmacokinetic and pharmacodynamic interactions with HAL. 6) Li increases HAL side effects. As a secondary hypothesis, if HAL 25mg/d produces greater clinical improvement than HAL 5mg/d then, 7) Any advantage of HAL 25mg/d (alone) over HAL 5mg/d (alone) is made up by LZP augmentation.

躁狂精神病通常需要神经肌饮质（NL）治疗，而NL剂量 在躁狂症中使用通常很高。 我们工作的全球目标是 描述急性躁狂症的最低有效氟哌啶醇（HAL）剂量。 Lorazepam（LZP）增强可能允许使用较低的NL剂量，因此我们将 研究将LZP添加到两种不同剂量的HAL>的效果。 将研究将锂（Li）添加到HAL的效果，从而导致HAL 剂量将可以推广到标准LI-NL治疗。 足够的急性精神病性躁郁症受试者获得60个完成者 将接受HAL 25MD/D（通常剂量）或HAL 5mg/d（低剂量） 双盲条件3周。 除了HAL，受试者还将 接受安慰剂，LZP 4mg/d或标准LI治疗 双盲条件。 HAL，LI和LZP血液水平将被测量 每周。 临床评级将包括简短的精神病量表 （BPR），临床全球印象和躁狂状态评级量表。 边 效果将通过神经系统评级量表进行评分，治疗出现 症状尺度和akathisia量表。 我们将测试以下假设： 1）临床改善（BPRS）与HAL剂量（和血液水平）有关， 即HAL 25mg/d可产生比HAL 5mg/d的更多改进。 2）HAL副作用与HAL剂量（和血液水平）有关，即 HAL25mg/d比HAL 5mg/d产生更多的HAL副作用。 3）LZP增加了临床改善，而LI却没有。 4）LZP（或LI）增加了HAL血液水平。 5）在LZP治疗的患者中，LZP血液水平与临床有关 反应，LZP具有药代动力学和药效相互作用 与HAL。 6）LI增加了HAL副作用。 作为次要假设，如果HAL 25mg/d会产生更大的临床 比HAL 5mg/d的改进，然后 7）HAL 25mg/d（单独）比HAL 5mg/d（单独）的任何优势由 LZP增强。