Uptown Research Institute, LLC, Chicago, Illinois, USA.
Dr Weiden is now an employee of Alkermes, Inc, Waltham, Massachusetts, USA.
J Clin Psychiatry. 2017 Jul;78(7):e813-e820. doi: 10.4088/JCP.16m11308.
To evaluate the effect of 1 oral and 2 distinct long-acting injectable (LAI) formulations of the same antipsychotic on times to relapse following medication discontinuation.
Data were drawn from 3 similarly designed, multicenter, double-blind, placebo-controlled, randomized-withdrawal studies of paliperidone in adults with a schizophrenia diagnosis (according to DSM-IV criteria for ≥ 1 year before screening): once-daily extended-release oral paliperidone (ORAL paliperidone), once-monthly paliperidone palmitate (PP1M), and once-every-3-months paliperidone palmitate (PP3M). In a post hoc analysis, we compared median time to relapse across the treatment-withdrawal arms of the 3 studies using final analysis datasets. Time to relapse in the withdrawal arm of each study was examined using log-rank tests and Cox proportional hazards models.
Four hundred forty-nine patients were withdrawn from 3 paliperidone formulations: 101 from ORAL paliperidone, 203 from PP1M, and 145 from PP3M. Postwithdrawal median (95% confidence interval [CI]) days to relapse were 58 days (42-114 days) for ORAL paliperidone, 172 days (134-222 days) for PP1M, and 395 days (274 days-not reached) for PP3M (P < .0001, pairwise comparisons). Relapse risk was significantly lower (P < .001) for patients who withdrew from either PP formulation relative to ORAL paliperidone and additionally for patients who withdrew from PP3M relative to PP1M.
Results demonstrate that 50% of patients who withdrew treatment from ORAL paliperidone, PP1M, or PP3M remained relapse free for approximately 2 months, 6 months, and 13 months, respectively. This may be relevant for risk mitigation strategies in schizophrenia, a condition in which interruptions in maintenance antipsychotic treatment are commonplace and unpredictable. LAI antipsychotic formulations may provide substantial delays over oral equivalents in times to relapse when patients discontinue therapy.
ClinicalTrials.gov identifiers: NCT00086320, NCT00111189, and NCT01529515.
评估同一种抗精神病药物的 1 种口服制剂和 2 种不同长效注射剂（LAI）在停药后复发时间上的效果。
数据来自 3 项设计相似、多中心、双盲、安慰剂对照、随机撤药的成人精神分裂症诊断（DSM-IV 标准≥1 年）帕利哌酮研究：每日 1 次口服缓释帕利哌酮（ORAL 帕利哌酮）、每月 1 次棕榈酸帕利哌酮（PP1M）和每 3 个月 1 次棕榈酸帕利哌酮（PP3M）。在一项事后分析中，我们使用最终分析数据集比较了 3 项研究的撤药治疗臂之间的中位复发时间。使用对数秩检验和 Cox 比例风险模型检查每个研究撤药臂的复发时间。
449 例患者退出了 3 种帕利哌酮制剂的研究：101 例来自 ORAL 帕利哌酮，203 例来自 PP1M，145 例来自 PP3M。撤药后中位（95%置信区间[CI]）复发时间分别为：ORAL 帕利哌酮 58 天（42-114 天）、PP1M 172 天（134-222 天）、PP3M 395 天（274 天-未达到）（P<0.0001，两两比较）。与 ORAL 帕利哌酮相比，退出任何一种 PP 制剂的患者（P<0.001），以及退出 PP3M 的患者（P<0.001），其复发风险显著降低。
结果表明，50%退出 ORAL 帕利哌酮、PP1M 或 PP3M 治疗的患者，分别有约 2 个月、6 个月和 13 个月的时间保持无复发状态。这对于精神分裂症的风险缓解策略可能具有重要意义，因为中断维持性抗精神病药物治疗在这种情况下很常见且不可预测。当患者停止治疗时，LAI 抗精神病药物制剂可能会比口服制剂在复发时间上产生显著的延迟。
ClinicalTrials.gov 标识符：NCT00086320、NCT00111189 和 NCT01529515。
