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Factors associated with successful antipsychotic dose reduction in schizophrenia: a systematic review of prospective clinical trials and meta-analysis of randomized controlled trials.
Neuropsychopharmacology ( IF 6.6 ) Pub Date : 2019-11-26 , DOI: 10.1038/s41386-019-0573-7
Hideaki Tani 1, 2 , Shotaro Takasu 1, 3 , Hiroyuki Uchida 1, 4 , Takefumi Suzuki 5 , Masaru Mimura 1 , Hiroyoshi Takeuchi 1, 6
Affiliation  

This systematic review and meta-analysis examined predictors of successful antipsychotic dose reduction in schizophrenia. Prospective clinical trials and randomized controlled trials (RCTs) investigating antipsychotic dose reduction in schizophrenia were selected for systematic review and meta-analysis, respectively. In total, 37 trials were identified. Only 8 studies focused on second-generation antipsychotics (SGAs); no studies investigated long-acting injectable SGAs. Of 24 studies evaluating relapse or symptom changes, 20 (83.3%) met the criteria for successful dose reduction. Factors associated with successful dose reduction were study duration < 1 year, age > 40 years, duration of illness > 10 years, and post-reduction chlorpromazine equivalent (CPZE) dose > 200 mg/day. Clinical deterioration was mostly re-stabilized by increasing the dose to the baseline level (N = 7/8, 87.5%). A meta-analysis of 18 RCTs revealed that relapse rate was significantly higher in the reduction group than the maintenance group (risk ratio [RR] = 1.96; 95% confidence interval [CI], 1.23-3.12), whereas neurocognition was significantly improved (standardized mean difference = 0.69; 95% CI, 0.25-1.12). A subgroup analysis indicated that only a post-reduction CPZE dose ≤ 200 mg/day was associated with an increased risk of relapse (RR = 2.79; 95% CI, 1.29-6.03). Thus, when reducing antipsychotic doses, clinicians should consider the long-term risk of relapse in younger patients with a relatively short illness duration and keep the final doses higher than CPZE 200 mg/day. Further studies, particularly those involving SGAs, are warranted to determine the optimal strategies for successful antipsychotic dose reduction in schizophrenia.

中文翻译:

与成功减少精神分裂症抗精神病药剂量相关的因素:前瞻性临床试验的系统评价和随机对照试验的荟萃分析。

这项系统评价和荟萃分析检查了精神分裂症成功减少抗精神病药剂量的预测因素。分别选择研究精神分裂症中抗精神病药物剂量减少的前瞻性临床试验和随机对照试验 (RCT) 进行系统评价和荟萃分析。总共确定了 37 项试验。只有 8 项研究侧重于第二代抗精神病药 (SGA);没有研究调查长效可注射 SGA。在评估复发或症状变化的 24 项研究中,20 项 (83.3%) 符合成功减少剂量的标准。与成功减少剂量相关的因素是研究持续时间 < 1 年、年龄 > 40 岁、病程 > 10 年和减少后氯丙嗪等效剂量 (CPZE) 剂量 > 200 毫克/天。通过将剂量增加到基线水平,临床恶化大多重新稳定(N = 7/8,87.5%)。对 18 项 RCT 的荟萃分析显示,减量组的复发率显着高于维持组(风险比 [RR] = 1.96;95% 置信区间 [CI],1.23-3.12),而神经认知显着改善(标准化平均差 = 0.69;95% CI,0.25-1.12)。亚组分析表明,只有减量后 CPZE 剂量≤ 200 mg/天与复发风险增加相关(RR = 2.79;95% CI,1.29-6.03)。因此,在减少抗精神病药剂量时,临床医生应考虑年轻患者病程相对较短的长期复发风险,并保持最终剂量高于 CPZE 200 mg/天。进一步的研究,特别是那些涉及 SGA 的研究,
更新日期:2019-11-27
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