Chia-Hao Ma, Hung-Yu Chan, Ming H Hsieh, Chen-Chung Liu, Chih-Min Liu, Hai-Gwo Hwu, Ching-Hua Kuo, Wei J Chen, Tzung-Jeng Hwang
{"title":"通过一项随机对照研究确定精神分裂症患者从其他抗精神病药物切换到阿立哌唑的多巴胺超敏感性。","authors":"Chia-Hao Ma, Hung-Yu Chan, Ming H Hsieh, Chen-Chung Liu, Chih-Min Liu, Hai-Gwo Hwu, Ching-Hua Kuo, Wei J Chen, Tzung-Jeng Hwang","doi":"10.1177/20451253211064396","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Aripiprazole has been reported to worsen psychotic symptoms when switching from other antipsychotics, possibly due to dopamine supersensitivity psychosis.</p><p><strong>Objective: </strong>This study aimed to explore the predictors and possible underlying mechanisms of aripiprazole-related psychotic exacerbation.</p><p><strong>Methods: </strong>We conducted an 8-week, open-label, randomized controlled study from October 2007 to September 2009, assigning patients with a primary diagnosis of schizophrenia or schizoaffective disorder to switch from other antipsychotics to aripiprazole with 2-week dual administration, and then to taper off the original agents in fast (n = 38, within 1 week) or slow (n = 41, within 4 weeks) strategies. Positive and Negative Syndrome Scale (PANSS) was examined at day 0, 7, 14, 28, 56. Aripiprazole-related exacerbation (ARE) was defined positive as a 2-point increase in delusion/hallucination dimension score within 28 days compared with baseline. Baseline demographic, clinical and intervention-related variables were compared between the ARE+ and ARE- groups.</p><p><strong>Results: </strong>Of the 79 randomized patients, 21 fulfilled the criteria of ARE+ , and 46 were classified as ARE-. Fourteen patients in the ARE+ group had worsening psychotic symptoms in the first and second weeks. Compared with the ARE- group, the ARE+ group had a higher baseline chlorpromazine equivalent dose (405.8 ± 225.8 mg vs 268.1 ± 165.4 mg, <i>p</i> = 0.007) and was associated with prescription of first-generation antipsychotics (<i>p</i> = 0.038).</p><p><strong>Conclusions: </strong>A higher dose of original antipsychotics and prescription of first-generation antipsychotics may be associated with a higher risk of ARE. The underlying mechanism might be covert dopamine supersensitivity psychosis. These findings may help to identify high-risk patients and guide appropriate treatment strategies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, identifier: NCT00545467.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b6/2f/10.1177_20451253211064396.PMC8801645.pdf","citationCount":"0","resultStr":"{\"title\":\"Identifying dopamine supersensitivity through a randomized controlled study of switching to aripiprazole from other antipsychotic agents in patients with schizophrenia.\",\"authors\":\"Chia-Hao Ma, Hung-Yu Chan, Ming H Hsieh, Chen-Chung Liu, Chih-Min Liu, Hai-Gwo Hwu, Ching-Hua Kuo, Wei J Chen, Tzung-Jeng Hwang\",\"doi\":\"10.1177/20451253211064396\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Aripiprazole has been reported to worsen psychotic symptoms when switching from other antipsychotics, possibly due to dopamine supersensitivity psychosis.</p><p><strong>Objective: </strong>This study aimed to explore the predictors and possible underlying mechanisms of aripiprazole-related psychotic exacerbation.</p><p><strong>Methods: </strong>We conducted an 8-week, open-label, randomized controlled study from October 2007 to September 2009, assigning patients with a primary diagnosis of schizophrenia or schizoaffective disorder to switch from other antipsychotics to aripiprazole with 2-week dual administration, and then to taper off the original agents in fast (n = 38, within 1 week) or slow (n = 41, within 4 weeks) strategies. Positive and Negative Syndrome Scale (PANSS) was examined at day 0, 7, 14, 28, 56. Aripiprazole-related exacerbation (ARE) was defined positive as a 2-point increase in delusion/hallucination dimension score within 28 days compared with baseline. Baseline demographic, clinical and intervention-related variables were compared between the ARE+ and ARE- groups.</p><p><strong>Results: </strong>Of the 79 randomized patients, 21 fulfilled the criteria of ARE+ , and 46 were classified as ARE-. Fourteen patients in the ARE+ group had worsening psychotic symptoms in the first and second weeks. Compared with the ARE- group, the ARE+ group had a higher baseline chlorpromazine equivalent dose (405.8 ± 225.8 mg vs 268.1 ± 165.4 mg, <i>p</i> = 0.007) and was associated with prescription of first-generation antipsychotics (<i>p</i> = 0.038).</p><p><strong>Conclusions: </strong>A higher dose of original antipsychotics and prescription of first-generation antipsychotics may be associated with a higher risk of ARE. The underlying mechanism might be covert dopamine supersensitivity psychosis. These findings may help to identify high-risk patients and guide appropriate treatment strategies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, identifier: NCT00545467.</p>\",\"PeriodicalId\":23127,\"journal\":{\"name\":\"Therapeutic Advances in Psychopharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2022-01-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b6/2f/10.1177_20451253211064396.PMC8801645.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/20451253211064396\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/20451253211064396","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
背景:有报道称阿立哌唑在从其他抗精神病药物转用后会加重精神病症状,可能是由于多巴胺超敏感性精神病。目的:探讨阿立哌唑相关精神病加重的预测因素及可能的潜在机制。方法:从2007年10月至2009年9月,我们进行了一项为期8周的开放标签随机对照研究,将初步诊断为精神分裂症或分裂情感性障碍的患者从其他抗精神病药物切换到阿立哌唑,为期2周的双重给药,然后以快速(n = 38,在1周内)或缓慢(n = 41,在4周内)的策略逐渐减少原药物。分别于第0、7、14、28、56天检测阳性和阴性综合征量表(PANSS)。阿立哌唑相关恶化(ARE)被定义为28天内妄想/幻觉维度评分较基线增加2分。比较ARE+组和ARE-组的基线人口学、临床和干预相关变量。结果:79例随机患者中,21例符合ARE+标准,46例为ARE-。ARE+组14例患者在第1周和第2周出现精神病症状加重。与ARE-组相比,ARE+组氯丙嗪基线等效剂量更高(405.8±225.8 mg vs 268.1±165.4 mg, p = 0.007),且与第一代抗精神病药物处方相关(p = 0.038)。结论:较高的原始抗精神病药物剂量和第一代抗精神病药物处方可能与较高的ARE风险相关。潜在的机制可能是隐性多巴胺超敏性精神病。这些发现可能有助于识别高危患者并指导适当的治疗策略。试验注册:ClinicalTrials.gov,标识符:NCT00545467。
Identifying dopamine supersensitivity through a randomized controlled study of switching to aripiprazole from other antipsychotic agents in patients with schizophrenia.
Background: Aripiprazole has been reported to worsen psychotic symptoms when switching from other antipsychotics, possibly due to dopamine supersensitivity psychosis.
Objective: This study aimed to explore the predictors and possible underlying mechanisms of aripiprazole-related psychotic exacerbation.
Methods: We conducted an 8-week, open-label, randomized controlled study from October 2007 to September 2009, assigning patients with a primary diagnosis of schizophrenia or schizoaffective disorder to switch from other antipsychotics to aripiprazole with 2-week dual administration, and then to taper off the original agents in fast (n = 38, within 1 week) or slow (n = 41, within 4 weeks) strategies. Positive and Negative Syndrome Scale (PANSS) was examined at day 0, 7, 14, 28, 56. Aripiprazole-related exacerbation (ARE) was defined positive as a 2-point increase in delusion/hallucination dimension score within 28 days compared with baseline. Baseline demographic, clinical and intervention-related variables were compared between the ARE+ and ARE- groups.
Results: Of the 79 randomized patients, 21 fulfilled the criteria of ARE+ , and 46 were classified as ARE-. Fourteen patients in the ARE+ group had worsening psychotic symptoms in the first and second weeks. Compared with the ARE- group, the ARE+ group had a higher baseline chlorpromazine equivalent dose (405.8 ± 225.8 mg vs 268.1 ± 165.4 mg, p = 0.007) and was associated with prescription of first-generation antipsychotics (p = 0.038).
Conclusions: A higher dose of original antipsychotics and prescription of first-generation antipsychotics may be associated with a higher risk of ARE. The underlying mechanism might be covert dopamine supersensitivity psychosis. These findings may help to identify high-risk patients and guide appropriate treatment strategies.
期刊介绍:
Therapeutic Advances in Psychopharmacology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of psychopharmacology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in psychopharmacology, providing a forum in print and online for publishing the highest quality articles in this area.