Aripiprazole worsens psychosis: a case report.
Aripiprazole worsens psychosis: a case report.
复制标题
阿立哌唑使精神病恶化：病例报告。
DOI：
10.4088/pcc.v08n0611e
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
N. Gupta
中科院分区：
文献类型：
--
作者：
S. Grover;P. Sharan;N. Gupta
先生：阿立哌唑是第二代抗精神病药物，具有独特的作用机制。阿立哌唑作为多巴胺和5-羟色胺受体的功能拮抗剂或功能激动剂，取决于周围环境中相关神经递质的水平，因此，它被称为多巴胺-5-羟色胺系统稳定剂。1由于阿立哌唑的部分激动剂D2受体活性，它被认为可以恶化精神疾病。
我们报告了一个阿立哌唑独特的作用机制可能导致精神病症状复发的病例。
案件报告。A女士，24岁，研究生，2000年12月出现一种潜伏性疾病，病程为5年，特征为参照、控制和迫害妄想；思想广播；以及评论和讨论型幻听。这些症状导致明显的功能障碍(全球功能评估3分=30分)。诊断为偏执型精神分裂症(ICD-10和DSM-IV)，最初用利培酮(最大剂量为6 mg/d，总疗程为24个月)、三氟拉嗪(最大剂量为25 mg/d，总疗程为15个月)、奥氮平(最大剂量为25 mg/d，共4个月)和奎硫平(最大剂量为600 mg/d，共4个月)进行治疗。
在每一种药物治疗中，A女士最初都表现出部分改善(约1分临床总体印象量表[CGI]4分)，随后在几周内恶化到以前的水平。由于她(和她的家人)继续拒绝氯氮平，她被改用氟哌啶醇(最大剂量=30毫克/天，总疗程2个月)。使用氟哌啶醇后，她的初始改善很小(1个CGI分)，所以加用阿立哌唑(最大剂量=20毫克/天，总疗程2个月)。在两种药物的联合使用下，尽管氟哌啶醇剂量增加(最大剂量=60毫克/天)，但她的症状恶化(2 CGI分)。阿立哌唑逐渐停药后，A女士的症状开始好转。
在接下来的5个月里，她在每天服用60毫克氟哌啶醇的治疗中保持了进步(大约比阿立哌唑和氟哌啶醇联合使用的水平高出3个CGI点)。据她的家人说，这是这位患者在过去5年中达到的最好状态。客观地说，她此时的阳性和阴性症状量表5阳性症候群得分为0。
阿立哌唑在高多巴胺环境中作为D2受体拮抗剂，在低多巴胺环境中作为激动剂。在指征病例中，氟哌啶醇是一种有效的D2拮抗剂，它的存在导致了低多巴胺能状态。在低多巴胺能环境中，阿立哌唑起激动剂作用，导致症状恶化。这一假说尤其适用于目前的病例，因为停用阿立哌唑可以改善精神病症状。我们的病例是少数报道这种现象的病例的补充，2，4，6，7，提示在添加阿立哌唑以增强抗精神病药物的作用时需要谨慎。
Sir: Aripiprazole is a second-generation antipsychotic medication with a unique mechanism of action. It acts as a functional antagonist or functional agonist at dopamine and serotonin receptors, depending upon the level of the relevant neurotransmitter in the immediate environment, and for this reason, it is known as a dopamine-serotonin system stabilizer.1 Due to the partial-agonist D2 receptor activity of aripiprazole, it has been suggested to worsen psychosis.2
We report a case in which the unique mechanism of action of aripiprazole probably contributed to relapse of psychotic symptoms.
Case report. Ms. A, a 24-year-old graduate student, presented in December 2000 with an insidious-onset illness of 5 years' duration characterized by delusions of reference, control, and persecution; thought broadcast; and auditory hallucinations of commenting and discussing type. The symptoms led to marked dysfunction (Global Assessment of Functioning3 score = 30). She was diagnosed with paranoid schizophrenia (as per ICD-10 and DSM-IV) and was initially treated with risperidone (maximum dose = 6 mg/day, total duration of 24 months), trifluoperazine (maximum dose = 25 mg/day, total duration of 15 months), olanzapine (maximum dose = 25 mg/day, total duration of 4 months), and quetiapine (maximum dose = 600 mg/day, total duration of 4 months).
With each of these medications, Ms. A showed partial improvement initially (about 1 Clinical Global Impressions scale [CGI]4 point), with subsequent worsening to the previous level within a few weeks. As she (and her family) continued to refuse clozapine, she was switched to haloperidol (maximum dose = 30 mg/day, total duration of 2 months). She showed minimal initial improvement (1 CGI point) with haloperidol, so aripiprazole (maximum dose = 20 mg/day, total duration of 2 months) was added. With the combination of the 2 drugs, her symptoms worsened (2 CGI points) despite an increase in haloperidol dose (maximum = 60 mg/day). Ms. A started showing improvement in symptoms when aripiprazole was tapered off.
She maintained improvement on treatment with 60 mg/day of haloperidol over the next 5 months (about 3 CGI points beyond the level seen with the aripiprazole and haloperidol combination). According to her family, it was the best state achieved by the patient in the last 5 years. Objectively, her Positive and Negative Syndrome Scale5 positive syndrome score at this time was 0.
Aripiprazole acts as a D2 receptor antagonist in a hyperdopaminergic environment and as an agonist in a hypodopaminergic environment. In the index case, the presence of haloperidol, which is a potent D2 antagonist, led to a hypodopaminergic state. In the hypodopaminergic milieu, aripiprazole acted as an agonist and led to worsening of symptoms. This hypothesis can be more strongly accepted for the present case in particular, because withdrawal of aripiprazole led to improvement in psychotic symptoms. Our case is an addition to the small number of cases in which this phenomenon has been reported2,4,6,7 and suggests the need for caution while adding aripiprazole to augment the action of antipsychotics.