Pasquier de Franclieu S, Germain C, Petitjean F
17(e) secteur de Psychiatrie Générale, Hôpital Sainte-Anne, 1, rue Cabanis, 75014 Paris, France.
Encephale. 2009 Oct;35(5):496-8. doi: 10.1016/j.encep.2008.06.019. Epub 2009 Jan 8.
Aripiprazole is an atypical antipsychotic with a pharmacological profile, different from other atypical antipsychotics. It is a high-affinity partial agonist at the dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2 receptors. It is associated with a good safety and tolerability profile including extrapyramidal side-effects.
CASE-REPORT: We report on a 37 year-old female patient with paranoid schizophrenia who developed Parkinsonian symptoms after one month of aripiprazole 10mg per day. She had been admitted to our unit for a psychotic episode with delusions of persecution and grandiosity. It was her second hospitalization. During the first hospitalization, seven years earlier, she had been treated with haloperidol. We do not have any information about the tolerability of that treatment. At the start, she received olanzapine with good tolerability but without efficacy on psychotic symptoms. After 4 weeks, we switched from olanzapine to risperidone 6 mg per day. After a few days, the patient developed severe Parkinsonian symptoms. We reduced the dose to 4 mg per day without any effect on the extrapyramidal symptoms.We decided to discontinue risperidone and to introduce aripiprazole 10mg per day. After one month, the patient developed severe Parkinsonian symptoms including hypertonia, akinesia, and shuffling gait. After reduction of the dose of Aripiprazole to 5mg per day, all the Parkinsonian symptoms had disappeared within 5 days without any other medication.
Few reports of Parkinsonian symptoms with aripiprazole have been published in the adult population. There is one report of Parkinsonian symptoms, associated with hypersalivation without akathisia, in a patient treated with 30 mg per day of aripiprazole. All the symptoms disappeared after a switch to olanzapine. The other cases have been reported when aripiprazole was associated with anti-depressant serotonin specific reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. One report has been published of a 16 year-old girl who had already developed extrapyramidal symptoms with olanzapine and risperidone. Another has been published concerning a 3 year-old child who had taken a half tablet of aripiprazole 15 mg.
We hypothesise that cytochrome P450 2D6 is implicated in this case-report because it is active in metabolizing aripiprazole. This patient could have been deficient in this enzyme, thus failing to metabolize aripiprazole at a normal rate.
阿立哌唑是一种非典型抗精神病药物,其药理特性与其他非典型抗精神病药物不同。它是多巴胺D2和5-羟色胺5-HT1A受体的高亲和力部分激动剂,以及5-羟色胺5-HT2受体的拮抗剂。它具有良好的安全性和耐受性,包括锥体外系副作用。
我们报告一名37岁的偏执型精神分裂症女性患者,在每天服用10mg阿立哌唑一个月后出现帕金森症状。她因迫害妄想和夸大妄想的精神病发作入住我们科室。这是她的第二次住院治疗。七年前她第一次住院时,接受过氟哌啶醇治疗。我们没有关于那次治疗耐受性的任何信息。开始时,她服用奥氮平,耐受性良好,但对精神病症状无效。4周后,我们将奥氮平换成每天6mg的利培酮。几天后,患者出现严重的帕金森症状。我们将剂量减至每天4mg,但对锥体外系症状没有任何效果。我们决定停用利培酮,开始每天服用10mg阿立哌唑。一个月后,患者出现严重的帕金森症状,包括肌张力亢进、运动不能和拖步。将阿立哌唑剂量减至每天5mg后,所有帕金森症状在5天内消失,无需使用其他药物。
在成人中,关于阿立哌唑引起帕金森症状的报道很少。有一篇报道称,一名每天服用30mg阿立哌唑的患者出现帕金森症状,并伴有流涎过多但无静坐不能,换用奥氮平后所有症状消失。其他病例报告是在阿立哌唑与抗抑郁药5-羟色胺特异性再摄取抑制剂或5-羟色胺-去甲肾上腺素再摄取抑制剂联用时出现的。有一篇报道是关于一名16岁女孩,她使用奥氮平和利培酮时已经出现锥体外系症状。另一篇报道是关于一名3岁儿童,他服用了半片15mg的阿立哌唑。
我们推测细胞色素P450 2D6与本病例报告有关,因为它在阿立哌唑的代谢中起作用。该患者可能缺乏这种酶,因此无法以正常速率代谢阿立哌唑。