Department of Psychiatry, Chiba University Graduate School of Medicine.
Division of Medical Treatment and Rahabilitation, Chiba University Center for Forensic Mental Health.
Int Clin Psychopharmacol. 2020 Nov;35(6):338-344. doi: 10.1097/YIC.0000000000000322.
Dopamine supersensitivity psychosis (DSP) in patients with schizophrenia is induced by treatment with a high dosage of antipsychotics for a long time period, and it is characterized by unstable psychotic symptoms. The upregulation of dopamine D2 receptor (DRD2) provoked by antipsychotics underlies DSP. Aripiprazole does not cause an excessive blockade of DRD2 and is less likely to upregulate DRD2 by aripiprazole's dopamine partial agonistic profile. Aripiprazole; however, has a potential risk of inducing severe rebound psychosis in patients who have already developed dopamine supersensitivity. Recently, an animal model study suggested that aripiprazole could attenuate established dopamine supersensitivity. The present study was conducted to examine whether very slowly switching to aripiprazole could help patients with schizophrenia with dopamine supersensitivity while avoiding rebound psychosis. This study was a single-armed and open-labeled study in which patients were observed over a period of 2 years. Only 11 patients were ultimately recruited. Five patients were successfully switched to a sufficient dose of aripiprazole and completed the study protocol. These five patients did not present with severe DSP over the study period, but only one patient showed a large improvement in psychopathology. Five patients dropped out of the study, and one of these five showed a severe worsening of psychosis. The present study indicated that the introduction of aripiprazole in patients with DSP was difficult, but suggested that aripiprazole could contribute to attaining a stable state in psychosis if it was applied with careful observation.
精神分裂症患者的多巴胺超敏性精神病（DSP）是由长期高剂量抗精神病药物治疗引起的，其特征为不稳定的精神病症状。抗精神病药物引起的多巴胺 D2 受体（DRD2）上调是 DSP 的基础。阿立哌唑不会引起 DRD2 的过度阻断，并且由于其多巴胺部分激动作用，阿立哌唑不太可能上调 DRD2。然而，阿立哌唑有在已经出现多巴胺超敏的患者中引发严重反弹精神病的潜在风险。最近的一项动物模型研究表明，阿立哌唑可以减轻已建立的多巴胺超敏。本研究旨在研究以非常缓慢的速度转换为阿立哌唑是否可以帮助患有多巴胺超敏的精神分裂症患者，同时避免反弹精神病。这是一项单臂、开放标签的研究，患者在 2 年内接受观察。最终仅招募了 11 名患者。5 名患者成功转换为足够剂量的阿立哌唑并完成了研究方案。这些 5 名患者在研究期间没有出现严重的 DSP，但只有 1 名患者的精神病理学有较大改善。5 名患者退出了研究，其中 1 名患者的精神病恶化严重。本研究表明，在 DSP 患者中引入阿立哌唑较为困难，但表明如果仔细观察，阿立哌唑可能有助于达到稳定的精神病状态。
