Shaw Jonathan, Kim Ethan, Ton Emily, Lai Charles, Bota Peter, Allee Tina
School of Medicine, California University of Science and Medicine, Colton, CA 92324, USA.
The Internal Medicine Service, Loma Linda University Health, Loma Linda, CA 92354, USA.
Diseases. 2025 Aug 21;13(8):274. doi: 10.3390/diseases13080274.
Aripiprazole is a third-generation antipsychotic, approved in 2002, notable for its partial agonism of the Dopamine D2 receptor and lower risk of metabolic and extrapyramidal adverse effects. It is available in a long-acting injectable formulation, which is very useful for maintaining medication compliance, which is crucial for preventing recurrent psychotic episodes in patients. Additionally, the aripiprazole long-acting injectable is frequently combined with other antipsychotic medications in acute settings to manage refractory symptoms. However, there is limited literature regarding the psychopharmacology, efficacy, and adverse effect profiles of augmenting aripiprazole long-acting injectable with other antipsychotic medications. This narrative review intends to synthesize the existing literature on aripiprazole, its comparative affinity to the dopamine D2 receptor versus other antipsychotics, and the efficacy and side effect profiles of combining aripiprazole with other antipsychotics in the context of acute inpatient treatment for psychosis. Current literature on K values indicates that fluphenazine, pimozide, thiothixene, trifluoperazine, and perphenazine bind more strongly to dopamine D2 receptors than aripiprazole. However, there is a knowledge gap regarding antipsychotic polypharmacy with aripiprazole and these first generation antipsychotics, limiting the discussion of these drug combinations to theory. Additionally, the muscarinic effects of aripiprazole suggest the possibility of augmentation with clozapine or xanomeline-trospium, albeit the peer-reviewed literature on this was also limited. Overall, it is difficult to draw conclusions regarding best clinical practices for these scenarios, as the existing literature is contradictory. Nonetheless, the application of the dopamine and muscarinic pathway theories for schizophrenia opens venues for future research and consideration.
阿立哌唑是一种第三代抗精神病药物，于2002年获批，因其对多巴胺D2受体具有部分激动作用且代谢和锥体外系不良反应风险较低而闻名。它有长效注射剂型，这对于维持药物依从性非常有用，而药物依从性对于预防患者复发精神病性发作至关重要。此外，阿立哌唑长效注射剂在急性情况下常与其他抗精神病药物联合使用，以控制难治性症状。然而，关于将阿立哌唑长效注射剂与其他抗精神病药物联用的精神药理学、疗效和不良反应情况的文献有限。本叙述性综述旨在综合现有关于阿立哌唑的文献，其与其他抗精神病药物相比对多巴胺D2受体的亲和力，以及在精神病急性住院治疗背景下将阿立哌唑与其他抗精神病药物联合使用的疗效和副作用情况。当前关于K值的文献表明，氟奋乃静、匹莫齐特、硫利达嗪、三氟拉嗪和奋乃静比阿立哌唑与多巴胺D2受体的结合更紧密。然而，关于阿立哌唑与这些第一代抗精神病药物联用的多药治疗存在知识空白，这限制了对这些药物组合的讨论仅停留在理论层面。此外，阿立哌唑的毒蕈碱样作用提示了与氯氮平或曲司氯铵联用增强疗效的可能性，尽管关于此的同行评审文献也有限。总体而言，由于现有文献相互矛盾，很难就这些情况的最佳临床实践得出结论。尽管如此，多巴胺和毒蕈碱途径理论在精神分裂症中的应用为未来的研究和思考开辟了道路。
