Hata Emi, Miyauchi Masatoshi, Noguchi Nobuhiko, Asami Takeshi
Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, Kanagawa, 236-0004, Japan.
Sekizenkai Hinatadai Hospital, 1081 Ichizawacho, Asahi-Ku, Yokohama, Kanagawa, Japan.
BMC Psychiatry. 2025 Jan 9;25(1):29. doi: 10.1186/s12888-024-06456-x.
Paliperidone is a second-generation antipsychotic and the main active metabolite of risperidone, formulated to provide consistent therapeutic effects through an extended-release system, designed to provide consistent therapeutic effects through an extended-release formulation. While commonly used in clinical practice, switching from risperidone to paliperidone, particularly during valproate therapy, can pose challenges due to potential pharmacokinetic interactions that may increase the risk of extrapyramidal symptoms (EPS). Despite clinical observations suggesting these interactions, case reports documenting such adverse effects are scarce.
We report a case of a 48-year-old Japanese male with epilepsy-associated psychosis and mild intellectual disability who experienced severe EPS during a gradual cross-titration from risperidone to paliperidone while on valproate therapy. The patient had a history of well-controlled epilepsy with valproate and developed auditory hallucinations, delusions, and psychomotor agitation at age 48. Initial treatment with risperidone was partially effective but did not sufficiently manage his psychotic symptoms, prompting a switch to paliperidone. Shortly after increasing the paliperidone dose, the patient developed significant EPS, including muscle rigidity and elevated creatine kinase levels, indicative of potential neuroleptic malignant syndrome. Paliperidone was immediately discontinued, leading to a marked improvement in symptoms.
This case highlights the pharmacokinetic interaction between valproate and paliperidone, which can elevate plasma levels of paliperidone and exacerbate EPS. Literature suggests that valproate can prolong the gastrointestinal retention time of paliperidone, leading to increased absorption and enhanced dopaminergic blockade. The gradual cross-titration method may have compounded these effects, emphasizing the need for careful dose adjustments and monitoring during antipsychotic switching, especially in patients on concomitant valproate therapy.
The findings suggest that direct substitution methods, rather than gradual cross-titration, may be safer when switching from risperidone to paliperidone, particularly in patients receiving valproate. Clinicians should be aware of the potential interactions and closely monitor for signs of EPS during such therapy adjustments.
帕利哌酮是第二代抗精神病药物，也是利培酮的主要活性代谢产物，其通过缓释系统来提供持续的治疗效果。虽然在临床实践中常用，但从利培酮转换为帕利哌酮时，尤其是在丙戊酸盐治疗期间，由于可能存在的药代动力学相互作用，可能会增加锥体外系症状（EPS）的风险，从而带来挑战。尽管临床观察提示了这些相互作用，但记录此类不良反应的病例报告却很稀少。
我们报告了一例48岁的日本男性病例，该患者患有癫痫相关性精神病和轻度智力残疾，在丙戊酸盐治疗期间从利培酮逐渐交叉滴定至帕利哌酮的过程中出现了严重的EPS。该患者有使用丙戊酸盐良好控制癫痫的病史，48岁时出现幻听、妄想和精神运动性激越。最初使用利培酮治疗部分有效，但未能充分控制其精神病症状，促使改用帕利哌酮。增加帕利哌酮剂量后不久，患者出现了明显的EPS，包括肌肉僵硬和肌酸激酶水平升高，提示可能存在神经阻滞剂恶性综合征。立即停用帕利哌酮后，症状明显改善。
该病例突出了丙戊酸盐与帕利哌酮之间的药代动力学相互作用，这可能会提高帕利哌酮的血浆水平并加重EPS。文献表明，丙戊酸盐可延长帕利哌酮在胃肠道的滞留时间，导致吸收增加和多巴胺能阻滞增强。逐渐交叉滴定法可能使这些效应更加复杂，强调了在抗精神病药物转换期间，尤其是在接受丙戊酸盐治疗的患者中，需要仔细调整剂量并进行监测。
研究结果表明，从利培酮转换为帕利哌酮时，直接替代法而非逐渐交叉滴定法可能更安全，尤其是在接受丙戊酸盐治疗的患者中。临床医生应意识到潜在的相互作用，并在此类治疗调整期间密切监测EPS的迹象。
