A case report of exacerbation of extrapyramidal symptoms following the switch from risperidone to paliperidone during valproate therapy

Abstract Background 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. Wh...

Full description

Saved in:
Bibliographic Details
Main Authors: Emi Hata, Masatoshi Miyauchi, Nobuhiko Noguchi, Takeshi Asami
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Psychiatry
Subjects:
Online Access:https://doi.org/10.1186/s12888-024-06456-x
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1841544380566994944
author Emi Hata
Masatoshi Miyauchi
Nobuhiko Noguchi
Takeshi Asami
author_facet Emi Hata
Masatoshi Miyauchi
Nobuhiko Noguchi
Takeshi Asami
author_sort Emi Hata
collection DOAJ
description Abstract Background 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. Case presentation. 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. Discussion 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. Conclusion 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.
format Article
id doaj-art-b3bfec5a22674d3fb55a9021d0e32d70
institution Kabale University
issn 1471-244X
language English
publishDate 2025-01-01
publisher BMC
record_format Article
series BMC Psychiatry
spelling doaj-art-b3bfec5a22674d3fb55a9021d0e32d702025-01-12T12:34:32ZengBMCBMC Psychiatry1471-244X2025-01-012511610.1186/s12888-024-06456-xA case report of exacerbation of extrapyramidal symptoms following the switch from risperidone to paliperidone during valproate therapyEmi Hata0Masatoshi Miyauchi1Nobuhiko Noguchi2Takeshi Asami3Department of Psychiatry, Yokohama City University School of MedicineDepartment of Psychiatry, Yokohama City University School of MedicineDepartment of Psychiatry, Yokohama City University School of MedicineDepartment of Psychiatry, Yokohama City University School of MedicineAbstract Background 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. Case presentation. 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. Discussion 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. Conclusion 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.https://doi.org/10.1186/s12888-024-06456-xPaliperidoneRisperidoneValproateExtrapyramidal SymptomsAntipsychotic SwitchingNeuroleptic Malignant Syndrome
spellingShingle Emi Hata
Masatoshi Miyauchi
Nobuhiko Noguchi
Takeshi Asami
A case report of exacerbation of extrapyramidal symptoms following the switch from risperidone to paliperidone during valproate therapy
BMC Psychiatry
Paliperidone
Risperidone
Valproate
Extrapyramidal Symptoms
Antipsychotic Switching
Neuroleptic Malignant Syndrome
title A case report of exacerbation of extrapyramidal symptoms following the switch from risperidone to paliperidone during valproate therapy
title_full A case report of exacerbation of extrapyramidal symptoms following the switch from risperidone to paliperidone during valproate therapy
title_fullStr A case report of exacerbation of extrapyramidal symptoms following the switch from risperidone to paliperidone during valproate therapy
title_full_unstemmed A case report of exacerbation of extrapyramidal symptoms following the switch from risperidone to paliperidone during valproate therapy
title_short A case report of exacerbation of extrapyramidal symptoms following the switch from risperidone to paliperidone during valproate therapy
title_sort case report of exacerbation of extrapyramidal symptoms following the switch from risperidone to paliperidone during valproate therapy
topic Paliperidone
Risperidone
Valproate
Extrapyramidal Symptoms
Antipsychotic Switching
Neuroleptic Malignant Syndrome
url https://doi.org/10.1186/s12888-024-06456-x
work_keys_str_mv AT emihata acasereportofexacerbationofextrapyramidalsymptomsfollowingtheswitchfromrisperidonetopaliperidoneduringvalproatetherapy
AT masatoshimiyauchi acasereportofexacerbationofextrapyramidalsymptomsfollowingtheswitchfromrisperidonetopaliperidoneduringvalproatetherapy
AT nobuhikonoguchi acasereportofexacerbationofextrapyramidalsymptomsfollowingtheswitchfromrisperidonetopaliperidoneduringvalproatetherapy
AT takeshiasami acasereportofexacerbationofextrapyramidalsymptomsfollowingtheswitchfromrisperidonetopaliperidoneduringvalproatetherapy
AT emihata casereportofexacerbationofextrapyramidalsymptomsfollowingtheswitchfromrisperidonetopaliperidoneduringvalproatetherapy
AT masatoshimiyauchi casereportofexacerbationofextrapyramidalsymptomsfollowingtheswitchfromrisperidonetopaliperidoneduringvalproatetherapy
AT nobuhikonoguchi casereportofexacerbationofextrapyramidalsymptomsfollowingtheswitchfromrisperidonetopaliperidoneduringvalproatetherapy
AT takeshiasami casereportofexacerbationofextrapyramidalsymptomsfollowingtheswitchfromrisperidonetopaliperidoneduringvalproatetherapy