Risk of seizures associated with antipsychotic treatment in pediatrics with psychiatric disorders: a nested case–control study in Korea

Jeon, Soo Min; Park, Susan; Kim, Do-Hoon; Kwon, Jin-Won

doi:10.1007/s00787-020-01525-4

Cited by 10 publications

(10 citation statements)

References 41 publications

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“…Another previous study reported that the association between antipsychotic use and parkinsonism was more intensified in recently treated patients (28). Our previous study had also demonstrated that the current use of antipsychotics (within 90 days before the incidence date of seizures) had a greater risk of developing seizures than that of consistent use (>90 days before the incidence date of seizures) (12). Typical antipsychotic agents, including haloperidol, have a stronger affinity to dopaminergic D2 receptors than atypical antipsychotic agents (30,42); therefore, they are well-known to have a higher risk of developing movement disorders than atypical drugs.…”

Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

“…Antipsychotics treatment patterns, such as exposure time and drug dose, could be important factors for neurological adverse events. Previous studies on the neurological adverse events of antipsychotics have evaluated the use of antipsychotics at a specific time point or within a limited time period (12)(13)(14). However, physicians may change drug dosage or switch between antipsychotic agents at any time depending on the clinical response, which may affect the changes in the risk of antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

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Association Between Antipsychotic Treatment and Neurological Adverse Events in Pediatric Patients: A Population-Based Cohort Study in Korea

et al. 2021

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Background: Potential adverse effects might be caused by increasing the number of antipsychotic prescriptions. However, the empirical evidence regarding pediatric psychiatric patients is insufficient. Therefore, we explored the antipsychotic-induced adverse effects focusing on the neurological system.Method: Using the medical information of pediatric patients retrieved from the claims data of Health Insurance Review and Assessment in Korea, we identified those psychiatric patients who were started on antipsychotic treatment at age 2–18 years between 2010 and 2018 (n = 10,969). In this study, movement disorders and seizures were considered as major neurological adverse events. The extended Cox model with time-varying covariates was applied to explore the association between antipsychotic medication and adverse events.Findings: Total 1,894 and 1,267 cases of movement disorders and seizures occurred in 32,046 and 33,280 person-years, respectively. The hazard risks of neurological adverse events were 3–8 times higher in the exposed to antipsychotics period than in the non-exposure period. Among the exposure periods, the most dangerous period was within 30 days of cumulative exposure. High doses or polypharmacy of antipsychotics was associated with increased risks of neurological adverse events. Among individual antipsychotics, haloperidol showed the highest risk of developing movement disorders among the examined agents. Quetiapine showed a lower risk of developing movement disorders but a higher risk of developing seizures than risperidone.Conclusion: These findings suggest that antipsychotics should be used with caution in pediatric patients, especially regarding initial exposure, high dose, and polypharmacy.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association Between Antipsychotic Treatment and Neurological Adverse Events in Pediatric Patients: A Population-Based Cohort Study in Korea

et al. 2021

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“…Contrary to CLZ and QTP, although the seizure-inducing effect of BPZ has not been clarified in clinical or preclinical studies (there are no reports of the BPZ-induced seizure); however, the present demonstration suggests that long-term exposure to therapeutic-relevant concentration of BPZ possibly shifts to enhancement of seizure susceptibility via astroglial Cx43 upregulation in the plasma membrane. Indeed, generally, aripiprazole, which is similar structural derivate and pharmacodynamic profile with BPZ [ 18 , 83 ], is considered to be well tolerated; however, aripiprazole is independently associated with greater seizure risk which enhanced further with an increase in the number of other antipsychotics, including QTP [ 84 , 85 ]. It should be notable the accumulating clinical experience regarding BPZ-induced seizure reaction in the future.…”

Section: Discussionmentioning

confidence: 99%

Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43

Fukuyama

Okada

2021

IJMS

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Recently, accumulating preclinical findings suggest the possibility that functional abnormalities of tripartite synaptic transmission play important roles in the pathophysiology of schizophrenia and affective disorder. Therefore, to explore the novel mechanisms of mood-stabilizing effects associated with tripartite synaptic transmission, the present study determined the effects of mood-stabilizing antipsychotics, clozapine (CLZ), quetiapine (QTP) and brexpiprazole (BPZ), on the astroglial l-glutamate release and expression of connexin43 (Cx43) in the astroglial plasma membrane using cortical primary cultured astrocytes. Neither acute (for 120 min) nor subchronic (for 7 days) administrations of CLZ, QTP and BPZ affected basal astroglial l-glutamate release, whereas both acute and subchronic administration of CLZ, QTP and BPZ concentration-dependently enhanced astroglial l-glutamate release through activated hemichannels. Subchronic administration of therapeutic-relevant concentration of valproate (VPA), a histone deacetylase inhibiting mood-stabilizing antiepileptic drug, enhanced the stimulatory effects of therapeutic-relevant concentration of CLZ, QTP and BPZ on astroglial l-glutamate release through activated hemichannel. Subchronic administration of therapeutic-relevant concentration of CLZ, QTP and BPZ did not affect Cx43 protein expression in the plasma membrane during resting stage. After subchronic administration of VPA, acute and subchronic administration of therapeutic-relevant concentrations of CLZ increased Cx43 protein expression in the plasma membrane. Both acute administrations of therapeutic-relevant concentrations of QTP and BPZ did not affect, but subchronic administrations enhanced Cx43 protein expression in the astroglial plasma membrane. Furthermore, protein kinase B (Akt) inhibitor suppressed the stimulatory effects of CLZ and QTP, but did not affect Cx43 protein expression in the astroglial plasma membrane. These results suggest that three mood-stabilizing atypical antipsychotics, CLZ, QTP and BPZ enhance tripartite synaptic glutamatergic transmission due to enhancement of astroglial Cx43 containing hemichannel activities; however, the Cx43 activating mechanisms of these three mood-stabilizing antipsychotics were not identical. The enhanced astroglial glutamatergic transmission induced by CLZ, QTP and BPZ is, at least partially, involved in the actions of these three mood-stabilizing antipsychotics.

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“…The association between various antipsychotics and the development of seizures is also not widely known. The risk ratio of seizures is above 4, according to data from a nationwide database from South Korea from 2008 to 2018 [4]. Seizure risk was enhanced further with an increase in the number of antipsychotic drugs used.…”

mentioning

confidence: 99%

First do no harm: use off-label antipsychotic medication in children and adolescents with great caution

Hoekstra

Dietrich

2022

Eur Child Adolesc Psychiatry

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Risk of seizures associated with antipsychotic treatment in pediatrics with psychiatric disorders: a nested case–control study in Korea

Cited by 10 publications

References 41 publications

Association Between Antipsychotic Treatment and Neurological Adverse Events in Pediatric Patients: A Population-Based Cohort Study in Korea

Association Between Antipsychotic Treatment and Neurological Adverse Events in Pediatric Patients: A Population-Based Cohort Study in Korea

Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43

First do no harm: use off-label antipsychotic medication in children and adolescents with great caution

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