Inadvertent High-Dose Exposure to Paliperidone Palmitate Depot: A Case Report

Inadvertent High-Dose Exposure to Paliperidone Palmitate Depot: A Case Report | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 14 September 2025 V1 Latest version Share on Inadvertent High-Dose Exposure to Paliperidone Palmitate Depot: A Case Report Authors : Ashna Khalid 0009-0009-1791-0231 [email protected] , Samuel Sebastian , Preston Yang , Aafreen Khalid , and Harish Chikanna Authors Info & Affiliations https://doi.org/10.22541/au.175787115.51396090/v1 429 views 139 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Paliperidone palmitate is an atypical antipsychotic that can be administered via intramuscular route in one monthly, three monthly and six monthly preparations. Accidental overdose of paliperidone has been reported on several occasions, however the existing published literature only repots on overdoses occurring from cumulative doses over a period of time. We report the case of a 55-year-old male with schizophrenia, admitted with a psychotic relapse and, overdue for his paliperidone three monthly long acting injectable (LAI) 350mg, who inadvertently received 350mg of the 1-monthly preparation in one single administration. Side effects were monitored over a three week period in the inpatient setting during which there were only mild reports of extra-pyramidal side effects. The patient continued to receive follow up through the community mental health team for 6 months with no further adverse effects reported. Inadvertent High-Dose Exposure to Paliperidone Palmitate Depot: A Case Report Running title: High-Dose Paliperidone Depot Exposure Ashna Khalid 1,2 , Samuel Sebastian 1 , Preston Yang 1 , Aafreen Khalid 2,3 , Harish Chikanna 1 1 Mercy Mental Health, Werribee Mercy Hospital, Hoppers Crossing, Victoria, Australia 2 Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia 3 Central Adelaide Local Health Network, The Royal Adelaide Hospital, Adelaide, SA, Australia Corresponding author: Ashna Khalid, Mercy Mental Health, Werribee Mercy Hospital, 300 Princes Highway, Werribee, VIC 3030, Australia Email: [email protected] Abstract: Paliperidone palmitate is an atypical antipsychotic that can be administered via intramuscular route in one monthly, three monthly and six monthly preparations. Accidental overdose of paliperidone has been reported on several occasions, however the existing published literature only repots on overdoses occurring from cumulative doses over a period of time. We report the case of a 55-year-old male with schizophrenia, admitted with a psychotic relapse and, overdue for his paliperidone three monthly long acting injectable (LAI) 350mg, who inadvertently received 350mg of the 1-monthly preparation in one single administration. Side effects were monitored over a three week period in the inpatient setting during which there were only mild reports of extra-pyramidal side effects. The patient continued to receive follow up through the community mental health team for 6 months with no further adverse effects reported. Key words: antipsychotic, depot, paliperidone palmitate, overdose Word count: 1982 words What is known about this subject • Paliperidone palmitate is the only long-acting injectable antipsychotic available in monthly, three-monthly, and six-monthly preparations, widely used for schizophrenia and related disorders • Overdose of paliperidone palmitate is rare, with most reported cases involving cumulative dosing over several days or weeks, rather than a single administration event • Documented adverse effects of paliperidone palmitate include extrapyramidal symptoms, sedation, and cardiovascular effects; however, these have been non-fatal What this study adds • This report describes the first known case of a single, inadvertent high-dose administration of monthly paliperidone palmitate in a patient with schizophrenia. • Despite exceeding the recommended maximum dose, the patient experienced only mild, transient extrapyramidal symptoms and no serious or lasting adverse effects during both inpatient and community long term follow-up. • It suggests that there is limited additional therapeutic benefit with dosing this medication above current recommendations. Introduction: Monthly long acting injectables (LAI), informally knows as ‘depot’ medication, such as that of paliperidone, are suitable treatment options for a range of psychiatric conditions including schizophrenia and schizoaffective disorder. It may be used as monotherapy or in combination with antidepressants and mood stabilisers, depending on the clinical context. Paliperidone palmitate does not require refrigeration and is the only antipsychotic LAI that is available in a monthly (PP1M), three monthly (PP3M) and six monthly (PP6M) preparation(1). By maintaining therapeutic plasma levels within the intervals of injections, it provides effective treatment(2). Intramuscular (IM) route of administration can provide optimal adherence to dose regimens prescribed with administration and documentation by a clinician on a routine basis. There is also reduced risk of noncompliance by replacing daily oral administration which may contribute to the achieved efficacy of IM antipsychotics. Systematic reviews demonstrated this when comparing oral and depot treatment in the outpatient setting with relative and absolute risk reductions of 30% and 10% respectively (RR 0.70, CI 0.57-0.87, NNT 10, CI 6-25, P=0.0009)(3). Side effects of paliperidone LAI include extra-pyramidal side effects which have been reported to demonstrate a dose dependent relationship(4). Where common side effects are known, there are only a few reports on the outcomes of paliperidone palmitate overdosing, most commenting on staggered doses over a short period of time, rather than an overdose administered on one isolated occasion(5, 6). In this paper we describe an accidental paliperidone palmitate overdose in a single administration event, including the short and long term management approach and respective outcomes. Case summary: A 55-year-old male with a diagnosis of schizophrenia was under the care of the local community mental health team for several years. His past medical history included gastro-oesophageal reflux disease and treated hepatitis C. Regular medications were perindopril 5 mg daily, amlodipine 5 mg daily, cholecalciferol 25 mcg daily, esomeprazole 20 mg daily, pregabalin 150 mg daily, and paliperidone palmitate 350 mg IM every three months. He reported regular use of cannabis and methamphetamines. The patient was admitted to hospital with relapse of his symptoms in the context of avoidance of paliperidone palmitate 3-monthly (PP3M) and overdue for 28 days. The presentation was further exacerbated by substance use. He expressed feeling threatened by his neighbours and was paranoid. His admission vital signs assessment were within normal range. Physical examination was unremarkable aside from minor bleeding from forehead wounds from head banging at home. Mental state examination showed he was occasionally loud, disruptive, irritable, with disorganised thinking, paranoid themes and passive suicidal ideation. His regular depot injection was prescribed on initial psychiatrist review, however stock of PP3M was unavailable. Despite two nursing checks of the written prescription, he inadvertently received 350 mg of PP1M instead of the intended PP3M, where the highest dose recommended for PP1mg is around 234mg(7). This was immediately recognised with open disclosure, physical assessment and medical consultation. Sedative medications were ceased, and the toxicology team was consulted and recommended close monitoring. Observations were performed; including Abnormal Involuntary Movement Scale (AIMS) scores which were normal, except for mild mouth movements. The patient reported dry mouth but was otherwise asymptomatic during the first week. Electrocardiogram (ECG) and blood tests were encouraged, however the patient consistently refused this. As required benztropine oral and IM was charted, however this was not required, nor utilised. Over the following one to two weeks, the patient remained physically stable. AIMS scores were monitored weekly, with a transient mild involuntary tongue movement noted on day seven (AIMS score one). Observations were reduced from daily to twice daily, then twice weekly. Regarding physical health events, he experienced an episode of minor bleeding from head banging on day eight and one episode of self-resolving chest pain on day 13 with negative troponin assays and nil ECG changes. Ongoing assessment showed mild tongue fasciculations but otherwise normal neurological and physical examination with AIMS score between zero to two for the second week of admission. Chronic persecutory delusions persisted throughout the admission. A second loading dose of paliperidone palmitate 100mg was administered on day 21. Risperidone levels were taken on this day with risperidone 20-60 ug/L)(8). General blood count, electrolytes and renal function were generally within range and prolactin measured was 718 mIU/L. ECG was obtained which was sinus rhythm with a corrected QT interval of 426ms, which was repeated four days later with the same result. The patient was discharged on day 24 but re-presented to the emergency department within 24 hours with ongoing persecutory delusions. As paliperidone was deemed ineffective in achieving adequate symptom control, he was commenced on oral haloperidol and then initiated on haloperidol LAI 50mg fortnightly on day 40 with paliperidone ceased. There was lack of engagement with the community team following discharge with mostly phone reviews and home visits for depot administration. Subsequently, haloperidol depot was changed to 150mg four weekly. At the 6 month mark, there were no subjective reports of side effects, AIMS scores were not reported and the patient did not agree to further blood monitoring or ECGs. His mental state improved with complete resolution of paranoid delusions, reduced intensity of suicidal ideation, and improved clarity to his thought stream. Discussion: Paliperidone palmitate is a LAI atypical antipsychotic with established efficacy and tolerability in the management of schizophrenia and related psychotic disorders(9, 10). Paliperidone’s primary mechanism of action involves antagonism of dopamine D2 and serotonin 5-HT2A receptors, which underpins its effect in treating psychotic illness but also D2 mediated extrapyramidal side effects via the nigrostriatal pathway(11). It also exhibits antagonistic activity at alpha-adrenergic and histaminergic receptors, further contributing to its side effect spectrum with sedation, and orthostatic hypotension and tachycardia respectively(1). Paliperidone has minimal affinity for muscarinic cholinergic receptors, resulting in a lower risk of anticholinergic side effects and cognitive impairment compared to risperidone(12). Earlier studies on cumulative paliperidone oral tablet overdoses confirm the above adverse events with dose dependent relationship in relation to both EPSE and cardiovascular changes including narrow complex tachycardia(13). These findings has been similarly observed through the use of LAIs in several case studies including with Ojimba’s observation of a 21 year old with cumulative dose of PP1M 625mg over 11 days and Nersesjans’ case report on chronic accumulation of PP1M over 8 years, noting dystonia reduced in line with the gradual reduction in plasma concentrations of paliperidone(6, 14) . These events of overdose in the literature have been non fatal. While several cases of paliperidone palmitate LAI cumulative overdoses have been reported in the literature, to our knowledge, this is the first documented case of an overdose involving a single administration event of the PP1M formulation. In this instance, the patient was closely monitored in an inpatient setting for 25 days, corresponding to the anticipated period of highest risk for adverse effects, as determined by the pharmacokinetic half-life and expected peak level of the medication(15). Known dose related and extrapyramidal side effects (EPSEs) were captured through the relevant monitoring tools including the AIMS assessment (for EPSEs), vital sign assessment (for hypotension) and subjective reports (for non-specific dizziness). Reassuringly, no haemodynamic instability was noted with serial vital sign assessment in the inpatient admissions, nor were there any major adverse effects were observed during this period. As a result, there was no need for the use of anticholinergics such as benztropine, though charting this in anticipation was one strategy to address the risk. A similar case report on cumulative overdose PP1M over five days also showed no medical consequence or major EPSE that was similarly managed with monitoring, with no need for pharmacological intervention (16). Despite the over-administration of paliperidone in this clinical case, there was no significant reduction in the symptom burden during the two to three week admission and following discharge after the second loading dose. This may be related to the patient’s individual response to paliperidone, possible fast metabolisation of paliperidone or rapid renal excretion. However, we have no pharmacogenomic testing to confirm this and there was no known renal impairment. Current studies confirm the limited additional therapeutic benefit with administration of doses beyond the currently accepted maximum dose of 234mg for PP1M, which is supported by this case scenario as well(7). This case report however remains limited by the lack of regular objective monitoring, such as baseline and repeat serum risperidone levels, serum prolactin and ECG which may have provided additional insights into the pharmacodynamic response. There remains scope for the development of guidelines post overdose of IM antipsychotic treatment, as there is limited information available which informs current management. Conclusion: This case highlights the clinical course and management of an unintentional overdose of paliperidone palmitate in a patient with schizophrenia. Despite over administration of PP1M, the patient experienced only mild and transient extrapyramidal symptoms, with no severe or lasting adverse effects observed during inpatient monitoring and community follow up. This outcome is consistent with previous reports suggesting that paliperidone palmitate is generally well tolerated, even at supratherapeutic doses, and also reflecting limited perceived benefit to symptom burden beyond the current recommended maximum doses. Author contributions: The authors confirm that the principle investigator for this paper is Dr Harish Chikanna and that Dr Chikanna had direct clinical responsibility for the patient. All authors have read, critical reviewed and approved the submitted case. Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. Funding: The author(s) received no financial support for the research, authorship and/or publication of this article. Ethical statement: Ethical approval for this case report was obtained by the Executive of the St Vincent’s Hospital (Melbourne) Human Research Ethics Committee (HREC). The author(s) obtained verbal and written consent from the patient for author(s) to use de-identified information in the described case report and for the case report to be published in an academic journal. The case report ORCID ID: Ashna Khalid - https://orcid.org/0009-0009-1791-0231 Preston Yang - https://orcid.org/0009-0003-7965-0136 Aafreen Khalid - https://orcid.org/0000-0003-2724-9773 References: 1. Citrome L. Paliperidone palmitate - review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication. Int J Clin Pract. 2010;64(2):216-239. doi:10.1111/j.1742-1241.2009.02240.x 2. Correll CU, Johnston K, Turkoz I, Gray J, Sun L, Doring M, Sajatovic M. Three-year outcomes of 6-month paliperidone palmitate in adults with schizophrenia: an open-label extension study of a randomized clinical trial. JAMA Netw Open. 2024;7(7):e2421495. doi:10.1001/jamanetworkopen.2024.21495 3. Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S. 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Schizophr Res. 1991;4(2):121-156. doi:10.1016/0920-9964(91)90030-u 12. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996;124(1-2):57-73. doi:10.1007/BF02245606 13. Levine M, Lovecchio F, Tafoya P, Graham R. Paliperidone overdose with delayed onset of toxicity. Ann Emerg Med. 2011;58(1):80-82. doi:10.1016/j.annemergmed.2010.10.015 14. Nersesjan M, Wagner M, Dalhoff KP, Petersen TS, Bøgevig S, Horwitz H. Paliperidone poisoning and measurable plasma concentrations 2.5 years after last administered dose: a case report. Br J Clin Pharmacol. 2023;89(2):1070-1073. doi:10.1111/bcp.16036 15. Samtani MN, Vermeulen A, Stuyckens K. Population pharmacokinetics of intramuscular paliperidone palmitate in patients with schizophrenia: a novel once-monthly, long-acting formulation of an atypical antipsychotic. Clin Pharmacokinet. 2009;48(9):585-600. doi:10.2165/11316870-000000000-00000 16. Vannucchi T, Gemignani S, Ricca V, Cardamone G. Safety and tolerability of paliperidone palmitate: a case report of an accidental overdose. J Psychopathol. 2020;26:163-166. doi:10.36148/2284-0249-401 Information & Authors Information Version history V1 Version 1 14 September 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Ashna Khalid 0009-0009-1791-0231 [email protected] Werribee Mercy Hospital View all articles by this author Samuel Sebastian Werribee Mercy Hospital View all articles by this author Preston Yang Werribee Mercy Hospital View all articles by this author Aafreen Khalid The University of Adelaide Adelaide Medical School View all articles by this author Harish Chikanna Werribee Mercy Hospital View all articles by this author Metrics & Citations Metrics Article Usage 429 views 139 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ashna Khalid, Samuel Sebastian, Preston Yang, et al. Inadvertent High-Dose Exposure to Paliperidone Palmitate Depot: A Case Report. Authorea . 14 September 2025. DOI: https://doi.org/10.22541/au.175787115.51396090/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. 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