Manifestation of Extrapyramidal Symptom and Seizure in Accidental Haloperidol Ingestion
Received Date: Jul 12, 2018 / Accepted Date: Jul 17, 2018 / Published Date: Jul 26, 2018
Haloperidol is a typical antipsychotic drug used in the treatment of various psychiatric conditions with schizophrenia and anxiety being its common indications. Like other typical agents, its affinity for D2 receptor antagonism imparts it adverse effects such as extrapyramidal symptoms (EPS), parkinsonism and dyskinesia. Previous literature suggests paediatric haloperidol toxicity is rare, however, when it occurs, it presents with EPS, altered blood pressure and impaired consciousness and is rarely associated with seizures. The current case outlines one incident of haloperidol toxicity in a child associated with seizures the subsequent successful therapeutic approach used for management.
Keywords: Haloperidol; Toxicity; Paediatrics; Extrapyramidal Symptom; Seizure
Haloperidol is a drug belonging to butyrophenone class of typical antipsychotics with dominant antipsychotic and anti-anxiety effects used mainly in the treatment of schizophrenia, acute psychosis, Tourette syndrome, delirium, agitation and hallucinations associated with alcohol withdrawal. It is derived from Meperidine and Paul Janssen has been lauded with its discovery. Considered a relatively safe drug, common side-effects associated with haloperidol include extrapyramidal symptoms (EPS), which are one of the classic manifestations of the typical antipsychotics in contrast to the atypical ones and occur frequently in patients on therapy for schizophrenia and anxiety. EPS refers to a collection of adverse movement disorders, including akathisia, tardive dystonia, dystonic reactions, tremor, muscle spasm, rigidity, anticholinergic effects and convulsions .
Blockade of the D2 receptors induces extrapyramidal effects. Repeated administration causes an increase in D2-receptor sensitivity due to an increase in abundance of these receptors. This appears to underlie the tardive dyskinesia that is caused by prolonged use of the conventional antipsychotic drugs. Most antipsychotic agents which possess antagonistic effect on this receptor tend to produce EPS, akathisia, long term tardive dyskinesia and hyperprolactinemia. The severity of such symptoms is dependent on the affinity for D2 receptor antagonism and the risk is higher in younger patients with peak incidences between 10 to 19 years. The dystonia is typically manifested in the neck muscles and tongue and may lead to oculogyric crisis, extraocular muscles which are its more severe outcomes .
There is little in the way of epidemiological evidence which considers the incidences of haloperidol toxicity. However, an extensive review of the literature reveals that there been even fewer reported incidences of haloperidol poisoning in children . Scialli and Thornton reported fourteen unpublished cases, revealed from direct communication with McNeil laboratories in which the following manifestations were seen: nine children with impaired conscious, seven with EPS, two with hypertension and one child with no obvious symptoms . They further present two siblings with high-dose haloperidol ingestion who presented with unusual thermal-cardiac manifestations, including brady and tachycardia, hypotension and hypothermia . Yoshida et al. discuss a further 24 cases where children suffered acute haloperidol overdose after a medication error . Of the 24 children presented with a variety of clinical symptoms: 24 with disturbed consciousness, 16 with tremors in the extremities, 14 with an oculogyric crisis or similar, nine with dysarthria, eight with drooling and six with akathisia, six with hyperreflexia and three with opisthotonos. As demonstrated, typical manifestations of haloperidol toxicity in children involve EPS, altered blood pressure, sedative effects and altered consciousness. Furthermore, haloperidol toxicity has been associated with a low risk of seizure provocation . With this in mind, we present the following case of a child who presented to the emergency department of a tertiary care super-speciality hospital with seizures after an acute haloperidol overdose.
A 2-year-old female patient was brought into with complaints of 3 episodes of seizure at an interval of 5 minutes. The parents also complained about abnormal movements associated with neck and head of the child. The child was found to be having weight of 14 kg which indicated adequate nourishment. Upon examination, the child was found to have elevated blood pressure (140/85 mmHg) with the remaining vitals normal. The eyes were found to have been deviated to an upward gaze and generalized hypertonia was observed. The patient was drowsy and disoriented with symptoms of a focal seizure. Deep reflexes were however found to be intact and the overall picture gave an indication of extrapyramidal manifestations. The parents suspected of accidental medication ingestion as stated by the elder sibling (5 years) who said to have seen the patient drinking from the medication bottle they had brought along. The medication label indicated the ingested syrup to be Haloperidol and the parents stated that it was being consumed by the patient’s grandmother who had been suffering from schizophrenic episodes for the past 6 months. The physician diagnosed the patient with having haloperidol induced extrapyramidal symptom and the child was immediately moved into the paediatric ICU. Activated charcoal at a dose of 10 g was given through nasogastric tube to detoxify the ingested drug by adsorption. An I.V. line was established and the patient was given fluid and electrolyte supplements. Fosphenytoin 50 mg was administered through slow I.V. in a STAT dose to subdue a second wave of seizure. Haematological tests and electrocardiogram were ordered for the patient with the results indicating no abnormalities. The patient was initiated on Promethazine 0.1 mg/kg and Trihexyphenidyl 2 mg/TID. After two and a half days of intensive therapeutic monitoring, the patient was stabilized and was discharged with paediatric multivitamin drops and glycerol suppository to be given as required against constipation.
This case demonstrates the necessity in considering accidental drug toxicity in any new presentation of new-onset seizures in a young child. A high clinical suspicion of drug toxicity should be held with any patients presenting with symptoms of acute dystonia involving muscle, neck and tongue spasm, tremor, oculogyric crisis as evidenced by upwards gaze, as seen in our patient. The presence of seizures, while rare should also alert physicians to drug toxicity. Among the first generation antipsychotics, the highly potent haloperidol is usually associated with the highest risk of extrapyramidal symptoms. A systematic review found that 21 to 31 percent of patients treated with haloperidol for three to eight weeks experienced drug-induced extrapyramidal symptoms . Oral absorption of the drug may be erratic undergo extensive first-pass metabolism by the liver, yielding low or variable oral bioavailability. Also are lipophilic, highly proteinand tissue-bound as a class with large volumes of distribution. Each of these factors varies substantially among patients, making it difficult to predict serum drug levels based on dose alone [8,9]. A 2015 nested case-control analysis of over 60,000 patients from the United Kingdom found that the risk of seizure with First Generation Antipsychotics was 49.4 per 10,000 person-years of exposure to chlorpromazine and thioridazine, and 59.1 for haloperidol and trifluoperazine, compared with 11.7 for control patients .
In this case, there was an initial confusion whether the patient had a seizure or if the combination of tremor with dystonia resulted in a pseudo-seizure. However, given the immediate stabilization of the patient by Fosphenytoin administration, it indicates that a true seizure occurred. Again, this demonstrates the importance of treating pseudoseizures, with a relatively safe agent, rather than waiting to confirm the diagnosis at the risk of permanent cognitive impairment in the patient. Treating the EPS manifestations should be done with anticholinergic agents such as benztropine (Cogentin), diphenhydramine (Benadryl), and trihexyphenidyl (Artane). Other common causes of treatment include dopamine agonist agents, such as pramipexole. These medications reverse the EPS caused by antipsychotics or other drugs which inhibit dopaminergic neurotransmission . Literature shows that haloperidol induced dystonia occurs more often in children. There are reports of delayed onset of hypertension; hence inpatient observation of children with accidental haloperidol poisoning is recommended .
While we were unable to establish the dose consumed by the patient in this case, it appears likely that a single mouthful of the haloperidol may be sufficient to have caused at least some of the symptoms demonstrated. In paediatric patients with psychiatric manifestation, the maximal dose (assuming a child of 40 kg weight with severe disease manifestations), is 6 mg of haloperidol, after which there is little benefit and side-effects will outweigh the benefits conferred. We suspect the patient may have consumed far in excess of the 6 mg, however, despite the excessive dose consumed, there were fortunately no mortally dangerous symptoms like neuroleptic malignant syndrome or other permanent brain trauma as sequalae.
As the incidence of haloperidol toxicity is uncommon in children, the optimal approach appears to be the use of activated charcoal, as well as supportive and symptomatic management, according to guidelines, with a minimum of two days of intensive monitoring once the patient has been stabilized to minimize risk from further manifestations. In future, we recommend that patients who are prescribed any drugs should be reminded that their medication should not be left astray in houses, especially those with children and that caution should be exercised, in general. Additionally, this case demonstrates that when one is the diagnosis in younger patients presenting with new-onset symptoms, such as seizures, the importance of taking through medical, social and family history, especially a family drug history is should not be undermined. This will help establish whether the presentation is that of a true disease or is occurring as a manifestation of some other causative agent.
Conflict of interest
There is no conflict of interest.
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Citation: Salim MKT (2018) Manifestation of Extrapyramidal Symptom and Seizure in Accidental Haloperidol Ingestion. Epilepsy J 4: 129. DOI: 10.4172/2472-0895.1000129
Copyright: © 2018 Salim MKT. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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