Brexpiprazole toxicity in a paediatric patient.

Brexpiprazole is a relatively new drug that has no published research or applications within the paediatric population. Brexpiprazole targets multiple receptors and can manifest as multisystem symptoms when ingested in supratherapeutic quantities. In this report, we discuss the case of a child in early childhood who presented with delayed neurological and cardiac symptoms 24 hours after accidental ingestion of brexpiprazole. Due to delayed onset, this case highlights that a high index of suspicion and prolonged observation are necessary to appropriately manage brexpiprazole overdose or accidental ingestion.

Risk assessment of isolated aripiprazole exposures and toxicities: a retrospective study.

STUDY OBJECTIVE: To characterize the clinical effects of acute isolated aripiprazole poisonings and to assess the toxic dose of this drug. METHODS: All isolated acute aripiprazole exposures reported to a poison control system from January 2002 through September 2006 were retrospectively reviewed. Patients with incomplete information or those lost to follow-up were excluded. RESULTS: A total of 286 cases were identified. Mean age was 18.9 years (SD 15.7), with a range of 6 months-70 years. Seventy-seven patients (27%) were or=18 years. Doses were known in 255 patients (89%). Symptoms occurred in 158 patients (55%): somnolence 89 (56%), tachycardia 32 (20%, heart rate 102-186), nausea/vomiting 29 (18%), dystonic reactions 21 (13%), tremor 9 (6%), agitation 3 (2%), dizziness 3 (2%), paresthesia 2 (1%), headache 2 (1%), dysphagia 1 (<1%), syncope 1 (<1%), minor facial swelling 1 (<1%), and hypotension 1 (<1%). None of the patients required intubation, and there were no deaths or EKG abnormalities. Median dose for symptomatic and asymptomatic groups were 25 and 15 mg, respectively, for or=18 (p = 0.25). In comparison of drug groups (Group 1, or=91 mg), symptoms were more likely to occur in Group 2 versus Group 1 (OR 2.29, 95% CI 0.79-6.61) in patients or=18 years. CONCLUSIONS: Acute aripiprazole poisonings most commonly result in sedation, sinus tachycardia, nausea/vomiting, or dystonic reactions. Symptoms are more likely with doses above 90 mg, although pediatric patients can be affected at a lower dose.

A systematic review of cardiovascular effects after atypical antipsychotic medication overdose.

As the use of atypical antipsychotic medications (AAPMs) increases, the number of overdoses continues to grow. Cardiovascular toxicity was common with older psychiatric medications but seems uncommon with AAPM. We conducted a systematic literature review to describe the cardiovascular effects reported after overdose of 5 common AAPM: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. We included case reports and case series describing overdose of these 5 medications identified in a search of MEDLINE, EMBASE, and abstracts from major toxicology meetings. We found 13 pediatric cases (age, <7 years), 22 adolescent cases (age, 7-16 years), and 185 adult cases. No pediatric case described a ventricular dysrhythmia or a cardiovascular death. In the adolescent and adult cases, we found numerous reports of prolonged corrected QT interval and hypotension, but there were only 3 cases of ventricular dysrhythmia and 3 deaths that may have been due to direct cardiovascular toxicity. The results from case series reports were similar to the single case report data. Our review suggests that overdose of AAPM is unlikely to cause significant cardiovascular toxicity.

Prolonged toxicity in a 2-year-old after accidental ingestion of aripiprazole.

Aripiprazole (Abilify), or 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy}-3,4-dihydro-2(1H)-quinolone, is a novel atypical antipsychotic possessing a long half-life. Although not a Food and Drug Administration-approved indication, low-dose aripiprazole is used to treat pediatric psychiatric conditions. Data regarding toxicity of low-dose aripiprazole ingestions in children are limited. We report the case of an accidental ingestion of two 5-mg aripiprazole tablets by a 2-year-old girl with a measured drug level of 160 ng/mL approximately 34 hours after ingestion. She exhibited marked lethargy, tremor, and tachycardia persisting over 72 hours. Emergency physicians, pediatricians, and psychiatrists should be aware of the potential for significant and prolonged toxicity in children even with relatively small-dose aripiprazole exposures.

Aripiprazole exposures reported to Texas poison control centers during 2002-2004.

Aripiprazole is an oral atypical antipsychotic drug used in the treatment of schizophrenia and potentially other behavior disorders. The purpose of this study was to describe the epidemiology of aripiprazole exposures reported to Texas poison control centers. Human aripiprazole exposures reported to six Texas poison control centers were identified and comparisons were made between isolated and nonisolated cases with respect to various demographic and clinical factors. Of 280 human exposures involving aripiprazole, 35% were isolated and 65% were nonisolated. The patients were female in 52% of isolated and 60% of nonisolated cases. Isolated cases were significantly more likely to involve children < 6 yr of age. Fifty-eight percent of isolated cases were unintentional while 68% of nonisolated cases were intentional. Nonisolated cases were much more likely to already be at or en route to a health care facility when the poison control center was contacted. Of those cases with a known medical outcome, no adverse clinical effect was reported in 52% of isolated cases and 35% of nonisolated cases. The adverse clinical effects associated with isolated aripiprazole exposures were mainly neurological, cardiovascular, and gastrointestinal, with the most frequently reported adverse clinical effect being drowsiness or lethargy. The most commonly reported treatments for isolated aripiprazole exposures were single dose of activated charcoal, cathartic, intravenous fluids, dilution, lavage, and antihistamines. In conclusion, isolated and nonisolated aripiprazole exposures varied with respect to patient age, exposure reason, management site, and clinical outcome.

Antipsychotic poisoning in young children: a systematic review.

The aim of this review was to determine the spectrum and severity of effects of unintentional antipsychotic poisoning in children. A computerised literature search of MEDLINE (1966 to February 2005) and EMBASE (1980 to February 2005) was undertaken. The Internet was searched using URL: www.google.com. The proceedings of the North American Congress of Clinical Toxicology (NACCT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) were hand searched. All cases of unintentional antipsychotic (all classes) poisoning in children aged 0-6 years were included. The data extracted included the age, weight, antipsychotic, dose, clinical effects, treatment and outcomes. The toxic dose was estimated as the lowest dose causing objective adverse effects.Sixty-eight reports were identified. Few contained all of the required information. Most of the case series included multiple antipsychotics with limited information on individual drugs or all ages with limited paediatric information. For most antipsychotics the ingestion of one tablet caused symptoms that were sometimes severe and usually lasted from 1 to 3 days. Extrapyramidal symptoms (EPS) were often delayed for up to 12-24 hours. Chlorpromazine caused CNS depression, hypotension and miosis; EPS and cardiac effects were rare, and the toxic dose was estimated to be 15 mg/kg. Haloperidol caused drowsiness (rarely coma) and over one-half of patients had neuromuscular effects (mainly EPS), with a toxic dose estimated at 0.15 mg/kg. Thioridazine caused CNS depression and potentially cardiac effects, with a toxic dose of 1.4 mg/kg. Atypical antipsychotics caused significant CNS depression (except risperidone); EPS were less common. Toxic doses were clozapine 2.5 mg/kg, olanzapine 0.5 mg/kg and aripiprazole 3 mg/kg. EPS responded to anticholinergic drug treatment. In summary, unintentional antipsychotic ingestion in children can cause severe effects that last 1-3 days, often with one tablet. Children potentially ingesting a toxic dose or who are symptomatic should be considered for assessment in hospital. Most cases resolve with good supportive care. Toxic doses are only estimates that are based on limited data and should be used with caution until prospective studies are undertaken.

Atypical experience: a case series of pediatric aripiprazole exposures.

BACKGROUND: Aripiprazole is a new psychotropic agent that possesses a unique pharmacologic profile. The drug demonstrates mixed dopamine and serotonin agonist-antagonist activity and has been labeled a third-generation antipsychotic and dopamine-serotonin system stabilizer. Overdose experience is limited, especially in pediatrics. CASE SERIES: Of five pediatric cases identified, toxicity was mainly evident in younger patients. A 2-year-old who ingested 40 mg experienced vomiting and significant lethargy lasting approximately 30 h. A 6-year-old who received two doses of aripiprazole therapeutically experienced lethargy, drooling, and flaccid facial muscles which improved with diphenhydramine. Two adolescents remained asymptomatic despite doses of 120 mg and 300 mg while a third adolescent with an unknown dose experienced transient lethargy. CONCLUSION: Aripiprazole is capable of producing marked lethargy and gastrointestinal upset in pediatric patients. Adolescents in this series experienced only minor, if any, clinical effects. Major clinical effects, i.e., seizures, dysrhythmias, were not reported in this series.

Aripiprazole (abilify) overdose in a child.

Aripiprazole, 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl] butyloxy}-3,4-dihydro-2(1H)-quinolinone, is an atypical antipsychotic medication inaugurating the newest class of atypical antipsychotics: the partial dopamine agonists. It has a particularly long half-life of elimination and variable metabolism secondary to genetic polymorphism. We report an unintentional overdose of 195 mg (17.1 mg/kg) of aripiprazole in a 2.5 year-old child. This patient exhibited CNS depression not requiring respiratory support and without significant cardiovascular effects. CNS effects persisted for almost 2 weeks postingestion.

Overdose of aripiprazole, a new type of antipsychotic.

Aripiprazole is the first member of a new class of antipsychotic medications. Unlike other antipsychotics, it acts as a partial agonist at dopamine D(2) and 5-HT(1A) receptors, thereby mitigating most of the adverse reactions such as extrapyramidal side effects and hyperprolactinemia. Additionally, most research to date has suggested a low incidence of QTc prolongation and orthostatic hypotension at therapeutic doses. Experience in the setting of intentional overdose, however, is limited. We present a case of a 27-year-old woman who intentionally ingested 330 mg of aripiprazole in a suicide attempt. Clinical effects were limited to mild sedation. Serum levels performed by the drug's manufacturer confirmed a total level (parent drug and active metabolite) of 716 ng/mL, nearly six times the upper limit of accepted therapeutic levels. This suggests that aripiprazole's therapeutic index is quite high and reinforces the drug's known safety profile.

Interaction of the putative essential nutrient pyrroloquinoline quinone with the N-methyl-D-aspartate receptor redox modulatory site.

The putative essential nutrient pyrroloquinoline quinone (PQQ) can efficiently mediate reduction and oxidation reactions in a variety of systems. Therefore, we investigated whether this compound could alter the function of the NMDA receptor via a recently described redox modulatory site. In rat cortical neurons in vitro, 50 microM PQQ could reverse the enhancement of 30 microM NMDA-induced whole-cell ionic currents produced by the reducing agent dithiothreitol (DTT; 2-4 mM). PQQ also depressed native responses in a DTT-reversible fashion. In addition, 50-200 microM PQQ produced a significant degree of neuroprotection in an acute model of NMDA-mediated neurotoxicity in astrocyte-rich cultures of rat cerebral cortex. Under certain conditions, PQQ can lead to the formation of oxygen-derived free radicals, and we have previously observed that these reactive species can oxidize the NMDA receptor. Nevertheless, the enzymatic free radical scavengers superoxide dismutase and catalase (10 micrograms/ml each) did not abolish the actions of PQQ. This observation held true even in astrocyte-poor cortical cultures, where neuronal processes are directly exposed to the extracellular milieu. Therefore, under in vitro conditions in which PQQ is presented without an exogenous electron donor, it appears as if the entire neuroprotective effect of PQQ is attributable to a direct oxidation of the NMDA receptor redox site. These results suggest the possibility of a novel role for PQQ, PQQ-like substances, and quinone-containing proteins in the brain, and may represent a novel therapeutic approach for the amelioration of NMDA receptor-mediated neurotoxic injury.