Clinical outcome following 3,4-methylenedioxymethamphetamine (MDMA) intake ranges from mild entactogenic effects to a life-threatening intoxication. Despite ongoing research, the clinically most relevant mechanisms causing acute MDMA-induced adverse effects remain largely unclear. This complicates the triage and treatment of MDMA users needing medical care. The user’s genetic profile and interactions resulting from polydrug use are key factors that modulate the individual response to MDMA and influence MDMA pharmacokinetics and dynamics, and thus clinical outcome. Polymorphisms in CYP2D6, resulting in poor metabolism status, as well as co-exposure of MDMA with specific substances (e.g. selective serotonin reuptake inhibitors (SSRIs)) can increase MDMA plasma levels, but can also decrease the formation of toxic metabolites and subsequent cellular damage. While pre-exposure to e.g. SSRIs can increase MDMA plasma levels, clinical effects (e.g. blood pressure, heart rate, body temperature) can be reduced, possibly due to a pharmacodynamic interaction at the serotonin reuptake transporter (SERT). Pretreatment with inhibitors of the dopamine or norepinephrine reuptake transporter (DAT or NET), 5-HT2A or α-β adrenergic receptor antagonists or antipsychotics prior to MDMA exposure can also decrease one or more MDMA-induced physiological and/or subjective effects. Carvedilol, ketanserin and haloperidol can reduce multiple MDMA-induced clinical and neurotoxic effects. Thus besides supportive care, i.e. sedation using benzodiazepines, intravenous hydration, aggressive cooling and correction of electrolytes, it is worthwhile to investigate the usefulness of carvedilol, ketanserin and haloperidol in the treatment of MDMA-intoxicated patients.
The COVID-19 pandemic has been associated with a decline in mental health of adolescents. The aim of this study was to analyze the rate of deliberate self-poisonings (DSPs) among adolescents reported to the Dutch Poisons Information Center before and during the COVID-19 pandemic. A retrospective study from 2016 until 2021 was performed to characterize DSPs among adolescents, and to analyze trends in the number of DSPs. All DSPs among adolescents with the age of 13 up to and including 17 years were included. DSP characteristics included: age, gender, bodyweight, used substance, dose, and treatment advice. Trends in the number of DSPs were analyzed using time series decomposition and Seasonal Autoregressive Integrated Moving Average models. Six thousand nine hundred fifteen DSPs in adolescents were recorded from January first 2016 until December 31st 2021. Females were involved in 84% of adolescent DSPs. A strong increase in the number of DSPs was observed in 2021 (45% increase compared to 2020), which deviated from the predicted trend based on previous years. This increase was most prominent in 13-, 14-, and 15-year-old female adolescents. Commonly involved drugs were paracetamol, ibuprofen, methylphenidate, fluoxetine, and quetiapine. The contribution of paracetamol rose from 33% in 2019 to 40% in 2021. The strong increase in the number of DSPs during the second year of the COVID-19 pandemic suggests that long-term containment measures such as quarantines, lockdowns, and school closures may enhance self-harm behavior among adolescents, especially among younger females (13–15 years of age), with a preference for paracetamol as DSP substance.
8 October 2021 in British Journal of Clinical Pharmacology
Context: Pregabalin poisoning is mostly benign, although coma and convulsions occasionally occur.Aim: To determine the dose‐toxicity relationship of pregabalin.Methods: Dose‐toxicity data of isolated pregabalin poisonings were collected from (1) a prospective study performed by the Dutch Poisons Information Centre (4 April 2014 to 4 October 2016) and from (2) case reports and case series reported in literature. Poisonings were graded using the Poisoning Severity Score (PSS) and the relationship between dose (mg kg−1) and PSS was evaluated.Results: In our study (n = 21 patients), the most commonly observed symptoms were drowsiness (62%), confusion (29%) and apathy (24%). PSS was none in three (14%), minor in 15 (71%), and moderate in three patients (14%). Most case series also reported a PSS of none to minor in the majority of poisonings (69‐100%). For 34 individual patients (21 from our study and 13 from literature), detailed data on dose and clinical course were available to examine the dose‐toxicity relationship.The median dose was significantly lower in the PSS none‐minor group (“benign”) (8.6 mg kg−1, interquartile range (IQ25‐75) 5.0‐17.6 mg kg−1) than in the PSS moderate‐severe group (“significant toxicity”) (46.7 mg kg−1, IQ25‐75 21.3‐64.3 mg kg−1); estimate of the median difference = 27.3 mg kg−1 (95% confidence interval (CI): 10‐48.6).Conclusions: In general, higher pregabalin doses result in more severe poisonings. Below 20 mg kg−1 the majority of patients (83%) only suffer from mild poisoning. However, large interindividual differences exist in pregabalin‐induced toxicity. Therefore, pre‐hospital triage should not only include pregabalin dose, but also underlying illnesses, co‐exposures and reported symptoms.
Introduction: The annual number of patients > 65 years old about whom the Dutch Poisons Information Center (DPIC) was consulted has more than doubled in the last decade. We aimed to gain insight in the type and circumstances of exposures reported to the DPIC involving older patients, in order to help prevent future poisonings. Methods: Enquiries to the DPIC involving patients > 65 years old were prospectively included from January 2019 to June 2019. Data were collected on patient characteristics (e.g., age, gender, and living situation) and exposure characteristics (e.g., type and exposure scenario). Results: In the first half of 2019, the DPIC was consulted about 1051 patients > 65 years old. The median age of the patients was 77 years old (range: 66–104 years) and women were over-represented (61%). A total of 1650 different substances were reported, 1213 pharmaceutical exposures (74%) and 437 non-pharmaceutical exposures (26%), mostly household products (n = 162). Most pharmaceutical exposures involved cardiovascular agents (n = 367, 30%), central and peripheral nervous system agents (n = 354, 29%), and analgesics (n = 152, 13%). In 71% of the patients exposed to pharmaceuticals, the drugs were taken unintentionally (n = 471), frequently caused by medication errors made by the patients themselves (n = 357, 76%). Most common scenarios included inadvertently taken/given a double (n = 140, 30%) or more than double (n = 94, 20%) dose or the wrong medication (n = 124, 26%). The most common scenario for unintentional exposure to non-pharmaceuticals was “mistook product for food/drink” (n = 122, 37%). Conclusions: The majority of intoxications in older adults are accidental and often involve medication errors. Unintentional poisoning is often preventable. If patients are cognitively impaired, potentially harmful substances should be kept out of their reach and medication should only be administered under direct supervision. Clear labelling, simplified drug regimens and the use of automatic medication dispensers could reduce the risk of medication errors in older patients.
In the past decade, the number of deliberate self-poisonings involving young people has increased strongly worldwide. This study aimed to gain insight into risk factors associated with deliberate self-poisonings among children and adolescents reported to the Dutch Poisons Information Center. A study was performed between 1 February 2022 and 31 January 2023 involving those aged 8-17 years of age with deliberate self-poisoning. Data were collected on patient characteristics (age, gender, body mass index and living situation) and exposure characteristics (type of toxicant, way of acquiring toxicant and day of exposure). The Dutch Poisons Information Center was consulted about 1,424 deliberate self-poisonings among children and adolescents (10-17 years old). A high percentage of patients were female (85 percent), had a body mass index classified as overweight/obese (27 percent) and lived in a mental healthcare facility (13 percent). Patients mainly exposed themselves to pharmaceuticals, especially over-the-counter medications such as paracetamol (46 percent) and ibuprofen (15 percent). Young people living with parents/caregivers had higher odds of ingesting prescription pharmaceuticals or over-the-counter medication, while those living in a mental healthcare facility were more likely to ingest household products, personal care products or foreign bodies (predominantly batteries). This study sheds light on the pervasive issue of deliberate self-poisoning among children and adolescents, advocating for poisoning prevention strategies and promoting mental health of youth. Limitations include reliance on self-reported data from patients and the absence of clinical outcome data. Female gender, a high body mass index and living in a mental healthcare facility are associated with in increased risk of deliberate self-poisonings in children and adolescents (10-17 years old). Prevention of deliberate self-poisonings among youth could focus on restricting access to medication and other potentially hazardous non-pharmaceuticals, such as household products and batteries, as well as limiting the sales of over-the-counter medication, especially paracetamol, to this young population.
5 January 2023 in British Journal of Clinical Pharmacology