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Review

Uncovering the Hidden Burden of Pharmaceutical Poisoning in High-Income and Low-Middle-Income Countries: A Scoping Review

1
Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow G4 0RE, UK
2
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Penang, Malaysia
3
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia
*
Author to whom correspondence should be addressed.
Pharmacy 2023, 11(6), 184; https://doi.org/10.3390/pharmacy11060184
Submission received: 7 September 2023 / Revised: 28 October 2023 / Accepted: 21 November 2023 / Published: 24 November 2023
(This article belongs to the Special Issue Pharmacy Reviews in 2022)

Abstract

:
Pharmaceutical poisoning is a significant global public health concern, causing approximately 190,000 deaths annually. This scoping review aims to comprehensively map the available literature on pharmaceutical poisoning and compare patterns between high-income countries (HICs) and low-middle-income countries (LMICs). A systematic search was performed across the following databases: Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and CINAHL. Studies included were from 1 January 2011 to 31 December 2020, in English, with full text available. Seventy-nine articles were included in the study; 21 were from LMICs and 58 were from HICs. Toxic exposure was largely intentional (77%) in LMICs and accidental (68%) in HICs. Drugs acting on the nervous system were responsible for 95% of toxicities worldwide with analgesics accounting for the largest subtherapeutic group in both LMICs (40%) and HICs (58%). Notable statistics were that HICs accounted for 99% of opioid overdoses, and LMICs accounted for 19% of anti-epileptic-induced toxicities. Overall, the medical outcomes due to poisonings were generally worse in LMICs. The review provides possible interventions to target specific geographic locations, based on the trends identified, to reduce the burden worldwide. Many gaps within the literature were recognised, calling for more robust analytical research.

1. Introduction

Toxic exposure to medicines remains a significant, under-recognised global public health concern. The World Drug Report estimates that pharmaceutical poisoning causes 190,000 fatalities annually [1]; with non-fatal poisoning 20–30 times more prevalent and often causing long-term morbidities [2]. The most prevalent long-term conditions are respiratory, renal or hepatic failure, cognitive impairment, and hypoxic brain injury, depending on the drug(s) involved [3]. This severely reduces patients’ quality of life and puts a strain on healthcare services and society worldwide.
Drug-induced toxicities require immediate action by emergency medicine and national toxicology centres. This creates immense pressure on healthcare systems, apparent from observing hospital admissions alone. In the United Kingdom (UK), approximately 100,000 patients present to emergency departments annually due to drug poisoning, which in turn is responsible for 10% of general ward admissions [4]. Likewise, almost 75% of drug overdose cases in Japan require ambulance services, which account for 15% of intensive care unit (ICU) admissions [5]. Similar trends have been observed worldwide highlighting the burden on emergency services, consuming valuable resources and delaying care for other life-threatening emergencies [5].
Pharmaceutical poisoning can be categorised as intentional (deliberate) or unintentional (accidental). The latter ranks fifth in European injury-related mortality, with the highest rates in Lithuania, Ireland, Estonia, Romania and Latvia [6]. Most unintentional drug poisoning cases occur in children under five, from having a natural curiosity to explore unfamiliar objects and failing to recognise the associated dangers due to their developing cognitive function [7]. Such incidents are most common within a household setting where 10–20% of child exposures are due to their grandparent’s medicines being easily accessible [8]. Many co-morbidities in the elderly require multiple medications, which accumulate in homes [9]. Patients often self-manage their medicines using blister packs, removing the drugs from their original, child-resistant, packaging—consequently increasing the risk of accidental consumption and overdose [10]. Therapeutic errors can also cause unintentional toxicity as well accidental consumption. Such errors are often caused by dosing errors, especially for high-risk medications with a narrow therapeutic index [6].
Alarmingly, most drug toxicity cases are due to intentional self-harm. These intentional exposures occur in countries worldwide regardless of income status, often due to distressing life events, poverty, and psychiatric illnesses, with the highest rates among adults aged 33–44 [11,12]. In 2016, over one billion people worldwide were diagnosed with a mental health condition, 20% of whom were children or adolescents [13,14]. Many of these patients are prescribed drugs to help manage their conditions, highlighting the magnitude of the population’s vulnerability and exposure to medicines with potential toxicities. Over 60% of drug poisoning suicides in Asia are from people with psychiatric conditions, highlighting the correlation between mental illness and pharmaceutical poisoning [1,15,16]. Furthermore, overdosing with prescribed and over-the-counter medicines accounts for 79% of UK emergency department presentations due to self-harm [3,16,17].
Opioids are the major cause of drug-induced toxicity globally [18]. In the Global Burden of Disease Study 2017, 109,500 people died from opioid usage, including prescription, synthetic, and illegal opioids [17,19]. Due to relaxed drug classification and illicit marketplaces availability, the USA has an opioid pandemic. Indeed, over the past 20 years, the USA opioid pandemic has quadrupled in mortality [20]. Similarly, opioids are the main driver of fatal overdoses in Europe, responsible for approximately eight out of 10 drug-induced deaths [21]. The UK and Germany, in particular, account for almost half (47%) of all opioid overdose mortalities in Europe [22].
Socioeconomic marginalisation and cultural differences affect pharmaceutical poisoning regionally. In high-income countries (HICs), medicines are responsible for over 50% of all poisonings [23]. In contrast, in low-middle-income countries (LMICs) such as Ethiopia, India, and Sri Lanka, household products, organophosphates, and pesticides are the major contributors to poisonings, with pharmaceuticals accounting for as little as 10% of toxicities [24]. Because a substantial portion of the population in these places rely on agriculture for money or work, such products are readily available and commonly misused [25,26]. However, drug-overdose mortality is still estimated to be four times higher in LMICs compared to HICs [27]. These inconsistencies are caused by differences in global medicine regulation authority. The lack of regulatory bodies in many LMICs leads to poor access to quality medicines, a higher risk of exposure to falsified drugs, poor prescribing policies, and lenient laws surrounding over-the-counter medicines, where 60% of drugs in developing countries are prescribed or sold inappropriately [28,29,30], contributing to global drug-poisoning disparities.
While extensive literature has been published on pharmaceutical poisoning in specific countries, no efforts have been made to collate this data and analyse trends globally. This would provide an overall evaluation of the key themes of pharmaceutical poisoning and highlight the impact of a country’s income level on such patterns.
This scoping review aims to identify the available literature and compare the patterns of pharmaceutical poisoning between LMICs and HICs, specifically focusing on the reason(s) for exposure, the drug(s) responsible, and the medical outcome(s). All drug poisoning cases are avoidable, so understanding patterns can assist in developing preventative strategies and prioritising geographical areas most in need to target such campaigns.

2. Materials and Methods

This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) (Supplementary Table S1) [31].

2.1. Data Sources and Search Strategy

A comprehensive, systematic search was completed using five electronic databases: Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and CINAHL. In order to form the search strategy, the study objectives were translated into search terms to ensure all relevant articles were captured. This was achieved by completing an initial search on PubMed to identify relevant papers on the topic. Papers were analysed for keywords used in the title and abstract to describe the subject area. The keywords identified formed the search strategy that was used to search the five databases, available in Appendix A. The terms were a combination of words to describe ‘poisoning’ and ‘pharmaceuticals’ as displayed in Table 1. The search results were restricted to articles published from 1 January 2011 to 31 December 2020. In 1997, the World Health Organization (WHO) issued recommendations for poison control. The guidelines highlighted the importance of standardizing poisoning diagnostic and treatment data collection, toxicovigilance, and poison prevention initiatives [32]. The revised version of ‘Guidelines for Establishing a Poison Centre’ followed in early 2021 [33]. We analyzed a decade-long trend using a 2011–2020 criterion prior to the publication of the updated version. A further manual search on Google Scholar was completed to identify any grey literature.
Search results were imported into Endnote 20 (Thomson Reuters, New York, NY, USA) where they were grouped according to the database they were sourced from. Each group was then uploaded to Covidence for screening where duplicates of articles were removed. Two reviewers (CC and AL) independently screened all titles and abstracts of the remaining articles. Bibliographies of relevant studies were also checked for additional publications. Full-texts of potentially relevant studies were then reviewed independently by both reviewers to confirm eligibility according to the inclusion and exclusion criteria. Any discrepancies were discussed between both reviewers, and if a consensus could not be reached, the lead researcher (SAJ) was consulted.

2.2. Study Selection

Studies were included if they fulfilled the following criteria: (1) the study reported on poisoning due to pharmaceuticals; (2) the published date was between 1 January 2011–31 December 2020; (3) full texts and abstracts were available in English; (4) the country where the study was conducted was stated; and (5) the article stated both the reason(s) (e.g., accidental or intentional) and outcome(s) (e.g., length of hospital stay, morbidity or mortality) of the poisoning. Studies were excluded from this review if: (1) they reported on poisoning due to toxins other than medicines (e.g., household products, pesticides etc.) or there was no separation of results between different toxins; and (2) they reported on illicit drug poisoning or did not separate results between medicinal drugs and illicit substances. Reviews, systemic reviews, scoping reviews, meta-analyses, in vitro and in vivo studies, animal studies, conference abstracts or proceedings, reports, letters to the editor, and comments were also excluded.

2.3. Data Extraction and Synthesis

A data-charting form was developed to capsulate the variables required to be extracted from the included studies. This was trialed on five articles to ensure the relevant data was easily charted and the form was altered accordingly. The following data were extracted and tabulated from included studies: (1) author and year of publication; (2) study design and objectives; (3) location of the study; (4) sample size; (5) demographic characteristics including age and gender; (6) reason for exposure; (7) drug(s) responsible for toxicity; and (8) patient-related outcome(s) of poisoning. Extracted information from studies were grouped according to the income status of the country where the study was conducted. Income status was categorised into ‘LMIC’ and ‘HIC’ with reference to the World Bank Country Classifications by Income Level 2021–2022, defined by gross national income per capita [34].
In order to aid identification of the common drug classifications responsible for the poisoning, the Anatomic Therapeutic Chemical (ATC) and Defined Daily Dose (DDD) (ATC/DDD) Toolkit was used to classify drugs into the organ or biological system they target [35]. Some publications present the outcome of the drug poisoning according to the Poisoning Severity Score (PSS), which ranks the severity of the toxicity. The system scores poison outcomes as (0) no effect (patient is asymptomatic); (1) minor effect (mild symptoms); (2) moderate effect (prolonged symptoms); (3) severe (life-threatening symptoms with significant residual disability or disfigurement), or (4) fatal [36]. Finally, age categories were defined and categorised using the WHO definition, which states that a child is under the age of 18 and an adult is 18 years or over. These categories were used when analysing patient demographic trends and the effect of age on pharmaceutical poisoning [37]. Key patterns identified from the extracted data were summarised narratively with the aid of tables and charts into key categories.

3. Results

3.1. Characteristics of Included Studies

The initial search identified 135,936 publications, with four additional studies identified during a manual search on Google Scholar. After screening titles and abstracts, 1359 studies met the inclusion criteria. Full texts of the 1359 studies were assessed for eligibility, where a further 1280 were excluded for the following reasons: wrong study design (n = 796), no separation of results between pharmaceutical drugs and illicit substances (n = 239), no separation of results between pharmaceutical poison and other types of poisoning (n = 111), no full-text available (n = 62), and the study failed to state the reason(s) for poisoning (n = 50) or outcome(s) (n = 22). This resulted in 79 studies being included in the data synthesis of this scoping review, as summarised in the PRISMA-ScR diagram (Figure 1).
Of the included studies, eight were prospective studies: one survey, five cross-sectional studies, one cohort study, and one observational follow-up. The remaining 71 were retrospective studies: 63 cohort and eight cross-sectional studies. Tables presenting a summary of the study characteristics included in this review can be found in Table A1 and Table A2 in Appendix B.

3.2. Overview

The collective sample size of participants was 1,660,165 (HICs: 1,653,519; LMICs: 6646), with ages ranging from one month old to 100 years old. Of the total study group where gender was stated, 51.1% were female (n = 694,234). Twenty-one of the studies (27%) were conducted in LMICs: one each in Algeria, Argentina, Jordan, Morocco, Romania, South Africa, and Sri Lanka; two in India, three in Turkey, and nine in Iran. Fifty-eight studies (73%) were conducted in HICs: 27 in the USA, four in Switzerland, three each in Canada, France, and Denmark; two each in Australia, Israel, Japan, Poland, Finland, and Saudi Arabia, and one study each in the Czech Republic, Republic of Ireland, New Zealand, Singapore, Taiwan, and the UK (Table 2).

3.3. Trends

The results of the scoping review are presented in three broad categories: (i) the reason behind the exposure to drug poisoning, (ii) the pharmaceutical agent responsible for toxicity, and (iii) the medical outcomes of poisonings.

3.3.1. Reason behind Toxic Exposure

The reason for poisoning was classified into two broad categories: intentional or unintentional (accidental). Of the overall sample size, 95% (n = 1,577,159) stated the known reason for being exposed to the drugs at toxic levels with the remaining 5% unknown. For studies that were set in LMICs, 76.2% of exposures were intentional (n = 4809). Further reasons for intentional poisoning were stated for 67% (n = 3216), with attempted suicide accounting for 91.8% (n = 2952), self-harm for 5.3% (n = 172), relationship conflicts noted for 2.2% (n = 72) and homicide for 0.6% (n = 20). For the 23.8% (n = 1503) of patients that were exposed to drug poisoning accidently, detailed reasons were given for 15% (n = 232) and included 31.5% due to careless storage (n = 72), 18.1% due to parental mistakes (n = 42), 18.5% due to therapeutic errors (n = 43), and 31.9% due to ingestion by children while playing (n = 74).
In HICs, 31.7% (n = 499,332) of exposures were intentional. Additional explanations for intentional exposure were given for 5% (n = 25,828); with 92.3% stating attempted suicide (n = 23,829), 6.8% as misuse (n = 1763) and the remaining 0.9% stating abuse of the drug (n = 236). Unintentional poisoning was reported in 68.3% (n = 1,075,873) of cases. Further explanations for accidental exposures included 94.7% as therapeutic errors (n = 508,402), 1.3% as adverse drug reactions (n = 6847), and 4% due to one or more products containing the same active ingredient being consumed (n = 21,361). (Figure 2).
A common trend seen over the included studies was that the intent behind the pharmaceutical poisoning varied depending on age. Fifteen of the studies reported on pharmaceutical poisoning in children, of which 70.2% were exposed accidently (n = 76,398) [42,49,61,67,75,76,78,82,86,91,92,94,95,96,97]. Five studies had separated results for adult exposure where 80.9% of exposures were intentional (n = 725) [73,78,94,96,98].

3.3.2. Types of Pharmaceuticals Responsible for Poisoning

Using the Anatomical Therapeutic Chemical (ATC) Classification toolkit via the WHO, causative drugs responsible for poisoning were divided into the 1st level classification, which has 14 main anatomical or pharmacological groups (Table 3). Of the studies that specifically mentioned the drug(s) responsible for the poisoning, 94.7% (n = 1,368,876) were pharmaceuticals categorised under ‘Nervous System’: 54% (n = 3069) and 95% (n = 1,365,780) in LMICs and HICs respectively.
Looking more closely at the ‘Nervous System’ identified the therapeutic subgroups most commonly responsible (Table 4). In LMICs, 40% (n = 1236) of the central nervous system (CNS)-acting medicines exposed were analgesics, of which 39% were paracetamol, and 31% were from exposure to prescription opioids. In HICs, analgesics accounted for close to 60% of drugs acting on the nervous system, of which 73% (n = 567,925) were prescription opioids and 25% (n = 198,282) paracetamol. Psychoanaleptics (antidepressants, psychostimulants, and anti-dementia drugs) accounted for more than 30% (n = 461,019) of CNS agents. When looking at the global exposures to nervous system agents, LMICs were responsible for less than 1% of toxicities from analgesics, psycholeptics, and psychoanaleptics; 4% of drugs used in opioid dependence, and 19% of toxicities due to antiepileptics.

3.3.3. Outcome of Pharmaceutical Poisoning

Of those hospitalised, 85% were in LMICs (n = 5668) and 20% in HICs (n = 327,439). Across all studies, the average time hospitalised varied from 17.1 h to 13.9 days ranging from 5 h to 91 days [38,54,73]. Less than 1% (n = 11,237) were admitted to the ICU due to poison exposure, where admissions accounted for 10% of the LMIC population outcomes (n = 666) and less than 1% of HIC outcomes (n = 10,571). The most common medical outcomes were all observed in less than 1% of the total study size and included acute kidney injury (n = 9126), organ failure (n = 2765), coma (n = 6776), respiratory depression (n = 6839) and seizures (n = 418).
Nine out of the 79 studies utilised the PSS as a measure of medical outcome [46,50,87,95,96,97,99,100,101]. One was set in Jordan (LMIC) and the remaining eight reported on outcomes from HICs. In the Jordan study, 40% were asymptomatic (n = 363), 39% had mild symptoms (n = 355), 17% were moderate (n = 150) and 4% severe (n = 32). For those reporting using the PSS in HICs (n = 285,481), 56% were asymptomatic (n = 161,269), 32% experienced minor symptoms (n = 90,819), 11% had moderate effects (n = 30,035), 1% were severe (n = 3075) and less than 1% of the poisonings were classified as fatal (n = 283).
Overall, 20,314 deaths were recorded across all included studies. In LMICs, 2% of the pharmaceutical poisoning outcome was death (n = 137), while in HIC 1.2% deaths (n = 20,177) were reported. A key trend observed was the exposure to toxic levels of CNS-acting drugs causing mortality. Eight articles reported deaths as the sole outcome of drug poisoning. Over the eight articles, the collative sample size was 16,175. The five major drug groups responsible for mortality were opioids (47%), anxiolytics (14%), antidepressants (12%), anti-epileptics (5%) and methadone for opioid substitution therapy (4%) [58,60,65,70,89,90,102,103].

4. Discussion

After synthesising the data from the 79 papers that met the inclusion criteria, specific trends between economically developed and developing countries were identified, and research gaps were recognised.

4.1. Reason behind Toxic Exposure

The disparity in reasons for pharmaceutical poisoning between LMICs and HICs was remarkable. Over 75% of LMICs’ exposures were deliberate self-poisonings, with 92% further stating overdose with the intent of suicide. Previous literature has recognised the gravity of the issue in the developing world, with eight of the top ten countries with the highest suicide rates being LMICs [104]. In contrast, accidental exposure to pharmaceuticals accounted for 68% of toxicities in HICs, with over 94% of these due to therapeutic errors, including administration errors, consuming multiple medicines with the same active ingredient, adverse drug reactions, and poor storage leading to child exposure. This finding may be due to more efficient error reporting and surveillance systems in developed countries [105].
With regard to the effect of age on poisoning, the results reaffirmed that child toxicities are predominantly unintentional, with adults mostly intentional in both LMICs and HICs [7]. The disparity in the causes of pharmaceutical poisoning between LMIC and HIC is likely attributable to a number of socioeconomic factors, including the availability of healthcare resources, poverty, access to treatment and support services, cultural attitudes towards mental health, and other socioeconomic factors. Higher rates of intentional self-poisoning with suicidal intent in LMICs reflect a lack of access to mental health resources and support, poverty and bad living conditions, or a cultural stigma associated with seeking assistance for mental health difficulties. In contrast, accidental poisonings may be more widespread in HICs due to higher access and availability of pharmaceutical medications, and a lack of knowledge or education regarding their proper use and potential risks [106,107,108].

4.2. Types of Pharmaceuticals Responsible for Poisoning

The overwhelming majority (94.7%) of pharmaceutical toxicities worldwide were from drugs acting on the nervous system, with analgesics accounting for the largest sub-group responsible. Opioids were responsible for most analgesic exposures, with the problem largely residing in HICs, likely due to their accessibility in these areas being far greater than for LMICs, where a considerable lack of pain relief medications is available [109]. Indeed, in a Lancet Commission Report, it was reported that only 0.1 metric tonne of morphine-equivalent opioids are delivered to LMICs, from almost 300 metric tonnes [110]. Furthermore, overprescribing and long-term use of opioids are considered the root cause of toxicities in HICs due to risks of dependence, often leading to misuse and overconsumption [111]. Medicines used in opioid substitution treatment were also commonly responsible for the poisoning, perhaps due to the vulnerability of patients receiving such treatment and the risk of co-ingesting opiates along with substitution therapy.
Findings from this review also revealed that poisoning due to psychoanaleptics accounted for the second largest subtherapeutic group in HICs, while psycholeptics were the second largest in LMICs. Similar results have previously been reported where analgesics, psycholeptics (mostly benzodiazepines), and pschoanaleptics (particularly antidepressants) were the groups largely responsible for intoxication [112]. The results also matched previous findings where toxicity due to a combination of drugs was common in LMICs and HICs due to the risks of drug-drug interactions. Despite these three subgroups accounting for most pharmaceutical toxicities worldwide, LMICs were responsible for less than 1% of these poisonings meaning the problem significantly exists within HICs. However, a subgroup where LMICs were particularly accountable for the global burden was exposure to antiepileptics, where almost 20% of toxicities occurred in these developing countries. Part of the explanation may be that 85% of epileptic patients reside in LMICs [113]. Furthermore, antiepileptics are approved for a number of indications besides the treatment of epilepsy, including neuropathic pain and mood stabilisation, common conditions prevalent in these areas and two major groups vulnerable to intentional overdose and suicide ideation [113,114]. Additionally, access to anticonvulsants is far more attainable than analgesics in these deprived countries, particularly first-generation anticonvulsants, which are notorious for their poor safety profile with a high risk of toxicity in comparison to second-generation agents [113].

4.3. The Outcome of Pharmaceutical Poisoning

Analysing the outcome of drug-related poisoning, findings revealed that 85% and 20% of those exposed were in LMICs and HICs respectively, with the duration of hospital stay ranging from five hours to 91 days. Admissions to the ICU were over 10 times more common in the developing world, and fatality rates from overdose were almost twice as high compared to HICs. This can be explained by the intent affecting the outcome where there is a direct correlation between the dose consumed and a worse prognosis. Thus, mortalities are higher in LMICs as far larger quantities are likely to be consumed when the exposure was intentional. Furthermore, the disparities in healthcare resources are also responsible for poorer outcomes. Access to healthcare resources and poison information centres that advise on the management of poisoning is far scarcer in LMICs, leading to delayed treatment and interventions, increasing the exposure length and ultimately worsening the outcome [115]. For studies in this scoping review that reported according to the PSS, most outcomes were asymptomatic and mild in severity, and very little of the study population suffered from severe (life-threatening) or fatal effects. Therefore, findings reveal that pharmaceutical poisoning is associated with more short-term illnesses and morbidities than mortality.

4.4. Future Research and Recommendations

When considering the geographical location of included studies, an uneven distribution between those conducted in LMICs and HICs was apparent. Despite over 85% of the world’s population residing in LMICs, there was a poor representation of the developing world, with 73% of the studies reporting on HICs [114]. Thus, obtaining an in-depth comparison of poisoning patterns between the economically developed and developing world was difficult. The low number of papers could be due to the exclusion of a large number of papers which did not separate between poisoning due to pharmaceuticals and other types of poisons. However, the lack of poison information centres partly justifies this, a major resource for collecting such data. According to the WHO, only 47% of countries have an established poison centre, with African, Eastern Mediterranean, and Western Pacific regions particularly lacking [116]. Therefore, it should be a public health priority for governments to invest funding into establishing and strengthening these centres. This would not only improve surveillance for future research but also guide managing drug-induced poisons, thus improving outcomes.
Globally, the expenditure on mental health services is inadequate and is disproportionately worse in LMICs compared to HICs, with regard to the magnitude of the problem and the poisonings that arise from it [114]. It is estimated that globally, there is an average of 3.96 psychiatrists per 100,000 people. However, in developing countries such as Ethiopia, India, Nigeria, and Pakistan, those rates are 0.04, 0.301, 0.06, and 0.185, respectively [114]. Furthermore, within countries, there are large variations in access to mental health workers, with the majority often concentrated in urban areas meaning those living rurally have poor access and minimal support available [114]. There is an urgent need to train and employ more individuals in the mental health workforce to increase accessibility to non-pharmacological treatment. This would also limit the prescribing of psycholeptics and psychoanaleptics; two major drug classes highlighted in this scoping review to be responsible for toxicities. Furthermore, setting up referral schemes after patients are discharged from an intentional overdose to provide appropriate support would reduce the likelihood of reoccurrence.
Due to the overwhelming impact of opioids on the burden of pharmaceutical poisoning, it is essential that improvements in national policies are made in the areas where opioid overdose is particularly problematic. There is an urgent need for improved legislation and policies with regard to the prescribing and duration of treatment with opioids as well as improved education on chronic pain management. Furthermore, better recognition of those requiring support from addiction services and increased access to the opioid-reversal agent naloxone would reduce the burden of opioid toxicities [117].
Those most vulnerable to opioid toxicity are often regular patients to pharmacies [118]; thus, having a supply of naloxone in every pharmacy and training staff on recognising the signs of an overdose and the protocol to follow would be immense in the prevention of life-threatening toxicities. That being said, it is important to consider the difficulties of implementing such strategies in both HICs and LMICs. In HICs such as the USA, there are relaxed policies and opioids are easily accessible [119]. While in LMICs, pharmacy services are reported to be lacking, with the drive being profit over patient care [120]. Furthermore, access to medicines is also limited [121], so having naloxone available in every community pharmacy may be logistically difficult. Perhaps having a national initiative scheme available to pharmacies to widen access to services within the community would help improve patient-centred care and reduce toxicities from occurring or refer those who present at risk in a reasonable time.
Many countries have yet to prioritise poisoning prevention strategies despite the severity of the issue. Public health campaigns focusing on increasing parental awareness of storing medicines in their original packaging and keeping them out of sight and reach of children are required to prevent the risk of confusing them for ‘sweets’ [6]. Many intentional poisonings are often impulsive; thus, limiting the accumulation of medicines stored in households by promoting safe disposal via pharmacies would be an effective strategy. Such campaigns could be promoted within healthcare settings and social media should be utilised to target large audiences [122].
Several research gaps were identified whilst conducting this scoping review. As discussed above, data available from LMICs were minimal, underlining the need for more robust analytical studies to reduce the disparity and underrepresentation of the developing world. In addition, research understanding the barriers to establishing poison information centres in LMICs and how these could be addressed would be valuable for enhancing the response to drug-induced toxicity in these regions despite the availability of multiple guidelines for establishing poison centres and other aspects of dealing with poisonings [33,123].
To address the disparity in patterns of pharmaceutical poisoning between LMICs and HICs, a less costly strategy of increasing awareness would be beneficial. This could be achieved by collecting and analysing the attitudes and competencies of healthcare professionals practising outside of hospitals towards managing drug-induced poisonings. This research could identify areas where further education and awareness of resources available, such as tox-based apps, would improve the triaging of patients and reduce unnecessary referrals from community settings to emergency departments.
As well as this, the findings revealed that hospitalisation and utilisation of emergency departments is a common outcome of drug-related poisoning despite many toxicities being asymptomatic or mild in severity. Thus, attempts to collect and analyse the attitudes and competencies of healthcare professionals practising in sectors beyond hospitals in advising and managing drug-induced poisons would be valuable. Additional personnel or qualified emergency physicians and the development of multidisciplinary teams in major hospitals in LMICs are also required to address the issue of pharmaceutical poisoning better. This will ensure that patients in emergency settings receive prompt and effective care and lessen the burden on the healthcare system.
Generative AI technology has the ability to revolutionise how individuals obtain information about poisonings and seek medical care. By providing free and immediate access to information about various types of poisonings, their symptoms, and risk reduction strategies, this technology can assist individuals in determining if they or someone they know has been exposed to a harmful substance, thereby facilitating more targeted and effective treatment. There are limitations to chatbot AI technology despite its potential benefits. Challenges such as the quality and diversity of training data, the limitations of pre-programmed responses, and platform constraints can impact the accuracy and relevancy of the delivered information. It is crucial to use chatbot AI technology to complement professional medical advice, not as a replacement.

4.5. Strengths and Limitations

This scoping review is the first attempt to collate the broad field of literature and identify patterns of pharmaceutical poisoning at a global level. A few limitations were noted. Firstly, only articles that were available in English were included, which likely limited the data available in non-native English-speaking countries. Secondly, a large number of initial studies were found during the search. Despite this ensuring all relevant papers were captured, it perhaps reflects that the search strategy was not specific enough to the study’s aims. We also excluded from the scoping review all categories of reports, ranging from individual institution annual reports to health organization reports, that would have provided a deeper understanding of the trend. However, this will necessitate translation in addition to other difficulties, as not all nations have such reports.
Thirdly, the USA was overrepresented in this review accounting for 47% of HIC studies. Although this highlights the ongoing issues in the USA with the opioid epidemic, it reduces the attempt to analyse trends of pharmaceutical poisoning in HICs in general. In addition, the reported trend may be understated due to the availability of panels of substance analysis in various nations. Despite this, the majority of poisoning cases are treated based on clinical judgment of the information acquired, and drug concentration monitoring is not always used to determine causality. Finally, where articles collected the data from poison databases, this often required voluntary reporting. Self-reported data has the potential risk of bias, thus, the accuracy of poison reports is unknown. Furthermore, data is also compiled from the volume of calls poison centres receive from physicians. However, many physicians are familiar with the diagnosis and management plan for often-occurring toxicities and so do not need to refer to the centres for advice. Thus, the available data is unlikely to comprehensively reflect the magnitude of the problem.

5. Conclusions

This review is the first attempt to analyse the data available on pharmaceutical poisoning worldwide. Findings reveal that most drug toxicities are intentional in LMICs and accidental in HICs. Globally, the problem mostly lies with drugs acting on the nervous system, particularly analgesics, and medical outcomes from poisoning are generally worse in LMICs. Implementation of the suggested recommendations including the establishment of poison information centres worldwide, strengthening mental health resources, tightening medicine regulations, improving healthcare professional awareness surrounding drug toxicity and public health prevention campaigns would make a positive contribution towards alleviating the burden of these preventable injuries. Despite recognising the epidemiological patterns of poisoning, gaps in the literature were recognised calling for more robust analytical research.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/pharmacy11060184/s1, Table S1. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist.

Author Contributions

Conceptualization: S.A.J.; Data curation: C.C. and A.L.; Formal analysis: C.C. and A.L.; Investigation: C.C. and A.L.; Methodology: S.A.J.; Project administration: S.A.J. and B.T.; Supervision: S.A.J. and B.T.; Validation: All authors; Writing—original draft: C.C.; Writing—review and editing: All authors. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Acknowledgments

The authors would like to thank the following experts for reviewing the manuscript and providing valuable feedback, which were used to make significant improvements to the manuscript: Vikneswaran Murugaiyah; Daniel Malone. His areas of expertise include neurophysiology and pharmacology of drugs used for central nervous system disorders; and Tye Sok Cin, Research Fellow with the Section of Genetics and Epidemiology, Joslin Diabetes Center, Harvard Medical School. She specializes in personalized medicine, specifically the prediction of individualized treatment responses.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

ADRAdverse drug reaction
AKIAcute kidney injury
ATCAnatomic Therapeutic Chemical
BBBeta blocker
CCBCalcium channel blocker
CVSCardiovascular
CNSCentral nervous system
DDDDefined Daily Dose
EDEmergency departments
ENTEar, nose, and throat
GIGastrointestinal
HICsHigh-income countries
ICUIntensive care unit
LMICsLow-middle-income countries
MIMyocardial infarction
MALAMetformin associated lactic acidosis
NSAIDNon-steroidal anti-inflammatory
OTCOver the counter
POUPyrexia of unknown origin
PSSPoisoning Severity Score
SSRISelective serotonin reuptake inhibitor
TCATricyclic antidepressant
TBTuberculosis
UKUnited Kingdom
USAUnited States of America

Appendix A. Search Strategy

1.Poison*.mp.
2.toxic.mp.
3.overdose.mp or intoxication/
4.excessive.mp.
5.substance abuse/
6.drug misuse/
7.1 or 2 or 3 or 4 or 5 or 6
8.pharmaceutical.mp.
9.medicine/
10.drug/
11. opioid.mp.
12.8 or 9 or 10 or 11
13.7 and 12
14. limit 13 to (English and yr = 2011–2020)

Appendix B

Table A1. Characteristics and data extracted from included studies set in low-middle income countries.
Table A1. Characteristics and data extracted from included studies set in low-middle income countries.
Author (Year)Study DesignSettingSample SizePatient Demographics (Age (Years) * and Gender a)Reason for ExposureDrug Responsible for Poisoning bOutcome from Exposure c
Ghaemia et al. [42]A prospective cross-sectional study at a tertiary toxicology centre in Northeast IranNortheast Iran126Ages 1–14: 126
Mean age: 2.8
  • M: 69
  • F: 57
Accidental: 126
  • Poor storage: 73
  • Parent mistakes: 14
  • Therapeutic error: 39
  • methadone: 65
  • buprenorphine: 6
  • Other opioids: 55
Symptoms:
  • Drowsiness: 98
  • Apnoea: 35
  • Bradypnea: 47
  • Miosis: 87
  • Convulsions: 11

Hospitalised 126Deaths: 3
Hamedi et al. [49]Cross-sectional study on children admitted to EDb of Imam Reza Hospital. Data was collected from laboratory results and subjective data from parents’ responses.Northeast Iran79(3 months–15 years)
  • M: 45
  • F: 34
Accidental: 74
  • Ingested by child: 42
  • parents’ mistake: 28
  • Therapeutic error: 4

Intentional (suicide attempt): 1Unknown: 4
  • methadone: 79
Hospitalised: 79
  • Average length of stay: 31.77 h (2–87 h)

Deaths: 2 (due to prolonged hypoxia and delay in hospitalisation)
Jabbehdari et al. [43]Descriptive-sectional study on hospital admissions with methadone poisoning at Loghman-Hakim Hospital in the second half of 2012.Iran31Mean age: 4.6
  • M: 16
  • F: 15
Accidental: 31
  • methadone: 31
Hospitalised: 31
  • Respiratory acidosis: 21
  • Leukocytosis: 17
  • Hyponatremia: 5
  • Prolonged QT interval: 7
Bilel et al. [38]A retrospective descriptive study on poisonings received at the Oran University Hospital over 8 years using a pre-established information sheet on patient and circumstances of poisoning along with biological samples.Algeria400
  • 4 m–5: 47
  • 6–15: 48
  • 16–25: 204
  • 26–35: 73
  • >35: 26
(1 month–70 years)
  • M: 100
  • F: 300
Accidental: 72
Intentional (suicide attempts): 328
  • paracetamol: 400
Hospitalised: 400
  • Average time hospitalised: 5 h–7 days
  • Liver injury: 8

Death: 5
Kara et al. [124]Retrospective study comprised records of patients admitted to ED of Konya Numune Hospital between 2009–2011.Turkey932
  • <15: 14
  • 14–24: 617
  • 25–34: 249
  • 35–44: 86
  • 45–54: 14
  • 55–64: 14
  • >65: 22

  • M: 236

  • F: 696
Intentional (suicide attempts): 932
  • Antidepressant or antipsychotic: 162
  • Antiepileptic: 22
  • paracetamol: 71
  • NSAID: 59
  • GI drugs: 27
  • Antibiotic: 24
  • Antianemic: 15
  • Myorelaxant: 11
  • CVS drugs: 17
  • Anti-viral: 9
  • Contraceptive: 6
  • Respiratory drug: 6
  • Antidiabetic: 5
  • Antihistamine: 3
  • Co-ingestion: 249
  • Unknown: 246
Hospitalised: 932
  • Average length of stay: 24 h (24–168 h)

Death: 1
Buffone et al. [39]Descriptive, retrospective study based on the data collected from reviewing the medical records of patients 10–19 years at ED of Municipal Hospital of Bahia Blanca.Argentina72Mean age: 16
(10–19)
  • M: 20
  • F: 52
Intentional: 72
  • Family conflicts
  • School conflicts
  • Couple conflicts
  • Anxiolytics: 22
  • Analgesics: 10
  • Antihypertensives: 2
  • Antihistamines: 3
  • CNS stimulant: 2
  • Antidepressants: 2
  • Antibiotics: 1
  • Unknown: 30
Hospitalised: 72
  • Average length in hospital: 2.5 days
  • Admitted to ICU: 1
Hocaoglu et al. [54]Cross-sectional descriptive study reviewing theophylline exposure cases reported to Dokuz Eylul University Drug and Poison Information Centre (DPIC).Turkey354
  • <18: 146
  • >18: 206

  • M: 85

  • F: 257
  • Unknown: 12
Intentional: 291
Accidental: 46
Unknown: 17
  • theophylline: 354
Hospitalised: 354
  • Average length of stay: 17.1 h

Death: 2
Mehrpour et al. [44]Retrospective cross-sectional review based on hospital records of acute poisonings managed in ICU during a 7-year period in a single center in Birjand, IranIran267
  • 20–35: 167
  • 35–50: 46
  • 50–65: 26
  • >65: 28

  • M: 173

  • F: 94
Accidental: 22
Intentional: 151
  • Suicide attempts: 102
  • Unknown: 49
  • paracetamol: 2
  • Benzodiazepine: 34
  • Antidepressant: 33
  • Antipsychotic: 20
  • Anticonvulsant: 4
  • Betablocker: 6
  • Opioids: 79
  • Co-poisoning: 8
  • Unknown: 81
ICU: 267
Death: 52
Azekour et al. [51]Epidemiological retrospective study reviewing medicinal poisoning registered with the Provincial Delegation of Health in Errachidia between 2004–2016Morocco180Mean age: 21 (2–75)
  • M: 42
  • F: 131
  • Unknown: 7
Accidental: 101
Intentional: 72
Unknown: 7
  • alprazolam: 15
  • carbamazepine: 9
  • chlorpromazine: 9
  • trihexyphenidyl hydrochloride: 6
  • amitriptyline: 6
  • bromazepam: 6
  • lamotrigine: 6
  • paracetamol: 6
  • prazepam: 6
  • valproic acid: 6
  • bromazepam: 3
  • phenobarbital: 3
  • Contraceptives: 9
  • cyproheptadine: 3
Hospitalised: 132
Death: 3
Taheri et al. [125]Descriptive analytical study performed from 2010–2012 in the poisoning emergency and clinical toxicology departments of Noor Hospital affiliated with Isfahan University of Medical Sciences.Iran385Mean age: 32.1 (1–90)
  • M: 294
  • F: 91
Intentional: 222
Accidental: 153
  • methadone: 385
Hospitalised: 385
  • Pulmonary oedema: 3
  • Aspiration pneumonia: 21

Death: 7
Weerasinghe et al. [53]Retrospective analysis of self-harm cases. Data collected from primary and referral hospitals.Sri Lanka54
  • 15–20: 32
  • 21–25: 13
  • >26: 9

  • M: 2

  • F: 52
Intentional: 52
Accidental: 2
  • Contraceptives: 54
Hospitalised: 54
  • Average stay: 24 h
Bagherian Rad et al. [45]Cross sectional retrospective study carried out on all patients referred to Loghman Hakim Hospital from 2011–2016.Iran229Mean age: 24
(13–90)
  • M: 77
  • F: 152
Intentional: 224
Unintentional: 5
  • NSAID: 217
  • Co-ingestion: 12
Hospitalised: 229
ICU: 8
Duration of hospital stay:
  • <12 h: 6
  • 12–24 h: 213
  • 24–48: 7
  • >48: 3

Death: 1
Nagaralu et al. [40]Retrospective review using data from ED at four tertiary care hospitalsIndia708
  • 1–20: 277
  • 21–40: 277
  • 41–60: 125
  • >61: 29

  • M: 407

  • F: 301
Intentional: 484
Accidentall: 149
Homicidal: 20
Unknown: 55
  • NSAID: 161
  • Antiepileptics: 117
  • Antidiabetics: 114
  • CVS drugs: 108
  • Antipsychotics: 78
  • Anxiolytics: 73
  • Anti-thyroids: 57
Hospitalised: 708
Death: 42
Anthony et al. [41]Observational retrospective review using records from a tertiary care hospital over 15 monthsIndia91Mean age: 28.1
  • M: 23
  • F: 68
Intentional: 72
Accidental: 19
  • Sedatives: 19
  • Antiepileptics: 19
  • Unknown: 53
ICU: 61
  • Average length in ICU: 3.94 days

Deaths: 3
Shadnia et al. [46]Retrospective cohort study using data from patients admitted to Loghman Hakim Hospital Poison Centre over 4-month period.Iran100
  • 12–20: 38
  • 21–30: 50
  • 31–40: 8
  • 41–50: 3
  • >50: 1

  • M: 82

  • F: 18
Intentional (suicide attempt): 93
Unknown: 7
  • tramadol: 100
  • Co-ingestion (paracetamol, benzodiazepines, clarithromycin and naltrexone): 15
Hospitalised: 100
  • Seizures: 100
  • Nausea: 13
  • Emesis: 10
  • Recurrent seizures: 7
Yehya et al. [50]Retrospective descriptive study using data from PharmacyOne Poison call centre, 2014–2018Jordan900
  • <5: 306
  • 6–10: 129
  • 11–20: 32
  • 21–50: 365
  • >50: 68

  • M: 473

  • F: 427
Intentional: 236
  • Suicidal: 228
Accidental: 596
  • Medical error: 68
Unknown: 68
  • Analgesics: 252
  • CVS: 76
  • CNS: 63
  • Antihistamines: 94
  • Vitamins and supplements: 15
  • Anti-diabetic: 30
  • Antibiotics: 70
  • Co-ingestion: 125
  • Unknown: 31
PSS
  • No effect: 363
  • Mild effect: 355
  • Moderate: 150
  • Severe effect: 32
Van hoving et al. [11]Retrospective review extracting data from Khayelitsha Hospital Emergency Care databaseSouth Africa192
  • <25: 91
  • 25–35: 65
  • >35: 36

  • M: 60

  • F: 132
Intentional: 192
  • Analgesics: 68
  • CVS: 44
  • Antivirals: 28
  • Antibiotics: 27
  • Vitamins and Minerals: 24
  • Antihistamine: 15
  • Anticholinergic: 11
  • CNS: 11
Hospitalised: 192
  • ED: 154
  • ICU: 14
  • Referred to other hospital: 11

Death: 4
Hashemneiad et al. [47]Cross sectional study using data from patients admitted with drug poisoning at Karaj Shariati Hospital over 1 yearIran172Mean age 29.8
(12–80)
  • M: 86
  • F: 86
Intentional: 172
  • Benzodiazepines: 50
  • Antipsychotic/antidepressant: 30
  • Opioids: 50
  • NSAID: 12
  • Methadone: 6
  • Unknown: 36
Hospitalised: 172
  • Seizures: 22

Death: 10
Yaylaci et al. [55]Retrospective study of patients at follow-up admitted with intoxication to the ICU between 2009–2011Turkey153
  • 17–25: 69
  • 26–35: 51
  • 36–45: 20
  • 46–55: 7
  • >56: 6
  • Mean age: 29.4
  • M: 49
  • F: 104
Intentional (suicide attempt): 144
Accidental: 9
  • Multiple drugs: 47
  • Antidepressant or antipsychotic: 46
  • Analgesics: 20
  • Unknown 29
ICU: 153
Average length of stay: 2.4 days
Khodabandeh et al. [48]Prospective cross-sectional study among acute drug poisoning patients at a single hospital over 1 yearIran410
  • <18: 42
  • 18–24: 102
  • 25–34: 154
  • 35–44: 96
  • >45: 16

  • M: 249

  • F: 161
Accidental: 35
Intentional: 375
  • Suicide attempt: 71
  • Single drug: 222
  • Multiple: 133
  • Benzodiazepine: 103
  • Opioid: 98
  • Unknown: 209
Hospitalised: 410
  • Lung injury: 153
Sorodoc et al. [52]Retrospective review using data from a single tertiary center from Iasi County, RomaniaRomania811
  • 18–20: 132
  • 21–30: 242
  • 31–40: 201
  • 41–50: 104
  • 51–60: 72
  • 61–70: 36
  • >70: 24

  • M: 272

  • F: 539
Accidental: 63
Intentional (Suicide attempt): 748
  • Benzodiazepines: 111
  • Antiepileptics: 101
  • Barbiturates: 69
  • CVS drugs: 48
  • NSAID: 24
  • Antidepressant: 22
  • TB drugs: 15
  • Antibiotics: 11
  • Unknown: 80
  • Antidiabetic: 7
  • Opioids: 5
  • Multiple drugs: 267
  • Unknown: 41
Hospitalised: 811
  • ICU: 162
  • Average length of hospital stays: 3.12 days
  • Referred to psychiatric consultant: 666

Death: 2
* Where available, age ranges are displayed in brackets below the noted age categories and mean age of the sample size. a M:male; F: female. b NSAIDs: non-steroidal anti-inflammatory drugs; GI: Gastrointestinal; CVS: cardiovascular; CNS: central nervous system; TB: Tuberculosis. c ED: emergency departments; ICU: Intensive care unit.
Table A2. General characteristics of included studies set in high-income countries.
Table A2. General characteristics of included studies set in high-income countries.
Author (Year)Study DesignSetting aSample SizePatient Demographics (Age (Years) * and Gender b)Reason for ExposureDrug Responsible for Poisoning cOutcome from Exposure d
Jensen et al. [62]A retrospective nationwide descriptive study using 2 databases; the Danish Poison and Information Centre (DPIC) and the State Serum Institute of Denmark. (SSI)Denmark1505
  • 0–1: 52
  • 2–5: 267
  • 6–12: 54
  • 13–16: 101
  • 17–60: 900
  • >60: 82
  • Unknown: 49

  • M: 554
  • F: 907
  • Unknown: 44
Intentional: 1142
  • Suicide attempt: 514
Accidental: 350
Unknown: 71
  • promethazine: 556
  • cyclizine: 295
  • cetirizine: 232
  • loratadine: 132
Hospitalised: 456
  • Average length of stay: 1 day
  • Max. length of stay: 14 days

Deaths: 14
Martin et al. [86]Retrospective review of all paediatric admission at Eastern Maine Medical Centre (EMMC) from 1999–2009.USA22
  • 1–12: 16
  • 13–17: 6

  • M: 10

  • F: 12
Accidental: 16 (All aged between 1–12)
Intentional: 6 (All aged between 13–17)
Drug source was family or friend for 82% of cases
  • methadone: 10
  • buprenorphine: 12
Hospitalisation: 22
  • Admitted to ward: 6
  • PICU: 16
  • Mean hospital stay: 2.3 days
  • Range of stay: 1–7 days
Gregoriano et al. [94]Retrospective analysis of reports to a National Poison Centre 1995–2013Switzerland40
  • 0–18: 26
  • >18: 14

  • M: 21
  • F: 19
Children:
  • Suicide attempt: 3,
  • Accidental: 11
Adults:
  • Suicide attempt: 22
  • Accidental: 4
Children:
  • azathioprine: 9
  • 6-mercaptopurine: 5
Adults:
  • azathioprine: 26
Hospitalised: 40
  • Average length of stay: 2 days (1–11 days)
Martos et al. [78]An observational study reported to national poison centre between 1995–2013Switzerland75
  • 1–16: 30
  • 17–83: 45

  • M: 24

  • F: 51
Accidental: 22
  • 20 children
  • 3 adults

Intentional: 50
  • 43 adults
8 children older than 12
  • tolperisone: 72
  • tolperisone and NSAIDS: 3
No effect:
  • 6 adults
  • 17 children
Mild effect:
  • 25 adults
  • 10 children
Moderate effect:
  • 9 adults
Severe effects:
  • 5 adults
  • 3 children
Cairns et al. [56]Retrospective observational study. Data collected from NSW poisons information centre 2004–2014Australia 1735Mean age: 17
  • M: 820
  • F: 816
  • Unknown: 99
Intentional: 1735
  • dextroamphetamine: 575
  • methylphenidate: 1059
  • modafinil: 18
  • atomoxetine: 83
Hospitalised: 1594
Referred to toxicologist: 60
Alruwaili et al. [81]Prospective, descriptive cross-sectional study looking at 2 paediatric ED in Riyadh over 2 yearsSaudi Arabia1035
  • <12: 1016
  • >12: 19

  • M: 528

  • F: 394
  • Unknown: 113
Unintentional: 906
Intentional: 22
Unknown: 104
  • Analgesics: 138
  • Anticholinergics: 57
  • CVS drugs: 56
  • Anti-diabetic: 52
  • Supplements: 42
  • Antipsychotics: 39
  • Antimicrobials: 3
  • salbutamol: 17
  • Birth control: 25
Hospitalised: 1035
  • Paediatric ward: 71
  • Paediatric ICU: 71
Eluri et al. [87]Retrospective analysis of errors reported to USA poison control centre from 2000–2012USA533,763
  • 0–5: 196,797
  • 6–19: 101,365
  • 20–49: 119,340
  • over 50: 90,179
  • Mean: 22.3
  • Age unknown: 26,082

  • M: 229,938

  • F: 302,919
  • Unknown: 906
Accidental:
  • Therapeutic error: 484,360
  • >1 product with same ingredient: 21,361
  • Unknown: 28,042
  • paracetamol: 196,797
  • Opioids: 123,613
  • NSAIDs: 13,610
  • No effect: 80,236
  • Minor: 32,571
  • Moderate: 7077
  • Major effect: 1004
  • Death: 145
  • Unknown: 412,730
Ichikura et al. [72]Cohort study from an ICU in Japan from 2006–2013Japan676
  • <19: 38
  • 20–34: 328
  • 35–49: 227
  • 50–64: 47
  • >65: 36

  • M: 156

  • F: 520
Intentional: 676
  • Suicide attempt: 403
  • Benzodiazepine: 537
  • Antidepressants: 421
  • Barbiturates: 155
  • Antipsychotics: 279
  • Analgesics: 135
  • GI drugs: 77
  • Anti-Parkinson: 71
  • Antihistamines: 31
  • CVS drugs: 19
  • Anticonvulsants: 4
  • Other: 116
ICU: 676
Post et al. [88]Retrospective analysis of calls to USA poison control centres (NPDS) from 2007–2016USA 11,275
  • <6: 9709
  • 6–12: 315
  • 13–19: 1251
  • Mean age: 3.8

  • M: 5985

  • F: 5221
  • Unknown: 69
Accidental: 10,053
Intentional: 1001
  • buprenorphine: 11,275
Hospitalised: 8401
Deaths: 11
Kamour et al. [85]Retrospective study using NPIS telephone enquires related to 4 NSAIDs between 2007–2013UK 22,937(14–98)
  • M: 9596
  • F: 13,145
Intentional: 11,104
Drug misuse: 65
Accidental: 9826
Unknown: 602
  • mefenamic acid: 925
  • ibuprofen: 17,302
  • diclofenac: 3385
  • naproxen: 1325
  • CNS toxicity: 322
  • Seizures: 48
  • Confusion: 19
  • Anxiety: 9
  • Reduced consciousness: 163
  • Dizziness: 79
  • Agitation: 28
Tan et al. [83]Retrospective review of paracetamol overdose presenting to a tertiary hospital in Singapore Singapore177Mean age: 25
(21–36)
  • M: 51
  • F: 126
Intentional: 136
Unintentional: 40
Intent unclear: 1
  • paracetamol: 177
Hospitalised: 177
  • Mean length of hospital stay: 3 days (1–28 days)
  • Liver damage: 16
  • Liver failure: 2
Madadi et al. [58]Retrospective study using the Office of the Chief Coroner of Ontario. All deaths coded drug-related were reviewed.Canada1359Mean age: 44
Age range: 16–89
  • M: 867
  • F: 492
Accident: 924
Unknown: 221
Suicide: 214
  • Opioids: 1149
  • methadone: 210
Death: 1359
Austin et al. [89]Population based study using North Carolina death certificate data to identify drug overdose decedentsUSA1221
  • Intentional mean age: 50.3
  • Unintentional mean age: 42.2

  • M: 711
  • F: 510
Intentional: 207
Accidental: 1014
  • oxycodone: 285
  • hydrocodone: 113
  • alprazolam: 278
  • clonazepam: 109
  • Antidepressants: 139
Death: 1221
Friedrich et al. [90]Retrospective database analysis of NPDS from 2000–2015USA 296,838
  • 0–2: 50,399
  • 2–6: 98,552
  • 6–12: 17,900
  • 12–18: 129,987

Gender not stated
Intentional: 142,482
Accidental: 154,356
  • alprazolam: 58,404
  • clonazepam: 53,836
  • lorazepam: 28,164
  • Another benzodiazepine: 156,434
Death: 253
  • Due to multiple drugs: 252
Torrents et al. [67]A 6-year prospective national study. Patients identified using records reported to poison centre and contacted to complete surveyFrance87Mean age 2
(0.5–17 years)
  • M: 40
  • F: 47
Accidental: 87
  • methadone: 87
Emergency unit: 42
Paediatric unit: 21
ICU: 13
Death: 5
Toce et al. [91]Retrospective cohort study at a single paediatric tertiary care centre of children between 6 months and 7 years between 2006–2014USA 88Mean age: 2
(10 months–6.4 years)
  • M: 45
  • F: 43
Accidental: 88
  • buprenorphine: 88
Hospitalised: 88
  • Respiratory depression: 73
  • Hypoxia: 25
  • Depressed mental status: 70
  • Agitation: 4
  • Misosis: 68
  • Emesis: 40
Gomes et al. [59]Population-based cross-sectional study of patients admitted for acute care in hospitals across Canada due to prescribed opioidsCanada 2599
  • 0–24: 332
  • 25–34: 419
  • 35–44: 373
  • 45–64: 979
  • 65+: 496

  • M: 1338
  • F: 1261
Accidental: 648
Intentional: 291
Unknown: 248
  • oxycodone: 294
  • fentanyl: 114
  • hydromorphone: 379
  • codeine: 199
  • morphine: 189
  • methadone: 205
  • buprenorphine: 22
  • tramadol: 27
  • Unknown: 12
Hospitalised: 2599
Shipton et al. [74]Population based cohort study using records from the Coronial Services Office in Wellington from 2008–2012New Zealand325
  • 0–9: 2
  • 10–19: 7
  • 20–29: 31
  • 30–39: 71
  • 40–49: 98
  • 50–59: 70
  • 60–69: 26
  • 70–79: 9
  • >80: 11
Unintentional: 179
Intentional: 110
Unknown: 37
  • methadone: 99
  • Opioids: 226
Death: 325
Tadros et al. [92]Retrospective study using data from the Nationwide ED Sample (NEDS) from 2006–2012USA 21,928Mean age: 9 (0–17)
  • M: 10,528
  • F: 11,390
Intentional: 5316
Accidental: 13,524
Unknown: 2126
  • Opioids: 21,928
All ED visits
  • Treated and released: 15,585
  • Admitted: 3464

Deaths: 11
Tadros et al. [93]Retrospective cohort study utilising 2006–2011 data from the Nationwide ED SampleUSA 259,093
  • 18–30: 60,709
  • 31–40: 42,197
  • 41–50: 56,900
  • 51–60: 52,548
  • 61–70: 26,146
  • 71–80: 12,640
  • 81–90: 6886
  • 91–100: 1046

  • M: 123,398

  • F: 135,654
Unintentional: 138,603
Intentional: 68,641
Unknown: 51,849
  • Opioids: 259,093
All ED visits
  • Treated & released: 108,504
  • Average charge treated in ED:
$3,515.27
  • Admitted: 140,396
  • Average charge $27,491.87 for those admitted
Vakkalanka et al. [99]Retrospective review of loperamide exposures reported to NPDS between 2010 and 2015.USA 1736
  • <5: 5
  • 6–12: 52
  • 13–19: 331
  • 20–39: 652
  • 40–59: 355
  • >60: 257
  • Unknown: 84

  • M: 749
  • F: 980
Abuse: 228
Misuse: 569
Attempted suicide: 848
Other: 91
  • loperamide: 870
  • loperamide and co-ingestion with antihistamines, antipsychotics, antidepressants, alcohol, opioids, cough and cold remedies: 866
PSS
  • No effect: 299
  • Minor effect: 387
  • Moderate effect: 384
  • Major effect: 126
  • Death: 15
Creswell et al. [126]Cross sectional study. Data of children aged 0–19 exposed to opioids was collected using hospital admissions and Wisconsin Poison Control Centre (WPC)USA3320
  • 0–5: 2019
  • 6–12: 339
  • 13–19: 962

  • M: 1634

  • F: 1681
Accidental: 2522
  • ADRi: 35
  • Therapeutic error: 613
Intentional: 748
  • Suicide attempt: 353
Unknown: 50
  • oxycodone: 361
  • tramadol: 352
  • Other prescription opioids: 2336
  • Opioid/paracetamol combination: 1679
  • Unknown: 428
ICU: 3320
Death: 3
Feingold et al. [70]Retrospective study. Data was obtained from the National database on causes of death. Drug poisoning deaths were coded as opioid-relatedIsrael875
  • 15–24: 63
  • 25–34: 142
  • 35–44: 113
  • 45–54: 78
  • 55+: 26

  • M: 362
  • F: 60
Accidental: 9
Intentional: 4
Unknown: 409
  • Opioids: 875
  • Death: 875
Koskela et al. [65]Retrospective study. Data was collected from Cause of Death Registry death certificates provided by Statistics Finland from 2007–2011.Northern Finland684Urban:
  • mean age: 47.5 (36–57)
  • M: 292
  • F: 104

Rural:
  • mean age: 52 (44–59)
  • M: 226
  • F: 62
Urban:
Intentional (suicide attempt): 82

Rural:
Intentional (suicide attempt): 40
Urban:
  • Benzodiazepine: 20
  • Antidepressants: 35
  • Antiepileptics: 33
  • paracetamol: 69
  • Insulin: 6
  • CVS acting drugs: 10
Rural:
  • Benzodiazepine: 6
  • Antidepressants: 13
  • Antiepileptics: 19
  • paracetamol: 1
  • Insulin: 3
  • CVS acting drugs: 5
Death: 684
Tobaiqy et al. [82]Retrospective study. Chart review of all acute paediatric poisoning incidence in ED at East Jeddah Hospital over 4-year period Saudi Arabia69
  • 0–5: 41
  • 6–11: 18
  • 12–16: 10

  • M: 38
  • F: 31
Accidental: 46
  • Therapeutic errors
Intentional: 5unknown: 18
  • Analgesics: 27
  • Anticonvulsant: 13
  • Antipsychotic: 9
  • CVS medicine: 3
  • Antihistamine: 1
  • Unknown: 16
Hospitalised: 69
  • Admitted to paediatric ward: 25
  • paediatric ICU: 8

Death: 1
Kriikku et al. [66]Retrospective review of post-mortem toxicology cases positive for urinary buprenorphine between 2010–2014Finland775Mean age: 31
  • M: 690
  • F: 85
Accidental: 463
Intentional parenteral instead of sublingual: 167
suicide: 90
other: 55
  • buprenorphine: 775
Death: 369
Thongprayoon et al. [127]Retrospective review. Data extracted from the National Inpatient Sample (NIS) coded as ICD-9 diagnosis.USA13,805
  • <20: 3902
  • 20–29: 3228
  • 30–39: 1951
  • >40: 4710

  • M: 4810
  • F: 8994
Intentional (suicide attempt): 9029
Unknown: 4776
  • aspirin: 13,805
Hospitalised: 13,805
  • Mean hospital stay: 2 days
  • >1 organ failure: 2761

Death: 132
Miller et al. [102]Prospective cross-sectional study. Analysis of censuses of live emergency department and inpatient discharges for 11 USA states as well as Multiple Cause of Death census data between 2011–2012USA10,525
  • 6–14: 26
  • 15–20: 274
  • 21–25: 571
  • 26–30: 783
  • 31–39: 1687
  • 40–49: 2207
  • 50–59: 2726
  • >60: 2251

  • M: 5660
  • F: 4865
Intentional (suicide attempt): 6716

Unknown: 3809
  • Antiemetic: 813
  • Antidepressant: 1714
  • Antidiabetic: 117
  • Antiepileptic: 688
  • Antiparkinsonian: 123
  • Barbiturate: 157
  • Benzodiazepine: 1551
  • Antispasmodic: 219
  • Opioid: 4386
  • NSAIDS: 105
  • Psychostimulant: 417
  • Antipsychotic: 653
  • Unknown: 4562
Death: 10,525
Manini et al. [128]Prospective cohort study looking at two tertiary care hospitals over 12 months.USA274Mean age: 40.3
  • M: 172
  • F: 102
Intentional: 217
Accidental: 57
  • Benzodiazepines: 59
  • Opioids: 54
  • Sympathomimetic: 50
  • paracetamol-containing: 50
  • Antidepressant: 40
Hospitalised: 274
  • MI injury: 12
  • Shock: 3
  • Dysrhythmia: 2
  • Cardiac arrest: 3

Death: 2
Lee et al. [57]Retrospective review using data from calls to Victorian Poisons Information Centre (VPIC) over a 10-year period.Australia 4412
  • 5–14 years: 37
  • 15–19 years: 325
  • 20–74 years: 2152
  • >75 years: 7
  • unknown: 889

  • M: 1084
  • F: 2307
Accidental: 781
  • Therapeutic error: 517
  • ADR: 17
Intentional: 3631
  • Misuse: 221
  • quetiapine: 4412

co-ingested with:
  • Antidepressant: 827
  • Benzodiazepine: 800
  • paracetamol: 296
  • Antiepileptics: 248
  • Antipsychotics other than quetiapine: 240
  • Opioids: 155
  • NSAIDs: 116
  • Hypnotics: 104
  • Mood stabiliser: 87
Hospitalised: 4412
Death: 1066
Vilay et al. [129]Retrospective case-control study of exposures reported to the NPDS between 2001–2007USA9074
  • <18 years: 971
  • >18 years: 7811
  • Mean age: 44.3

  • M: 5468
  • F: 3591
Intentional: 5009
Accidental: 3152
  • Cardiac drugs: 506
  • paracetamol: 946
  • Salicylates: 450
  • lithium: 995
  • ibuprofen: 324
  • Stimulants: 841
  • Opioids: 620
  • Anti-infectives: 453
  • Antiepileptics: 284
  • Antipsychotics: 355
  • Anxiolytics: 286
  • Antihistamine: 473
  • Anticholinergics: 341
  • Diuretics: 1296
  • Other: 4270
  • ICU: 6326
  • Admitted to ward: 1387
  • Admitted to psychiatric facility: 137
  • Kidney injury: 9074
Wheatley et al. [130]Retrospective review of poison centre records between 2001–2010USA162Mean age: 27
  • M: 100
  • F: 62
Intentional: 49
Accidental: 113
  • Antiretrovirals: 162
ICU: 9
Coma: 1
Kominek et al. [75]Retrospective analysis of patients hospitalised with paracetamol poisoning in a Paediatric Clinic between 2004–2012Poland44
  • Accidental mean age: 3
  • Intentional mean age: 15
  • (2–18)

  • M: 7
  • F: 37
Intentional: 30
Accidental: 10
Dosing error: 4
  • paracetamol: 44
Hospitalised: 44
Haoka et al. [73]Retrospective observational study analysisng medical records in a single tertiary hospital in JapanJapan145
  • 65–74: 47
  • 75–84: 61
  • 85–100: 37

  • M: 54
  • F: 91
Accidental: 102
Intentional: 43
  • Benzodiazepine: 59
  • Antihypertensive: 18
  • Antipsychotic: 17
  • Antiarrhythmic: 14
  • theophylline: 8
  • Antidepressants: 7
  • Antihistamines: 3
  • Other hypnotics: 3
  • Opioid: 2
  • Other: 14
Hospital visits: 145
  • Outpatient: 80
  • Inpatient care: 65
  • Average length of hospital stay was 13.9 days (1–91 days)
Mroczkowska-Juchkiewicz et al. [76]Retrospective evaluation of intentional poisoning cases in department of paediatrics, Childrens University Hospital in Lubin from 2007–2012Poland145Mean age: 15.1
(12–15)
  • M: 14
  • F: 131
Intentional: 145
reasons including psychiatric disorders, family conflicts, school conflicts, sexual assault, lack of self-acceptance from chronic disease
  • Co-ingestion: 46
  • CNS drugs: 52
  • paracetamol: 17
  • NSAIDs: 20
  • CVS drugs: 3
  • Antibiotics: 1
  • Chemotherapy: 3
  • Vitamins: 1
  • Laxatives: 2
  • Respiratory drugs: 1
Hospitalisation: 145
  • Acute hepatic failure: 2
Lasoff et al. [98]Retrospective review using state-wide poison control system electronic database from 2002–2015USA224Mean age: 41
(18–90)
  • M: 103
  • F: 121
Intentional.
  • Abuse: 8
  • Misuse: 71
  • Suicide: 83
  • Unknown: 62
  • loperamide: 224
Hospitalised: 64
  • Cardiotoxicity: 9

Deaths: 3
Feng et al. [131]Cross-sectional study. Cases were identified from a database by ICD-9-CM diagnosis codesUSA9647
  • <20: 691
  • 20–34: 3361
  • 35–54: 2947
  • 55+: 2648

  • M: 4632
  • F: 5015
Accidental: 2305
ADR: 1663
Suicidal: 930
  • Opioids: 9647
Death: 53
Lavon et al. [71]Prospective observational follow-up study of all medication errors outside healthcare facilities reported to IPICIsrael1381
  • <6 years: 814
  • >6 years: 397
  • unknown: 170

  • M: 673
  • F: 708
Accidental (therapeutic error): 1381
  • Analgesic: 378
  • Antibiotic: 169
  • ENT preparations: 96
  • Vitamins: 99
  • Cold and cough preparations: 88
  • Topical drugs: 65
  • CVS medications: 56
  • Sympathomimetic: 68
  • Antihistamines: 40
  • Hormones: 30
  • Other: 292
  • Tachycardia: 6
  • Hypotension: 4
  • Sedation: 18
  • Vomiting: 11
  • Abdominal pain: 10
  • Nausea: 6
  • Throat irritation: 3
  • Eye irritation: 14
  • Restlessness: 9
  • Weakness: 8
Hospitalised: 11
Stevens et al. [68]Retrospective study analysing metformin poisoning reported to Western France PCC from 1999–2016France382
  • <15: 94
  • 15–75: 221
  • >75: 61
  • Mean age 44.7

  • M: 174
  • F: 208
Accidental: 197
Intentional: 127
Therapeutic error: 58
  • metformin: 382
  • ICU admission: 90
  • AKI: 79
  • CV shock: 21
  • MALA: 63

Death: 21
Torrents et al. [69]Retrospective descriptive study of cases of methadone exposure reported to French poison centres over a 7-year-period France 1415Mean age: 34
(10–74)
  • M: 1001
  • F: 414
Misuse: 670
Suicide attempt: 584
Unintentional: 12
Medication errors: 140
  • methadone: 1415
  • Coma: 511
  • Seizure: 57
  • Somnolence: 949
  • Miosis: 598
  • GI effects: 140
  • Respiratory effects: 113

Death: 219
Zakharov et al. [61]Retrospective review using the database of the Czech Toxicological Information Centre from 2007–2011Czech Republic2339
  • 9–13: 316
  • 14–18: 2023

  • M: 526
  • F: 1813
Intentional (suicide attempt): 2339
  • CNS drugs: 912
  • NSAIDs: 261
  • Respiratory: 119
  • CVS drugs: 64
  • Antibiotics: 37
  • Co-ingestions: 709
  • Unknown: 205
Medical care: 2339
Caupp et al. [100]Retrospective review using Poison Control Centre Data in Ohio from 2002–2014USA 619
  • 10–14: 82
  • 15–17: 224
  • 18–24: 417
  • 25–29: 344

  • M: 484
  • F: 423
Accidental: 97
Intentional: 504
Other/unknown: 37
  • tramadol: 125
  • paracetamol with hydrocodone: 112
  • paracetamol with oxycodone: 70
  • oxycodone: 35
  • buprenorphine: 30
  • co-codamol: 20
  • methadone: 18
  • morphine: 10
  • Antidiarrheals: 7
  • Others 125
PSS:
  • No effect: 144
  • Minor: 319
  • Moderate: 287
  • Major: 83
  • Unknown: 213
  • Death: 9
Okic et al. [103]Retrospective review of descents from forensic pathology in Kansas City autopsied between 2001–2011USA 789Mean age: 43
(2–92)
  • M: 508
  • F: 281
Accident 332
Intentional (suicide attempt): 43
Unknown: 101
  • fentanyl: 180
  • methadone: 299
  • oxycodone: 310
Death: 789
Christenses et al. [63]Retrospective review looking at enquires concerning CBBs reported to the Danish Poisons Information Centre (DPIC) from 2009–2015Denmark 339
  • <16: 78
  • >16: 261

  • M: 146
  • F: 193
Intentional (suicide attempt): 156

Accidental: 183
CCB;
  • amlodipine: 249
  • verapamil: 45
  • felodipine: 16
  • diltiazem: 16
  • Other: 13
Hospitalised: 275
  • Average length of stay: 1 day

Death: 7
Truitt et al. [132]Retrospective chart review of PCC charts by running a search on all calls received between 2007–2009USA 436
  • <50: 85
  • >50: 351
  • Mean age: 65.1 (2–91)

  • M: 152
  • F: 28
Accidental: 436
  • BB: 258
  • CCB: 178
Hospitalised: 32
Death: 1
Christensen et al. [64]Retrospective study of drug poisoning cases reported to Danish Poison Information Centre (DPIC)Denmark 239
  • 0–6: 12
  • 7–12: 6
  • 13–25: 135
  • 26–65: 82
  • 65+: 4

  • M: 57
  • F: 182
Intentional (suicide attempt): 175
Accidental: 64
aripiprazole: 239
combined with:
  • Antipsychotic: 78
  • Antidepressant: 72
  • Antiepileptic: 32
  • Benzodiazepine: 37
  • zolpidem or zopiclone: 15
  • paracetamol: 21
Hospital visits: 239
  • Sedation: 204
  • Tremor: 158
  • Survived: 239
King et al. [101]Retrospective review of NPDS data from 2000–2014 to identify paediatric ADHD medication exposures USA 156,365
  • 0–5: 8891
  • 6–12: 59,953
  • 13–19: 37,521

  • M: 102,150
  • F: 53,970
Accidental: 128,119
Intentional: 23,034
ADR: 4040
Unknown: 1172
  • methylphenidate: 72,267
  • amphetamine: 69,642
  • atomoxetine: 13,303
  • modafinil: 1153
PSS:
  • No effect: 47,549
  • Minor effect: 24,658
  • Moderate effect: 14,285
  • Major effect: 481
  • Death: 3
Vohra et al. [95]Retrospective study of exposures using electronic health records and reports to NPDS (2004–2014)USA99
  • <4 years: 92
  • 5–12 years: 7
  • Mean age: 1

  • M: 55
  • F: 44
Accidental: 88
  • Therapeutic error: 6
  • ADR: 4
Unknown: 1
  • benzocaine gel: 99
  • No effect: 74
  • Minor effect: 16
  • Moderate effect: 3
  • Major effect: 5
Lin et al. [84]Retrospective evaluation of medical records of children under 18 who presented to the ED with pharmaceutical poisoning (2001–2008) Taiwan87Mean age: 11.26
  • M: 39
  • F: 48
Accidental: 34
Intentional: 53
  • CNS agent: 42
  • Analgesic: 16
  • Respiratory: 6
  • CVS agent: 7
  • Vitamins: 6
  • Others: 10
Hospitalised: 87
  • POU observation: 60
  • Discharged from ED: 6
  • ICU: 4
  • Accidental average length of stay: 20.79 h
  • Intentional length of stay: 37.74 h
Conner et al. [96]Retrospective review of intentional self-poisoning (ISP) cases aged 13–65 treated at a USA University Medical CentreUSA673
  • 13–18: 218
  • 19–65: 455

  • M: 237
  • F: 436
Intentional (suicide attempt): 673
  • Analgesic: 176
  • Anticholinergic: 142
  • Anticonvulsant: 46
  • Antidepressant: 209
  • Antipsychotic: 90
  • CVS drugs: 65
  • lithium: 20
  • Opioid: 68
  • Hypnotic: 182
  • Sympathomimetic: 66
PSS:
  • Minor effect: 390
  • Moderate effect: 281
  • Deaths: 4
Piotrowska et al. [79]Retrospective, observational study of patients presenting to ED of Bern University Hospital. Cases were identified using electronic database. Switzerland181Mean age: 25
(16–85)
  • M: 43
  • F: 138
Accidental: 38
Intentional: 143
  • paracetamol: 181
Hospitalised: 181
  • Average hospital length of stay: 2 days

Deaths: 2
Patel et al. [97]Retrospective, cross-sectional analysis using NPDS from 2010–2014 identifying patients <18 years with exposure to opioid.USA 83,418
  • 0–1: 5042
  • 1–2: 32,204
  • 3–5: 13,744
  • 6–12: 8819
  • 13–17: 23,245

  • M: 41,081
  • F: 42,022
Accidental: 61,206
Intentional: 20,064
ADR: 1088
Other: 227
  • Opioids: 83,418
PSS:
  • No effect: 32,944
  • Minor: 32,443
  • Moderate: 7709
  • Major: 1368
  • Death: 111
Reichert et al. [80]Retrospective review of acute single-agent exposures to pharmaceutical reported to Swiss Toxicological Information Centre (STIC) between 1997–2012Switzerland 313
  • 0–4: 14
  • 5–9: 2
  • 10–14: 12
  • 15–19: 83
  • 20–90: 193

  • M: 94
  • F: 219
Accidental: 42
Intentional: 266
Other: 5
  • Antidepressants: 136
  • Antipsychotics: 30
  • Antiepileptics: 17
  • Opioids: 15
  • methadone: 3
  • NSAIDs: 51
  • Other: 61
Seizures: 313
Sinyor et al. [60]Retrospective review of drug induced suicides in Toronto using Coroner’s dataCanada397
  • <20: 1
  • 20–39: 109
  • 40–59: 199
  • 60–79: 70
  • >80: 17

  • M: 199
  • F: 197
Intentional (suicide attempt): 397
  • Opioids: 112
  • Anxiolytics: 105
  • OTC medicines: 85
  • TCA: 81
  • SSRI: 14
Death: 397
Glaizal et al. [133]Retrospective review using results of a 2-year national survey by the toxicovigilance network (2008–2010)USA 135Mean age: 31
(13–58)
  • M: 99
  • F: 36
Intentional (suicide attempt): 135
  • methadone: 135
ED: 85
ICU: 38
Death: 10
Cassidy et al. [77]Prospective study over 3-years on medication errors reported to NPICRepublic of Ireland 2348
  • <1: 291
  • 1–4: 619
  • 5–9: 185
  • 10–17: 125
  • 18–64: 450
  • 64–80: 184
  • 80+: 130
  • Unknown: 364

  • M: 1043
  • F: 1256
Accidental (medication error): 2348
  • Analgesics: 362
  • Antipsychotics: 163
  • Anti-epileptics: 90
  • NSAIDs: 206
  • Respiratory: 102
  • Antibiotics: 263
  • Contraceptives: 54
  • Opioids: 52
  • ACEIs: 50
  • Cough and cold: 149
  • Antihistamines: 136
  • Dermatologic: 55
  • Iron: 29
  • Vitamins: 20
PSS:
  • No effect: 864
  • Symptomatic: 259
ED: 179
Calcaterra et al. [134]Retrospective chart review of data from NPDS between 2001–2014USA188,452Mean age: 31.5
  • M: 101,943
  • F: 85,580
  • Unknown: 929
Intentional: 188,452
  • Opioid: 57,338
  • Benzodiazepine: 95,353
  • Opioid and benzodiazepine: 20,555
Coma: 6264
Respiratory depression: 6766
Death: 124
Eigner et al. [135]Retrospective review of overdose deaths using Indiana State Department of Health death certificates available through Allen County Coroner’s Office.USA 418
  • 15–24: 32
  • 25–34: 86
  • 35–44: 92
  • 45–54: 123
  • 55–64: 54
  • 64–74: 10
  • 75–85: 3

  • M: 249
  • F: 169
Accidental: 336
Intentional: 66
Unknown: 16
  • Opioids
  • Benzodiazepines
  • Antipsychotics
  • Antidepressants
  • Anticonvulsants
  • Analgesics
Death: 418
* Where available, age ranges are displayed in brackets below the noted age categories and mean age of the sample size. a USA: United States of America; UK: United Kingdom. b M:male; F: female. c NSAIDS: non-steroidal anti-inflammatory drugs; CVS: cardiovascular; GI: gastrointestinal; CCB: calcium channel blocker; BB: beta blocker; CNS: central nervous system; OTC: over the counter; TCA: tricyclic antidepressant; SSRI: selective serotonin reuptake inhibitor; ACEI: angiotensin-converting enzyme inhibitor. d PICU: Paediatric intensive care unit; ICU: Intensive care unit; ED: emergency department; ADR: adverse drug reaction; MI: myocardial infarction; ENT: ear nose and throat; AKI: acute kidney injury; MALA: metformin associated lactic acidosis; POU: Pyrexia of unknown origin; PSS: Poisoning severity score.

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Figure 1. PRISMA-ScR flowchart of study selection.
Figure 1. PRISMA-ScR flowchart of study selection.
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Figure 2. Comparing the reason behind pharmaceutical poisoning between LMIC and HIC’s.
Figure 2. Comparing the reason behind pharmaceutical poisoning between LMIC and HIC’s.
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Table 1. Search terms.
Table 1. Search terms.
Poison TermsPharmaceutical Terms
Poison *Pharmaceutical
ToxicMedicine
OverdoseDrug
IntoxicationOpioid
Excessive
Substance abuse
Drug Misuse
Table 2. List of all countries and their economic status where studies were conducted.
Table 2. List of all countries and their economic status where studies were conducted.
Low-Middle-Income Countries (n = 21)High-Income Countries * (n = 58)
Algeria: 1 [38]
Argentina: 1 [39]
India: 2 [40,41]
Iran: 9 [42,43,44,45,46,47,48,49]
Jordan: 1 [50]
Morocco: 1 [51]
Romania: 1 [52]
South Africa: 1 [11]
Sri Lanka: 1 [53]
Turkey: 3 [54,55]
Australia: 2 [56,57]
Canada: 3 [58,59,60]
Czech Republic: 1 [61]
Denmark: 3 [62,63,64]
Finland: 2 [65,66]
France: 3 [67,68,69]
Israel: 2 [70,71]
Japan: 2 [72,73]
New Zealand: 1 [74]
Poland: 2 [75,76]
Republic of Ireland: 1 [77]
Switzerland: 4 [78,79,80]
Saudi Arabia: 2 [81,82]
Singapore: 1 [83]
Taiwan: 1 [84]
UK: 1 [85]
USA: 27 [86,87,88,89,90,91,92,93]
* United Kingdom = UK; United States of America = USA.
Table 3. Drugs responsible for poisoning in LMICs and HICs grouped into the ATC 1st level categories *.
Table 3. Drugs responsible for poisoning in LMICs and HICs grouped into the ATC 1st level categories *.
ATC 1st Level ClassificationLMIC (n)HIC (n)
A. Alimentary tract and metabolism3362721
B. Blood and blood forming organs1529
C. Cardiovascular system1932947
D. Dermatological0219
G. Genito urinary system and sex hormones6079
H. Systemic hormonal preparations, excluding sex hormones and insulins6630
J. Anti-infective for systemic use185635
L. Antineoplastic and immunomodulating agents043
M. Musculo-skeletal system49637,736
N. Nervous System30961,365,780
R. Respiratory system4782775
Combination of pharmaceuticals ingested84427,168
* Classification is according to the organ or system that the drugs therapeutically target.
Table 4. Drugs responsible for poisoning in LMIC and HIC studies categorised into the ATC 2nd level classification for drugs acting on the nervous system.
Table 4. Drugs responsible for poisoning in LMIC and HIC studies categorised into the ATC 2nd level classification for drugs acting on the nervous system.
Nervous SystemLMIC (n, %)HIC (n, %)
Analgesics1236 (39.9)783,654 (57.3)
Antiepileptics287 (9.27) 1194 (0.87)
Anti-Parkinson drugs0 (0)194 (0.01)
Psycholeptics618 (20.0)105,036 (7.69)
Psychoanaleptics383 (12.4)461,019 (33.8)
Drugs used in opioid dependence572 (18.5)14,683 (10.8)
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Cowans, C.; Love, A.; Tangiisuran, B.; Jacob, S.A. Uncovering the Hidden Burden of Pharmaceutical Poisoning in High-Income and Low-Middle-Income Countries: A Scoping Review. Pharmacy 2023, 11, 184. https://doi.org/10.3390/pharmacy11060184

AMA Style

Cowans C, Love A, Tangiisuran B, Jacob SA. Uncovering the Hidden Burden of Pharmaceutical Poisoning in High-Income and Low-Middle-Income Countries: A Scoping Review. Pharmacy. 2023; 11(6):184. https://doi.org/10.3390/pharmacy11060184

Chicago/Turabian Style

Cowans, Claire, Anya Love, Balamurugan Tangiisuran, and Sabrina Anne Jacob. 2023. "Uncovering the Hidden Burden of Pharmaceutical Poisoning in High-Income and Low-Middle-Income Countries: A Scoping Review" Pharmacy 11, no. 6: 184. https://doi.org/10.3390/pharmacy11060184

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