Frequently used drug types and alcohol involvement in intentional drug overdoses in Ireland: a national registry study

Frequently used drug types and alcohol involvement in intentional drug overdoses in Ireland: a... Abstract Background Intentional drug overdose (IDO) is the most common form of hospital-treated self-harm, yet no national study has systematically classified the range of drugs involved using a validated system. We aimed to determine the profile of patients engaging in overdose, to identify drugs frequently used and to quantify the contributions of multiple drug use and alcohol involvement. Methods Between 2012 and 2014, the National Self-Harm Registry, Ireland recorded 18 329 presentations of non-fatal IDO to Irish emergency departments. Information on demographic and overdose characteristics were obtained. Drugs were categorized using the Anatomical Therapeutic Chemical classification system. Results Analgesics (32.4%), antidepressants (21.9%), anxiolytics (21.2%) and hypnotics and sedatives (21.0%) were the most frequently used drugs types involved in overdose. Presentations involving analgesic and antidepressant medication were more common for females whereas males more often took illegal, anxiolytic and hypnotic and sedative drugs. Overdoses with drugs other than those which affect the nervous system were identified, including musculoskeletal drugs, taken in 12.0% of presentations. Paracetamol was the most frequently used drug, particularly among females (32.0%) and persons under 25 years (36.2%). Alcohol was most often present in overdoses involving anxiolytics and illegal drugs. Multiple drug use was a factor in almost half (47.1%) of presentations. Conclusions People who engage in IDO frequently take prescription only or sales restricted drugs, often involving alcohol and/or multiple drug use. These findings highlight the importance of addressing drug and alcohol misuse, potential inappropriate prescribing and the enforcement of legislation restricting specific drug sales. Introduction The individual and societal impact of non-fatal intentional drug overdose (IDO) is significant. Its association with morbidity, repeat self-harm and suicide is well established.1–4 IDO is the most common form of hospital treated self-harm, involved in 65–85% of presentations in Oxford, Manchester and Derby as reported by the Multicentre self-harm study,5,6 and in Ireland by the National Self-Harm Registry.7 Most commonly enacted by females and by persons aged under 45 years,1 IDO is associated with multiple drug use and alcohol consumption.2,8 Alcohol is involved in between 43% and 59% of self-harm presentations1,8,9 and is of concern due to the increased lethality of IDOs involving alcohol,10 its association with complications in medical treatment and the increased risk of long-term alcohol related death among persons who self-harm involving alcohol.11 Psychotropic and analgesic drugs currently represent the most frequently reported drug types involved in IDO.1,2,12–14 Approximately one-third of IDOs in Ireland entail the use of minor tranquillisers,7 whereas paracetamol-containing medication are more common in IDO in England, as per the Multicentre study.6,15 Additionally, benzodiazepines and antipsychotics are associated with misuse and frequent use in IDO.16,17 Multiple drug use is an important factor in IDO, involved in 18–26% of presentations, with implications for patient treatment, outcome and controlling access to drugs.9,17 Earlier research indicates that the frequency and trends of drugs taken in IDO reflects their availability and prescribing in a population.13,18–21 This association presents an opportunity for means restriction interventions, for which a current and comprehensive evidence-base regarding drugs used in IDO is essential. Studies conducted to date generally apply ad hoc classifications to drugs used in IDO, based on what are assumed to be the most common drug groups. This method of classification does not allow for the complete examination of all drugs used, resulting in up to one-quarter of drugs (19–25%) being represented within a large miscellaneous ‘other drugs’ category.1,13 Moreover, these classifications often do not include drugs other than those that affect the nervous system including, for example those intended to treat musculoskeletal, cardiovascular and respiratory disorders. Finally, the use of non-standardized classifications also restricts the comparability of information regarding drugs used across surveillance systems and registries. The Anatomical Therapeutic Chemical (ATC) system is a World Health Organization (WHO) recommended classification system designed to measure drug utilization at an internationally comparable level.22 This is the first known study of a national self-harm surveillance system to examine drugs taken in IDO according to the ATC system. The application of this system is progressive in this area as it will provide an up-to-date, standardized and complete breakdown of all drugs used in IDO, necessary to inform suicide and self-harm research, intervention and policy, while facilitating comparative drug utilization research between countries and across healthcare settings. This national study examines the clinical and socio-demographic profile of patients who engage in IDO, detailing drugs used according to their ATC classification with a particular focus on quantifying the contributions of multiple drug use and alcohol involvement. Methods National Self-Harm Registry, Ireland This is a national system that monitors the occurrence of hospital-treated self-harm. Since 2006 the Registry has collected self-harm data from all 36 acute hospitals across the Republic of Ireland. This study examines presentations of IDO for the period 1 January 2012 to 31 December 2014. Data collection is carried out by trained Data Registration Officers (DROs). Cases of self-harm are independently identified and recorded by DROs using a combination of manual and electronic checks of emergency department presentations. For a full description of data items and procedures of the Registry, please refer to Perry et al.7 Recording of self-harm methods Cases of IDO include those with ICD-10 codes of X60–X64 (overdose of drugs and medicaments). Presentations of accidental overdose with prescribed medications intended to treat specific illnesses or with illegal drugs used for recreational purposes and poisonings of undetermined intent (ICD-10 codes Y10–Y19), were not included. Cases involving other poisoning agents and alcohol-only self-poisoning cases were excluded. Drug names and quantity of tablets ingested, involving up to 13 drugs, are captured via self-reported information from the patient, ambulance service records, hospital medical records and toxicology reports where present. Alcohol involvement prior to or during the act of IDO is captured through hospital case notes as recorded on registration or by the attending clinician, or if present in toxicology reports. Classification of drugs taken in IDO using the ATC system The ATC system categorizes drugs according to the system or organ upon which they act, stratifying them according to their chemical, pharmacological and therapeutic properties, the detail of which can be found in the Guidelines for ATC Classification.22 An ATC code was applied to all drugs examined by the researcher (CD) with validation cross-checks provided by a co-author (DMA) who is a qualified pharmacist. Drugs classified within the ATC system may be used for two or more equally important indications. Such drugs were attributed one code, based on its main indication, as determined by the literature.22 Drugs were classified according to their use at the time of ATC system application, December 2016. Illegal drugs were identified using the Misuse of Drugs Acts.23,24 In accordance with these Acts, we identified illegal drugs as those with no or very little medicinal purposes. For IDOs involving intravenous illegal drugs, the quantities taken were recorded as missing. As a result of self-report, 2005 (10.9%) of drugs taken were reported as ‘unknown’. For a further 593 (3.2%) of drugs recorded the classification of ‘unknown’ was attributed to them as it was not possible to apply an ATC code based on limited information available. In the context of this paper, multiple drug use refers to the use of two or more drugs other than alcohol involved in a presentation. Single drug use refers to the use of just one drug type, other than alcohol, per presentation. Ethical approval and data protection The Registry has ethical approval from the National Research Ethics Committee of the Faculty of Public Health Medicine. The National Suicide Research Foundation is registered with the Data Protection Agency and complies with the Irish Data Protection Act of 1988 and the Irish Data Protection (Amendment) Act of 2003. Statistical analysis and reporting Statistical analyses were conducted using IBM SPSS version 22.0. We applied a threshold of P < 0.01 to signify statistical significance. Due to the large sample size in this study many outcomes were found to be statistically significant at P < 0.05 but overall the magnitude of identified differences was small. Where presentation numbers fell below 5 data was not published to protect the identity of individuals. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Results Profile of persons engaging in IDO During the study period 1 January 2012 to 31 December 2014 there were 18 329 self-harm presentations involving IDO, representing 67.6% of all self-harm presentations. The majority (58.7%) of presentations were made by females. As described in table 1, presentations were proportionately highest among persons aged 15–24 years (28.3%), and decreased with increasing age. The majority of IDO presentations involved overdose only (89.5%) with self-cutting identified as the most common combined method, involved in 6.5% of IDOs. Alcohol was present in 40.6% of IDOs, more common in male presentations (44.7% vs. 37.8%, x2=86.82, df = 1, P < 0.01) and highest among those aged 25–34 years (25.1%, x2=619.61, df = 5, P < 0.01). Almost half (47.1%) of presentations involved more than one drug type. The median number of total tablets taken per IDO case was 23 for males (IQR: 12–40) and 20 for females (IQR: 12–35). Over one-third of presentations involved the ingestion of between 20 and 49 tablets (36.7%) and 14.0% of presentations involved 50 or more tablets. Table 1 Characteristics of Intentional Drug Overdose (IDO) involvement in self-harm acts, 2012–14 Demographics  Male N (%)  Female N (%)  Total N (%)  7562 (41.3)  10 767 (58.7)  18 329  Age, median (IQR)  32 (23, 43)  33 (22, 45)  33 (23, 45)      <15 years  73 (1.0)  349 (3.2)  422 (2.3)      15–24  2105 (27.8)  3090 (28.7)  5195 (28.3)      25–34  2041 (27.0)  2330 (21.6)  4371 (23.8)      35–44  1613 (21.3)  2132 (19.8)  3745 (20.4)      45–54  1088 (14.4)  1790 (16.6)  2878 (15.7)      55+  642 (8.5)  1076 (10.0)  1718 (9.4)  IDO and self-cutting  549 (7.3)  634 (5.9)  1183 (6.5)  Alcohol involvement            All ages  3377 (44.7)  4069 (37.8)  7446 (40.6)      <15 years  8 (0.2)  18 (0.4)  26 (0.3)      15–24  786 (23.3)  817 (20.1)  1603 (21.5)      25–34  908 (26.9)  963 (23.7)  1871 (25.1)      35–44  824 (24.4)  1003 (24.6)  1827 (24.5)      45–54  560 (16.6)  865 (21.3)  1425 (19.1)      55+  291 (8.6)  403 (9.9)  694 (9.3)  Number of drug types            1 drug type  4077 (53.9)  5613 (52.1)  9690 (52.9)      2 or more  3485 (46.1)  5154 (47.9)  8639 (47.1)      3 or more  1597 (21.1)  2557 (23.7)  4154 (22.7)      4 or more  631 (8.3)  1077 (10.0)  1708 (9.3)      5 or more  184 (2.4)  310 (2.9)  494 (2.7)  Multiple drug use            All ages  3485 (46.1)  5154 (47.9)  8639 (47.1)      <15 years  28 (0.8)  121 (2.3)  149 (1.7)      15–24  889 (25.5)  1381 (26.8)  2270 (26.3)      25–34  956 (27.4)  1192 (23.1)  2148 (24.9)      35–44  796 (22.8)  1092 (21.2)  1888 (21.9)      45–54  513 (14.7)  881 (17.1)  1394 (16.1)      55+  303 (8.7)  487 (9.4)  790 (9.1)  Number of tablets, median (IQR)a  23 (12, 40)  20 (12, 35)  20 (12, 37)  Number of tablets            <10 tabletsa  1603 (27.3)  2104 (24.1)  3707 (25.3)      10–19  1206 (20.5)  2304 (26.3)  3510 (24.0)      20–49  2133 (36.3)  3238 (37.0)  5371 (36.7)      50+  939 (16.0)  1102 (12.6)  2041 (14.0)  Demographics  Male N (%)  Female N (%)  Total N (%)  7562 (41.3)  10 767 (58.7)  18 329  Age, median (IQR)  32 (23, 43)  33 (22, 45)  33 (23, 45)      <15 years  73 (1.0)  349 (3.2)  422 (2.3)      15–24  2105 (27.8)  3090 (28.7)  5195 (28.3)      25–34  2041 (27.0)  2330 (21.6)  4371 (23.8)      35–44  1613 (21.3)  2132 (19.8)  3745 (20.4)      45–54  1088 (14.4)  1790 (16.6)  2878 (15.7)      55+  642 (8.5)  1076 (10.0)  1718 (9.4)  IDO and self-cutting  549 (7.3)  634 (5.9)  1183 (6.5)  Alcohol involvement            All ages  3377 (44.7)  4069 (37.8)  7446 (40.6)      <15 years  8 (0.2)  18 (0.4)  26 (0.3)      15–24  786 (23.3)  817 (20.1)  1603 (21.5)      25–34  908 (26.9)  963 (23.7)  1871 (25.1)      35–44  824 (24.4)  1003 (24.6)  1827 (24.5)      45–54  560 (16.6)  865 (21.3)  1425 (19.1)      55+  291 (8.6)  403 (9.9)  694 (9.3)  Number of drug types            1 drug type  4077 (53.9)  5613 (52.1)  9690 (52.9)      2 or more  3485 (46.1)  5154 (47.9)  8639 (47.1)      3 or more  1597 (21.1)  2557 (23.7)  4154 (22.7)      4 or more  631 (8.3)  1077 (10.0)  1708 (9.3)      5 or more  184 (2.4)  310 (2.9)  494 (2.7)  Multiple drug use            All ages  3485 (46.1)  5154 (47.9)  8639 (47.1)      <15 years  28 (0.8)  121 (2.3)  149 (1.7)      15–24  889 (25.5)  1381 (26.8)  2270 (26.3)      25–34  956 (27.4)  1192 (23.1)  2148 (24.9)      35–44  796 (22.8)  1092 (21.2)  1888 (21.9)      45–54  513 (14.7)  881 (17.1)  1394 (16.1)      55+  303 (8.7)  487 (9.4)  790 (9.1)  Number of tablets, median (IQR)a  23 (12, 40)  20 (12, 35)  20 (12, 37)  Number of tablets            <10 tabletsa  1603 (27.3)  2104 (24.1)  3707 (25.3)      10–19  1206 (20.5)  2304 (26.3)  3510 (24.0)      20–49  2133 (36.3)  3238 (37.0)  5371 (36.7)      50+  939 (16.0)  1102 (12.6)  2041 (14.0)  a Number of tablets was known for 14 628 (79.8%) of all presentations. Table 1 Characteristics of Intentional Drug Overdose (IDO) involvement in self-harm acts, 2012–14 Demographics  Male N (%)  Female N (%)  Total N (%)  7562 (41.3)  10 767 (58.7)  18 329  Age, median (IQR)  32 (23, 43)  33 (22, 45)  33 (23, 45)      <15 years  73 (1.0)  349 (3.2)  422 (2.3)      15–24  2105 (27.8)  3090 (28.7)  5195 (28.3)      25–34  2041 (27.0)  2330 (21.6)  4371 (23.8)      35–44  1613 (21.3)  2132 (19.8)  3745 (20.4)      45–54  1088 (14.4)  1790 (16.6)  2878 (15.7)      55+  642 (8.5)  1076 (10.0)  1718 (9.4)  IDO and self-cutting  549 (7.3)  634 (5.9)  1183 (6.5)  Alcohol involvement            All ages  3377 (44.7)  4069 (37.8)  7446 (40.6)      <15 years  8 (0.2)  18 (0.4)  26 (0.3)      15–24  786 (23.3)  817 (20.1)  1603 (21.5)      25–34  908 (26.9)  963 (23.7)  1871 (25.1)      35–44  824 (24.4)  1003 (24.6)  1827 (24.5)      45–54  560 (16.6)  865 (21.3)  1425 (19.1)      55+  291 (8.6)  403 (9.9)  694 (9.3)  Number of drug types            1 drug type  4077 (53.9)  5613 (52.1)  9690 (52.9)      2 or more  3485 (46.1)  5154 (47.9)  8639 (47.1)      3 or more  1597 (21.1)  2557 (23.7)  4154 (22.7)      4 or more  631 (8.3)  1077 (10.0)  1708 (9.3)      5 or more  184 (2.4)  310 (2.9)  494 (2.7)  Multiple drug use            All ages  3485 (46.1)  5154 (47.9)  8639 (47.1)      <15 years  28 (0.8)  121 (2.3)  149 (1.7)      15–24  889 (25.5)  1381 (26.8)  2270 (26.3)      25–34  956 (27.4)  1192 (23.1)  2148 (24.9)      35–44  796 (22.8)  1092 (21.2)  1888 (21.9)      45–54  513 (14.7)  881 (17.1)  1394 (16.1)      55+  303 (8.7)  487 (9.4)  790 (9.1)  Number of tablets, median (IQR)a  23 (12, 40)  20 (12, 35)  20 (12, 37)  Number of tablets            <10 tabletsa  1603 (27.3)  2104 (24.1)  3707 (25.3)      10–19  1206 (20.5)  2304 (26.3)  3510 (24.0)      20–49  2133 (36.3)  3238 (37.0)  5371 (36.7)      50+  939 (16.0)  1102 (12.6)  2041 (14.0)  Demographics  Male N (%)  Female N (%)  Total N (%)  7562 (41.3)  10 767 (58.7)  18 329  Age, median (IQR)  32 (23, 43)  33 (22, 45)  33 (23, 45)      <15 years  73 (1.0)  349 (3.2)  422 (2.3)      15–24  2105 (27.8)  3090 (28.7)  5195 (28.3)      25–34  2041 (27.0)  2330 (21.6)  4371 (23.8)      35–44  1613 (21.3)  2132 (19.8)  3745 (20.4)      45–54  1088 (14.4)  1790 (16.6)  2878 (15.7)      55+  642 (8.5)  1076 (10.0)  1718 (9.4)  IDO and self-cutting  549 (7.3)  634 (5.9)  1183 (6.5)  Alcohol involvement            All ages  3377 (44.7)  4069 (37.8)  7446 (40.6)      <15 years  8 (0.2)  18 (0.4)  26 (0.3)      15–24  786 (23.3)  817 (20.1)  1603 (21.5)      25–34  908 (26.9)  963 (23.7)  1871 (25.1)      35–44  824 (24.4)  1003 (24.6)  1827 (24.5)      45–54  560 (16.6)  865 (21.3)  1425 (19.1)      55+  291 (8.6)  403 (9.9)  694 (9.3)  Number of drug types            1 drug type  4077 (53.9)  5613 (52.1)  9690 (52.9)      2 or more  3485 (46.1)  5154 (47.9)  8639 (47.1)      3 or more  1597 (21.1)  2557 (23.7)  4154 (22.7)      4 or more  631 (8.3)  1077 (10.0)  1708 (9.3)      5 or more  184 (2.4)  310 (2.9)  494 (2.7)  Multiple drug use            All ages  3485 (46.1)  5154 (47.9)  8639 (47.1)      <15 years  28 (0.8)  121 (2.3)  149 (1.7)      15–24  889 (25.5)  1381 (26.8)  2270 (26.3)      25–34  956 (27.4)  1192 (23.1)  2148 (24.9)      35–44  796 (22.8)  1092 (21.2)  1888 (21.9)      45–54  513 (14.7)  881 (17.1)  1394 (16.1)      55+  303 (8.7)  487 (9.4)  790 (9.1)  Number of tablets, median (IQR)a  23 (12, 40)  20 (12, 35)  20 (12, 37)  Number of tablets            <10 tabletsa  1603 (27.3)  2104 (24.1)  3707 (25.3)      10–19  1206 (20.5)  2304 (26.3)  3510 (24.0)      20–49  2133 (36.3)  3238 (37.0)  5371 (36.7)      50+  939 (16.0)  1102 (12.6)  2041 (14.0)  a Number of tablets was known for 14 628 (79.8%) of all presentations. Classification of drug types involved in IDO Four-fifths of IDOs (80.2%) involved drugs affecting the nervous system, with musculoskeletal system drugs present in 12.0% of presentations (table 2). Illegal drugs were involved in 6.0% of IDOs. Drugs affecting the alimentary tract and metabolism were involved in 851 presentations (4.6%) and cardiovascular system drugs were similarly common, in 3.9% of presentations. Table 2 Therapeutic drug groups involved in IDO according to ATC classification, 2012–14 Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  Total, n (%) N = 18 329  Nervous system (N)  5910 (78.2)  8793 (81.7)  14 703 (80.2)*  Musculoskeletal system (M)  698 (9.2)  1504 (14.0)  2202 (12.0)*  Illegal drugs  767 (10.1)  335 (3.1)  1102 (6.0)*  Alimentary tract and metabolism (A)  323 (4.3)  528 (4.9)  851 (4.6)  Cardiovascular system (C)  278 (3.7)  443 (4.1)  721 (3.9)  Anti-infective for systemic use (J)  170 (2.2)  367 (3.4)  537 (2.9)*  Respiratory system (R)  168 (2.2)  361 (3.4)  529 (2.9)*  Blood and blood forming organs (B)  100 (1.3)  107 (1.0)  207 (1.1)  Systemic hormonal preparations, excl. sex hormones and insulin (S)  54 (0.7)  133 (1.2)  187 (1.0)*  Genitourinary system and sex hormones (G)  23 (0.3)  56 (0.5)  79 (0.4)  Antiparasitic products, insecticides and repellents (P)  18 (0.2)  43 (0.4)  61 (0.3)  Antineoplastic and immunomodulating agents, various, sensory and dermatologicals (L, V, S, D)a  25 (0.3)  33 (0.3)  58 (0.3)  Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  Total, n (%) N = 18 329  Nervous system (N)  5910 (78.2)  8793 (81.7)  14 703 (80.2)*  Musculoskeletal system (M)  698 (9.2)  1504 (14.0)  2202 (12.0)*  Illegal drugs  767 (10.1)  335 (3.1)  1102 (6.0)*  Alimentary tract and metabolism (A)  323 (4.3)  528 (4.9)  851 (4.6)  Cardiovascular system (C)  278 (3.7)  443 (4.1)  721 (3.9)  Anti-infective for systemic use (J)  170 (2.2)  367 (3.4)  537 (2.9)*  Respiratory system (R)  168 (2.2)  361 (3.4)  529 (2.9)*  Blood and blood forming organs (B)  100 (1.3)  107 (1.0)  207 (1.1)  Systemic hormonal preparations, excl. sex hormones and insulin (S)  54 (0.7)  133 (1.2)  187 (1.0)*  Genitourinary system and sex hormones (G)  23 (0.3)  56 (0.5)  79 (0.4)  Antiparasitic products, insecticides and repellents (P)  18 (0.2)  43 (0.4)  61 (0.3)  Antineoplastic and immunomodulating agents, various, sensory and dermatologicals (L, V, S, D)a  25 (0.3)  33 (0.3)  58 (0.3)  Notes: For 2005 (10.9%) recorded drugs taken, drug names were recorded at hospital as unknown. For 593 (3.2%) of drugs recorded the classification of unknown was attributed to them as it was not possible to attribute an ATC code based on limited information. a Categories combined due to small numbers. *: Statistical significance P < 0.01. Table 2 Therapeutic drug groups involved in IDO according to ATC classification, 2012–14 Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  Total, n (%) N = 18 329  Nervous system (N)  5910 (78.2)  8793 (81.7)  14 703 (80.2)*  Musculoskeletal system (M)  698 (9.2)  1504 (14.0)  2202 (12.0)*  Illegal drugs  767 (10.1)  335 (3.1)  1102 (6.0)*  Alimentary tract and metabolism (A)  323 (4.3)  528 (4.9)  851 (4.6)  Cardiovascular system (C)  278 (3.7)  443 (4.1)  721 (3.9)  Anti-infective for systemic use (J)  170 (2.2)  367 (3.4)  537 (2.9)*  Respiratory system (R)  168 (2.2)  361 (3.4)  529 (2.9)*  Blood and blood forming organs (B)  100 (1.3)  107 (1.0)  207 (1.1)  Systemic hormonal preparations, excl. sex hormones and insulin (S)  54 (0.7)  133 (1.2)  187 (1.0)*  Genitourinary system and sex hormones (G)  23 (0.3)  56 (0.5)  79 (0.4)  Antiparasitic products, insecticides and repellents (P)  18 (0.2)  43 (0.4)  61 (0.3)  Antineoplastic and immunomodulating agents, various, sensory and dermatologicals (L, V, S, D)a  25 (0.3)  33 (0.3)  58 (0.3)  Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  Total, n (%) N = 18 329  Nervous system (N)  5910 (78.2)  8793 (81.7)  14 703 (80.2)*  Musculoskeletal system (M)  698 (9.2)  1504 (14.0)  2202 (12.0)*  Illegal drugs  767 (10.1)  335 (3.1)  1102 (6.0)*  Alimentary tract and metabolism (A)  323 (4.3)  528 (4.9)  851 (4.6)  Cardiovascular system (C)  278 (3.7)  443 (4.1)  721 (3.9)  Anti-infective for systemic use (J)  170 (2.2)  367 (3.4)  537 (2.9)*  Respiratory system (R)  168 (2.2)  361 (3.4)  529 (2.9)*  Blood and blood forming organs (B)  100 (1.3)  107 (1.0)  207 (1.1)  Systemic hormonal preparations, excl. sex hormones and insulin (S)  54 (0.7)  133 (1.2)  187 (1.0)*  Genitourinary system and sex hormones (G)  23 (0.3)  56 (0.5)  79 (0.4)  Antiparasitic products, insecticides and repellents (P)  18 (0.2)  43 (0.4)  61 (0.3)  Antineoplastic and immunomodulating agents, various, sensory and dermatologicals (L, V, S, D)a  25 (0.3)  33 (0.3)  58 (0.3)  Notes: For 2005 (10.9%) recorded drugs taken, drug names were recorded at hospital as unknown. For 593 (3.2%) of drugs recorded the classification of unknown was attributed to them as it was not possible to attribute an ATC code based on limited information. a Categories combined due to small numbers. *: Statistical significance P < 0.01. Nervous system drugs involved in IDO The most commonly taken drugs in IDO are described in table 3. Hypnotic and sedative drugs were involved in approximately one-fifth (21.0%) of IDOs. Benzodiazepine derivatives were involved in over one in three presentations (36.4%). Analgesics were taken in almost one-third of IDOs (32.4%). Antidepressants were involved in more than one in five (21.9%) presentations. Antiepileptic drugs were involved in 8.9% of IDOs (table 4), of which the many were either pregabalin or gabapentin (49.5%). Table 3 Nervous system and illegal drugs involved in IDO by gender, age, alcohol and multiple drug use, 2012–14 Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Alcohol involvement, n (%)  Multiple drug use, n (%)  Nervous system (N)  5910 (78.2)  8793 (81.7)  4332 (77.1)  6592 (81.2)  3779 (82.2)*  14 703 (80.2)*  6186 (42.1)  8095 (55.1)  Psycholeptics (N05)  3521 (46.6)  4336 (40.3)  1682 (29.9)  3830 (47.2)  2345 (51.0)*  7857 (42.9)*  3568 (45.4)  5185 (66.0)      Anxiolytics (N05B)  1832 (24.2)  2062 (19.2)  888 (15.8)  1963 (24.2)  1043 (22.7)*  3894 (21.2)*  1920 (49.3)  2677 (68.7)      Hypnotics and sedatives (N05C)  1610 (21.3)  2248 (20.9)  694 (12.4)  1836 (22.6)  1328 (28.9)*  3858 (21.0)  1736 (45.0)  2765 (71.7)      Antipsychotics (N05A)  769 (10.2)  1036 (9.6)  367 (6.5)  927 (11.4)  511 (11.1)*  1805 (9.8)  588 (32.6)  1441 (79.8)  Analgesics (N02)  2020 (26.7)  3923 (36.4)  2240 (39.9)  2392 (29.5)  1311 (28.5)*  5943 (32.4)*  2186 (36.8)  3515 (59.1)      Other analgesics and antipyretics (N02B)  1745 (23.1)  3576 (33.2)  2099 (37.4)  2069 (25.5)  1153 (25.1)*  5321 (29.0)*  1931 (36.3)  3082 (57.9)      Opioids (N02A)  342 (4.5)  484 (4.5)  206 (3.7)  420 (5.2)  200 (4.4)*  826 (4.5)  335 (40.6)  643 (77.8)      Antimigraine preparations (N02C)  <0.1  <0.1  <0.1  <0.1  <0.1  18 (0.1)  (<17.0)  17 (94.4)  Psychoanaleptics (N06)  1476 (19.5)  2604 (24.2)  1037 (18.5)  1900 (23.4)  1143 (24.9)*  4080 (22.3)*  1820 (44.6)  2991 (73.3)      Antidepressants (N06A)  1442 (19.1)  2570 (23.9)  991 (17.6)  1886 (23.2)  1135 (24.7)*  4012 (21.9)*  1804 (45.0)  2956 (73.7)      Psychostimulants, agents used for ADHD and nootropics (N06B)  34 (0.4)  41 (0.4)  51 (0.9)  17 (0.2)  7 (0.2)*  75 (0.4)  20 (26.7)  44 (58.7)      Anti-dementia drugs (N06D)  5 (0.1)  5 (0.0)  0.1  <0.1  <0.1  10 (0.1)  (<20.0)  8 (80.0)  Antiepileptics (N03)  642 (8.5)  987 (9.2)  307 (5.5)  834 (10.3)  488 (10.6)*  1629 (8.9)  604 (37.1)  1286 (78.9)  Other nervous system drugs (N07)  203 (2.7)  124 (1.2)  79 (1.4)  194 (2.4)  54 (1.2)*  327 (1.8)*  134 (41.0)  265 (81)  Anti-Parkinson (N04)  34 (0.4)  33 (0.3)  10 (0.2)  21 (0.3)  36 (0.8)*  67 (0.4)  14 (20.9)  62 (92.5)  Anaesthetics (N01)  17 (0.2)  9 (0.1)  13 (0.2)  <0.1  <0.1  26 (0.1)  9 (34.6)  17 (65.4)  Illegal drugs  767 (10.1)  335 (3.1)  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  527 (47.8)  778 (70.6)  Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Alcohol involvement, n (%)  Multiple drug use, n (%)  Nervous system (N)  5910 (78.2)  8793 (81.7)  4332 (77.1)  6592 (81.2)  3779 (82.2)*  14 703 (80.2)*  6186 (42.1)  8095 (55.1)  Psycholeptics (N05)  3521 (46.6)  4336 (40.3)  1682 (29.9)  3830 (47.2)  2345 (51.0)*  7857 (42.9)*  3568 (45.4)  5185 (66.0)      Anxiolytics (N05B)  1832 (24.2)  2062 (19.2)  888 (15.8)  1963 (24.2)  1043 (22.7)*  3894 (21.2)*  1920 (49.3)  2677 (68.7)      Hypnotics and sedatives (N05C)  1610 (21.3)  2248 (20.9)  694 (12.4)  1836 (22.6)  1328 (28.9)*  3858 (21.0)  1736 (45.0)  2765 (71.7)      Antipsychotics (N05A)  769 (10.2)  1036 (9.6)  367 (6.5)  927 (11.4)  511 (11.1)*  1805 (9.8)  588 (32.6)  1441 (79.8)  Analgesics (N02)  2020 (26.7)  3923 (36.4)  2240 (39.9)  2392 (29.5)  1311 (28.5)*  5943 (32.4)*  2186 (36.8)  3515 (59.1)      Other analgesics and antipyretics (N02B)  1745 (23.1)  3576 (33.2)  2099 (37.4)  2069 (25.5)  1153 (25.1)*  5321 (29.0)*  1931 (36.3)  3082 (57.9)      Opioids (N02A)  342 (4.5)  484 (4.5)  206 (3.7)  420 (5.2)  200 (4.4)*  826 (4.5)  335 (40.6)  643 (77.8)      Antimigraine preparations (N02C)  <0.1  <0.1  <0.1  <0.1  <0.1  18 (0.1)  (<17.0)  17 (94.4)  Psychoanaleptics (N06)  1476 (19.5)  2604 (24.2)  1037 (18.5)  1900 (23.4)  1143 (24.9)*  4080 (22.3)*  1820 (44.6)  2991 (73.3)      Antidepressants (N06A)  1442 (19.1)  2570 (23.9)  991 (17.6)  1886 (23.2)  1135 (24.7)*  4012 (21.9)*  1804 (45.0)  2956 (73.7)      Psychostimulants, agents used for ADHD and nootropics (N06B)  34 (0.4)  41 (0.4)  51 (0.9)  17 (0.2)  7 (0.2)*  75 (0.4)  20 (26.7)  44 (58.7)      Anti-dementia drugs (N06D)  5 (0.1)  5 (0.0)  0.1  <0.1  <0.1  10 (0.1)  (<20.0)  8 (80.0)  Antiepileptics (N03)  642 (8.5)  987 (9.2)  307 (5.5)  834 (10.3)  488 (10.6)*  1629 (8.9)  604 (37.1)  1286 (78.9)  Other nervous system drugs (N07)  203 (2.7)  124 (1.2)  79 (1.4)  194 (2.4)  54 (1.2)*  327 (1.8)*  134 (41.0)  265 (81)  Anti-Parkinson (N04)  34 (0.4)  33 (0.3)  10 (0.2)  21 (0.3)  36 (0.8)*  67 (0.4)  14 (20.9)  62 (92.5)  Anaesthetics (N01)  17 (0.2)  9 (0.1)  13 (0.2)  <0.1  <0.1  26 (0.1)  9 (34.6)  17 (65.4)  Illegal drugs  767 (10.1)  335 (3.1)  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  527 (47.8)  778 (70.6)  Notes: For 2005 of drugs taken, drug names were recorded as unknown. For 593 of drugs recorded, the classification of unknown was attributed to them as it was not possible to attribute another ATC code based on limited information. * Statistical significance P < 0.01. Table 3 Nervous system and illegal drugs involved in IDO by gender, age, alcohol and multiple drug use, 2012–14 Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Alcohol involvement, n (%)  Multiple drug use, n (%)  Nervous system (N)  5910 (78.2)  8793 (81.7)  4332 (77.1)  6592 (81.2)  3779 (82.2)*  14 703 (80.2)*  6186 (42.1)  8095 (55.1)  Psycholeptics (N05)  3521 (46.6)  4336 (40.3)  1682 (29.9)  3830 (47.2)  2345 (51.0)*  7857 (42.9)*  3568 (45.4)  5185 (66.0)      Anxiolytics (N05B)  1832 (24.2)  2062 (19.2)  888 (15.8)  1963 (24.2)  1043 (22.7)*  3894 (21.2)*  1920 (49.3)  2677 (68.7)      Hypnotics and sedatives (N05C)  1610 (21.3)  2248 (20.9)  694 (12.4)  1836 (22.6)  1328 (28.9)*  3858 (21.0)  1736 (45.0)  2765 (71.7)      Antipsychotics (N05A)  769 (10.2)  1036 (9.6)  367 (6.5)  927 (11.4)  511 (11.1)*  1805 (9.8)  588 (32.6)  1441 (79.8)  Analgesics (N02)  2020 (26.7)  3923 (36.4)  2240 (39.9)  2392 (29.5)  1311 (28.5)*  5943 (32.4)*  2186 (36.8)  3515 (59.1)      Other analgesics and antipyretics (N02B)  1745 (23.1)  3576 (33.2)  2099 (37.4)  2069 (25.5)  1153 (25.1)*  5321 (29.0)*  1931 (36.3)  3082 (57.9)      Opioids (N02A)  342 (4.5)  484 (4.5)  206 (3.7)  420 (5.2)  200 (4.4)*  826 (4.5)  335 (40.6)  643 (77.8)      Antimigraine preparations (N02C)  <0.1  <0.1  <0.1  <0.1  <0.1  18 (0.1)  (<17.0)  17 (94.4)  Psychoanaleptics (N06)  1476 (19.5)  2604 (24.2)  1037 (18.5)  1900 (23.4)  1143 (24.9)*  4080 (22.3)*  1820 (44.6)  2991 (73.3)      Antidepressants (N06A)  1442 (19.1)  2570 (23.9)  991 (17.6)  1886 (23.2)  1135 (24.7)*  4012 (21.9)*  1804 (45.0)  2956 (73.7)      Psychostimulants, agents used for ADHD and nootropics (N06B)  34 (0.4)  41 (0.4)  51 (0.9)  17 (0.2)  7 (0.2)*  75 (0.4)  20 (26.7)  44 (58.7)      Anti-dementia drugs (N06D)  5 (0.1)  5 (0.0)  0.1  <0.1  <0.1  10 (0.1)  (<20.0)  8 (80.0)  Antiepileptics (N03)  642 (8.5)  987 (9.2)  307 (5.5)  834 (10.3)  488 (10.6)*  1629 (8.9)  604 (37.1)  1286 (78.9)  Other nervous system drugs (N07)  203 (2.7)  124 (1.2)  79 (1.4)  194 (2.4)  54 (1.2)*  327 (1.8)*  134 (41.0)  265 (81)  Anti-Parkinson (N04)  34 (0.4)  33 (0.3)  10 (0.2)  21 (0.3)  36 (0.8)*  67 (0.4)  14 (20.9)  62 (92.5)  Anaesthetics (N01)  17 (0.2)  9 (0.1)  13 (0.2)  <0.1  <0.1  26 (0.1)  9 (34.6)  17 (65.4)  Illegal drugs  767 (10.1)  335 (3.1)  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  527 (47.8)  778 (70.6)  Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Alcohol involvement, n (%)  Multiple drug use, n (%)  Nervous system (N)  5910 (78.2)  8793 (81.7)  4332 (77.1)  6592 (81.2)  3779 (82.2)*  14 703 (80.2)*  6186 (42.1)  8095 (55.1)  Psycholeptics (N05)  3521 (46.6)  4336 (40.3)  1682 (29.9)  3830 (47.2)  2345 (51.0)*  7857 (42.9)*  3568 (45.4)  5185 (66.0)      Anxiolytics (N05B)  1832 (24.2)  2062 (19.2)  888 (15.8)  1963 (24.2)  1043 (22.7)*  3894 (21.2)*  1920 (49.3)  2677 (68.7)      Hypnotics and sedatives (N05C)  1610 (21.3)  2248 (20.9)  694 (12.4)  1836 (22.6)  1328 (28.9)*  3858 (21.0)  1736 (45.0)  2765 (71.7)      Antipsychotics (N05A)  769 (10.2)  1036 (9.6)  367 (6.5)  927 (11.4)  511 (11.1)*  1805 (9.8)  588 (32.6)  1441 (79.8)  Analgesics (N02)  2020 (26.7)  3923 (36.4)  2240 (39.9)  2392 (29.5)  1311 (28.5)*  5943 (32.4)*  2186 (36.8)  3515 (59.1)      Other analgesics and antipyretics (N02B)  1745 (23.1)  3576 (33.2)  2099 (37.4)  2069 (25.5)  1153 (25.1)*  5321 (29.0)*  1931 (36.3)  3082 (57.9)      Opioids (N02A)  342 (4.5)  484 (4.5)  206 (3.7)  420 (5.2)  200 (4.4)*  826 (4.5)  335 (40.6)  643 (77.8)      Antimigraine preparations (N02C)  <0.1  <0.1  <0.1  <0.1  <0.1  18 (0.1)  (<17.0)  17 (94.4)  Psychoanaleptics (N06)  1476 (19.5)  2604 (24.2)  1037 (18.5)  1900 (23.4)  1143 (24.9)*  4080 (22.3)*  1820 (44.6)  2991 (73.3)      Antidepressants (N06A)  1442 (19.1)  2570 (23.9)  991 (17.6)  1886 (23.2)  1135 (24.7)*  4012 (21.9)*  1804 (45.0)  2956 (73.7)      Psychostimulants, agents used for ADHD and nootropics (N06B)  34 (0.4)  41 (0.4)  51 (0.9)  17 (0.2)  7 (0.2)*  75 (0.4)  20 (26.7)  44 (58.7)      Anti-dementia drugs (N06D)  5 (0.1)  5 (0.0)  0.1  <0.1  <0.1  10 (0.1)  (<20.0)  8 (80.0)  Antiepileptics (N03)  642 (8.5)  987 (9.2)  307 (5.5)  834 (10.3)  488 (10.6)*  1629 (8.9)  604 (37.1)  1286 (78.9)  Other nervous system drugs (N07)  203 (2.7)  124 (1.2)  79 (1.4)  194 (2.4)  54 (1.2)*  327 (1.8)*  134 (41.0)  265 (81)  Anti-Parkinson (N04)  34 (0.4)  33 (0.3)  10 (0.2)  21 (0.3)  36 (0.8)*  67 (0.4)  14 (20.9)  62 (92.5)  Anaesthetics (N01)  17 (0.2)  9 (0.1)  13 (0.2)  <0.1  <0.1  26 (0.1)  9 (34.6)  17 (65.4)  Illegal drugs  767 (10.1)  335 (3.1)  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  527 (47.8)  778 (70.6)  Notes: For 2005 of drugs taken, drug names were recorded as unknown. For 593 of drugs recorded, the classification of unknown was attributed to them as it was not possible to attribute another ATC code based on limited information. * Statistical significance P < 0.01. Table 4 Drugs frequently involved in IDO, by gender and age, 2012–14 Drug  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Paracetamols (N02BE01/51)  1644 (21.7)  3443 (32.0)*  2034 (36.2)  1996 (24.6)  1057(23.0)  5087 (27.8)*  Diazepam (N05BA01)  1093 (14.5)  1007 (9.4)*  564 (10.0)  1064 (13.1)  472 (10.3)  2100 (11.5)*  Zopiclone (N05CF01)  739 (9.8)  953 (8.9)  291 (5.2)  860 (10.6)  541 (11.8)  1692 (9.2)*  Alprazolam (N05BA12)  583 (7.7)  843 (7.8)  314 (5.6)  713 (8.8)  399 (8.7)  1426 (7.8)*  Escitalopram (N06AB10)  337 (4.5)  592 (5.5)  275 (4.9)  432 (5.3)  222 (4.8)  929 (5.1)  Zolpidem (N05CF02)  288 (3.8)  559 (5.2)*  127 (2.3)  397 (4.9)  323 (7.0)  847 (4.6)*  Pregabalin (N03AX16)  331 (4.4)  470 (4.4)  129 (2.3)  424 (5.2)  248 (5.4)  801 (4.4)*  Venlafaxine (N06AX16)  206 (2.7)  426 (4.0)*  113 (2.0)  304 (3.7)  215 (4.7)  632 (3.4)*  Flurazepam (N05CD01)  255 (3.4)  369 (3.4)  111 (2.0)  289 (3.6)  224 (4.9)  624 (3.4)*  Ibuprofen (M01AE01)  366 (4.8)  846 (7.9)*  529 (9.4)  508 (6.3)  175 (3.8)  1212 (6.6)*  Diclofenac (M01AB05)  142 (1.9)  290 (2.7)*  159 (2.8)  200 (2.5)  73 (1.6)  432 (2.4)*  Illegal drugs  767 (10.1)  335 (3.1)*  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  Drug  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Paracetamols (N02BE01/51)  1644 (21.7)  3443 (32.0)*  2034 (36.2)  1996 (24.6)  1057(23.0)  5087 (27.8)*  Diazepam (N05BA01)  1093 (14.5)  1007 (9.4)*  564 (10.0)  1064 (13.1)  472 (10.3)  2100 (11.5)*  Zopiclone (N05CF01)  739 (9.8)  953 (8.9)  291 (5.2)  860 (10.6)  541 (11.8)  1692 (9.2)*  Alprazolam (N05BA12)  583 (7.7)  843 (7.8)  314 (5.6)  713 (8.8)  399 (8.7)  1426 (7.8)*  Escitalopram (N06AB10)  337 (4.5)  592 (5.5)  275 (4.9)  432 (5.3)  222 (4.8)  929 (5.1)  Zolpidem (N05CF02)  288 (3.8)  559 (5.2)*  127 (2.3)  397 (4.9)  323 (7.0)  847 (4.6)*  Pregabalin (N03AX16)  331 (4.4)  470 (4.4)  129 (2.3)  424 (5.2)  248 (5.4)  801 (4.4)*  Venlafaxine (N06AX16)  206 (2.7)  426 (4.0)*  113 (2.0)  304 (3.7)  215 (4.7)  632 (3.4)*  Flurazepam (N05CD01)  255 (3.4)  369 (3.4)  111 (2.0)  289 (3.6)  224 (4.9)  624 (3.4)*  Ibuprofen (M01AE01)  366 (4.8)  846 (7.9)*  529 (9.4)  508 (6.3)  175 (3.8)  1212 (6.6)*  Diclofenac (M01AB05)  142 (1.9)  290 (2.7)*  159 (2.8)  200 (2.5)  73 (1.6)  432 (2.4)*  Illegal drugs  767 (10.1)  335 (3.1)*  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  * Statistical significance P < 0.01. Table 4 Drugs frequently involved in IDO, by gender and age, 2012–14 Drug  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Paracetamols (N02BE01/51)  1644 (21.7)  3443 (32.0)*  2034 (36.2)  1996 (24.6)  1057(23.0)  5087 (27.8)*  Diazepam (N05BA01)  1093 (14.5)  1007 (9.4)*  564 (10.0)  1064 (13.1)  472 (10.3)  2100 (11.5)*  Zopiclone (N05CF01)  739 (9.8)  953 (8.9)  291 (5.2)  860 (10.6)  541 (11.8)  1692 (9.2)*  Alprazolam (N05BA12)  583 (7.7)  843 (7.8)  314 (5.6)  713 (8.8)  399 (8.7)  1426 (7.8)*  Escitalopram (N06AB10)  337 (4.5)  592 (5.5)  275 (4.9)  432 (5.3)  222 (4.8)  929 (5.1)  Zolpidem (N05CF02)  288 (3.8)  559 (5.2)*  127 (2.3)  397 (4.9)  323 (7.0)  847 (4.6)*  Pregabalin (N03AX16)  331 (4.4)  470 (4.4)  129 (2.3)  424 (5.2)  248 (5.4)  801 (4.4)*  Venlafaxine (N06AX16)  206 (2.7)  426 (4.0)*  113 (2.0)  304 (3.7)  215 (4.7)  632 (3.4)*  Flurazepam (N05CD01)  255 (3.4)  369 (3.4)  111 (2.0)  289 (3.6)  224 (4.9)  624 (3.4)*  Ibuprofen (M01AE01)  366 (4.8)  846 (7.9)*  529 (9.4)  508 (6.3)  175 (3.8)  1212 (6.6)*  Diclofenac (M01AB05)  142 (1.9)  290 (2.7)*  159 (2.8)  200 (2.5)  73 (1.6)  432 (2.4)*  Illegal drugs  767 (10.1)  335 (3.1)*  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  Drug  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Paracetamols (N02BE01/51)  1644 (21.7)  3443 (32.0)*  2034 (36.2)  1996 (24.6)  1057(23.0)  5087 (27.8)*  Diazepam (N05BA01)  1093 (14.5)  1007 (9.4)*  564 (10.0)  1064 (13.1)  472 (10.3)  2100 (11.5)*  Zopiclone (N05CF01)  739 (9.8)  953 (8.9)  291 (5.2)  860 (10.6)  541 (11.8)  1692 (9.2)*  Alprazolam (N05BA12)  583 (7.7)  843 (7.8)  314 (5.6)  713 (8.8)  399 (8.7)  1426 (7.8)*  Escitalopram (N06AB10)  337 (4.5)  592 (5.5)  275 (4.9)  432 (5.3)  222 (4.8)  929 (5.1)  Zolpidem (N05CF02)  288 (3.8)  559 (5.2)*  127 (2.3)  397 (4.9)  323 (7.0)  847 (4.6)*  Pregabalin (N03AX16)  331 (4.4)  470 (4.4)  129 (2.3)  424 (5.2)  248 (5.4)  801 (4.4)*  Venlafaxine (N06AX16)  206 (2.7)  426 (4.0)*  113 (2.0)  304 (3.7)  215 (4.7)  632 (3.4)*  Flurazepam (N05CD01)  255 (3.4)  369 (3.4)  111 (2.0)  289 (3.6)  224 (4.9)  624 (3.4)*  Ibuprofen (M01AE01)  366 (4.8)  846 (7.9)*  529 (9.4)  508 (6.3)  175 (3.8)  1212 (6.6)*  Diclofenac (M01AB05)  142 (1.9)  290 (2.7)*  159 (2.8)  200 (2.5)  73 (1.6)  432 (2.4)*  Illegal drugs  767 (10.1)  335 (3.1)*  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  * Statistical significance P < 0.01. Drugs most frequently involved in IDO Table 4 illustrates the individual drugs most frequently taken in IDO. Five of these are benzodiazepine derivatives and other related drugs (diazepam, zopiclone, alprazolam, zolpidem and flurazepam), cumulatively involved in 31.1% of presentations. The most frequently used drug was paracetamol, involved in 27.8% of IDOs. Anti-inflammatory drugs ibuprofen and diclofenac, and antidepressant drugs escitalopram and venlafaxine were also frequently taken in IDO (6.6%, 2.4%, 5.1% and 3.4%). Gender and age differences Significant gender differences were found in relation to drugs involved in IDO. Musculoskeletal system drugs were significantly more common in female compared with male IDOs (14.0% vs. 9.2%, x2=94.34, df = 1, P < 0.01). Similarly, IDO involving analgesics and antidepressants were significantly more common in female presentations (36.4% vs. 26.7%, x2=191.65, df = 1, P < 0.01 and 23.9% vs. 19.1%, x2=59.865, df = 1, P < 0.01) (table 3). In particular paracetamol was involved significantly more often in female IDOs (32.0% vs. 21.7%, x2=232.16, df = 1, P < 0.01). Illegal drugs were three times more common in male compared with female presentations (10.1% vs. 3.1%, x2 = 388.66, df = 1, P < 0.01) (table 2). Similarly, anxiolytic drugs were also taken significantly more frequently by males (24.2% vs. 19.2%, x2=68.388, df = 1, P < 0.01). Regarding age, those under 25 years took analgesic drugs more frequently than those within the older age groups (39.9%, x2=206.30, df = 2, P < 0.01). Paracetamol overdose was highest among persons under 25 years (36.2%, x2=292.30, df = 2, P < 0.01) and was present in 43.8% of IDOs by females aged under 25 years. Benzodiazepine involvement increased with age and was highest for those aged 45 years and over (44.3%, x2=502.16, df = 2, P < 0.01). Antidepressants were involved most commonly among those aged 45 years and over (24.7%, x2=89.17, df = 2, P < 0.01). Hypnotics and sedative use in IDO was significantly higher among those aged 45 years and over (28.9%, x2=438.00, df = 2, P < 0.01), and involved mainly sleeping sedatives zopiclone, zolpidem and flurazepam (9.2%, 4.6% and 3.4%). Alcohol involvement Alcohol involvement in IDO was significantly higher in male compared with female presentations (44.7% vs. 37.8%, x2=86.82, df = 1, P < 0.01). Alcohol was most frequently consumed in presentations involving illegal drugs (47.8%) followed by anxiolytics (49.3%, x2=154.52, df = 1, P < 0.01) (table 3). Multiple vs. single drug use As described in table 1 presentations made by those aged 15–24 years had the highest proportion of multiple drug use when compared with other age groups (26.3%, x2=74.55, df = 5, P < 0.01). The median number of tablets taken was considerably higher in multiple drug use at 27 (IQR 15–45) compared with a median of 18 (IQR 10–30) in single drug use (t = 25.112, P < 0.01). Of those who engaged in multiple drug use 59.5% took more than 20 tablets in their IDO presentation compared with 42.3% of those who engaged in single drug use (t = 9.059, P < 0.01). Discussion Key findings This is the first national study to descriptively profile IDO. The present study utilized a national self-harm surveillance system to describe the clinical and socio-demographic profile of persons engaging in IDO, to identify drugs used in overdose and to quantify the frequency of alcohol involvement and multiple drug use. We found that individuals engaging in IDO were most often female and young to middle aged. Alcohol use was particularly associated with being male and over 35 years, taken most often in presentations involving anxiolytics and illegal drugs. Multiple drug use was frequent; not gender-specific; most common in IDOs enacted by young-middle aged individuals, and associated with the consumption of greater quantities of tablets in overdose. Analgesic, antidepressant, anxiolytic and hypnotic and sedative drugs were most commonly consumed in IDO with age, gender, alcohol involvement and multiple drug use significantly impacting the frequency of their involvement. We found paracetamol to be the most frequently used drug, with a concerning proportion of young females overdosing with the drug. Building on existing literature The demographic profile of persons engaging in IDO identified by the present study is similar to that previously described.9,16,17 The involvement of alcohol combined with IDO was similar to some existing findings,6,10,17 particularly in relation to its concentration among persons aged 35–54 years.25 However, it was lower than that recently recorded by the Multicentre Self-Harm study (41% vs. 58%)8 and the Northern Ireland Registry of Self-Harm (59%).1 Our findings also quantify and elucidate multiple drug use in IDO, which was more frequent than that reported by Finkelstein et al.9 in Canada and Vancayseele et al.17 in Belgium (26% and 18%). As expected, multiple drug use was associated with higher quantities of tablets taken in overdose, which has been correlated with repeat self-harm and an increased risk of suicide.26 Our findings detailing the types of drugs used in IDO build upon those reported by Griffin et al.,1 owing to the application of ATC categorization to our data, facilitating the comprehensive identification of drugs used in IDO. The involvement of benzodiazepines in IDO was substantially higher in our study compared with their frequency as reported by the Multicentre study (36% vs. 14%).6,16 This more frequent use of benzodiazepines in IDO signals an association between these drugs and high risk of self-harm, potentially due to differences in the accessibility of these drugs, the most notable and worthy of further research would be disparities in prescribing patterns. Analgesic use in IDO in Ireland remains proportionately lower than in England (32.4% vs. 45.7%),16 which is potentially impacted by differences in access to paracetamol. In England quantities of paracetamol which can be purchased over-the-counter in pharmacy and non-pharmacy outlets exceed those available in Ireland.27 Disparities in relation to adherence to sales restriction legislation for paracetamol have been reported,28,29 with comparable research into adherence to sales restrictions in pharmacies required. This study too identifies the concerning use of paracetamol in IDO, with variations in its involvement determined by gender and age, as per previous research.17,30 Clinical and research implications The findings of this study provide detailed insights into the frequent use of prescription, sale-restricted and illegal drugs in IDO. We have identified populations at risk of taking prescription only drugs in IDO, a finding which can inform prescribing guidelines, in particular to those at risk of self-harm. New insights into the involvement of the range of drugs used in IDO highlights the need for physicians to also consider risk when prescribing for the management of mental and physical conditions. In line with evidence-based suicide prevention initiatives, physicians may benefit from additional training regarding the frequent use of particular drugs in IDO and measures to address issues with prescribing.31,32 Furthermore, the commonality of multiple drug use in our sample and the association between this and repeat self-harm and suicide,26 underlines the need to monitor the availability of multiple drug types to individuals, via prescription review, particularly to those at risk of self-harm. Means restriction has proven efficacy in relation to IDO27,32–37 and is increasingly recommended by national suicide prevention and drug strategies.38,39 The frequent use of over-the-counter and restricted-sale drugs found in this study accompanied by identified issues with adherence to paracetamol sales-restrictions28,29 highlight the need to review the operations of existing legislation and to examine new ways of preventing individuals, particular young people, from accessing excessive quantities of drugs. Considering alcohol, the specialized care needs of patients who have engaged in IDO with alcohol will require specialist training for hospital staff in the management of these patients.10 Strengths and limitations In this study, we used robust data from a national self-harm registry that is internationally exclusive to this field. The use of this national data set with full geographic coverage is unique, as endorsed by the World Health Organization.32,40 The application of the ATC classification system22 to our data is progressive as it has enabled the comprehensive examination of specific drugs taken in IDO, previously restricted by unstandardized methods of classification.1,13 Furthermore, this system presents considerable potential to facilitate comparative work with other drug utilization statistics and data sets between countries and across healthcare settings. There are a number of limitations to this study. Information collected on drugs used in IDO was self-reported. Several of the reported drugs taken in IDO may be used to treat a range of indications, therefore, we cannot directly attribute these drugs to particular disorders or make associations between certain conditions and risk of IDO. Information on the drug dosage and source, including whether or not it was prescribed to the individual is not currently collected. Conclusion This study presents a comprehensive profile of individuals presenting to hospital following IDO with respect to gender, age, alcohol involvement and multiple drug use. The findings raise important concerns regarding the use of specific prescribed drugs and patient safety which should be considered in prescribing guidelines. The frequent use of over-the-counter drugs raises concerns about adherence to and enforcement of legislation regulating the sale of certain drugs. The obligation to concurrently and effectively address the specialized care needs of IDO patients with alcohol intoxication is reiterated by our findings, requiring address in terms of resources and training. Acknowledgements The National Self-Harm Registry, Ireland is funded by the Health Service Executive’s National Office for Suicide Prevention. We thank the data registration officers for the work collecting information on self-harm presentations to hospitals across Ireland. We also thank Mr Eoin Perry who diligently assisted on data coding at the early stages of this research paper. Funding Funding for this research is provided collaboratively by the University of Manchester and the National Suicide Research Foundation, Cork, Ireland, which is in receipt of funding from the Irish Health Service Executive's National Office for Suicide Prevention. Conflicts of interest: None declared. Key points Frequently used drugs, alcohol and multiple drug use in intentional overdose are examined using a national data set. Analgesics, antidepressants, anxiolytics and hypnotic and sedatives are the most frequent drug groups taken in overdose. Paracetamol is the most common drug taken in overdose, particularly among females and those under 25 years. Alcohol and multiple drug use are common in overdose, creating specific care needs for patients. Issues with potential inappropriate prescribing and the enforcement of legislation regulating the sale of particular drugs require review. References 1 Griffin E, Corcoran P, Cassidy L, et al.   Characteristics of hospital-treated intentional drug overdose in Ireland and Northern Ireland. BMJ Open  2014; 4: e005557. Google Scholar CrossRef Search ADS PubMed  2 Hawton K, Haw C, Casey D, et al.   Self-harm in Oxford, England: epidemiological and clinical trends, 1996-2010. Soc Psychiatry Psychiatr Epidemiol  2015; 50: 695– 704. Google Scholar CrossRef Search ADS PubMed  3 Hawton K, Bergen H, Cooper J, et al.   Suicide following self-harm: findings from the Multicentre Study of self-harm in England, 2000-2012. J Affect Disord  2015; 175: 147– 51. Google Scholar CrossRef Search ADS PubMed  4 Hawton K, Saunders K, Topiwala A, Haw C. 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This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The European Journal of Public Health Oxford University Press

Frequently used drug types and alcohol involvement in intentional drug overdoses in Ireland: a national registry study

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
ISSN
1101-1262
eISSN
1464-360X
D.O.I.
10.1093/eurpub/cky031
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Abstract

Abstract Background Intentional drug overdose (IDO) is the most common form of hospital-treated self-harm, yet no national study has systematically classified the range of drugs involved using a validated system. We aimed to determine the profile of patients engaging in overdose, to identify drugs frequently used and to quantify the contributions of multiple drug use and alcohol involvement. Methods Between 2012 and 2014, the National Self-Harm Registry, Ireland recorded 18 329 presentations of non-fatal IDO to Irish emergency departments. Information on demographic and overdose characteristics were obtained. Drugs were categorized using the Anatomical Therapeutic Chemical classification system. Results Analgesics (32.4%), antidepressants (21.9%), anxiolytics (21.2%) and hypnotics and sedatives (21.0%) were the most frequently used drugs types involved in overdose. Presentations involving analgesic and antidepressant medication were more common for females whereas males more often took illegal, anxiolytic and hypnotic and sedative drugs. Overdoses with drugs other than those which affect the nervous system were identified, including musculoskeletal drugs, taken in 12.0% of presentations. Paracetamol was the most frequently used drug, particularly among females (32.0%) and persons under 25 years (36.2%). Alcohol was most often present in overdoses involving anxiolytics and illegal drugs. Multiple drug use was a factor in almost half (47.1%) of presentations. Conclusions People who engage in IDO frequently take prescription only or sales restricted drugs, often involving alcohol and/or multiple drug use. These findings highlight the importance of addressing drug and alcohol misuse, potential inappropriate prescribing and the enforcement of legislation restricting specific drug sales. Introduction The individual and societal impact of non-fatal intentional drug overdose (IDO) is significant. Its association with morbidity, repeat self-harm and suicide is well established.1–4 IDO is the most common form of hospital treated self-harm, involved in 65–85% of presentations in Oxford, Manchester and Derby as reported by the Multicentre self-harm study,5,6 and in Ireland by the National Self-Harm Registry.7 Most commonly enacted by females and by persons aged under 45 years,1 IDO is associated with multiple drug use and alcohol consumption.2,8 Alcohol is involved in between 43% and 59% of self-harm presentations1,8,9 and is of concern due to the increased lethality of IDOs involving alcohol,10 its association with complications in medical treatment and the increased risk of long-term alcohol related death among persons who self-harm involving alcohol.11 Psychotropic and analgesic drugs currently represent the most frequently reported drug types involved in IDO.1,2,12–14 Approximately one-third of IDOs in Ireland entail the use of minor tranquillisers,7 whereas paracetamol-containing medication are more common in IDO in England, as per the Multicentre study.6,15 Additionally, benzodiazepines and antipsychotics are associated with misuse and frequent use in IDO.16,17 Multiple drug use is an important factor in IDO, involved in 18–26% of presentations, with implications for patient treatment, outcome and controlling access to drugs.9,17 Earlier research indicates that the frequency and trends of drugs taken in IDO reflects their availability and prescribing in a population.13,18–21 This association presents an opportunity for means restriction interventions, for which a current and comprehensive evidence-base regarding drugs used in IDO is essential. Studies conducted to date generally apply ad hoc classifications to drugs used in IDO, based on what are assumed to be the most common drug groups. This method of classification does not allow for the complete examination of all drugs used, resulting in up to one-quarter of drugs (19–25%) being represented within a large miscellaneous ‘other drugs’ category.1,13 Moreover, these classifications often do not include drugs other than those that affect the nervous system including, for example those intended to treat musculoskeletal, cardiovascular and respiratory disorders. Finally, the use of non-standardized classifications also restricts the comparability of information regarding drugs used across surveillance systems and registries. The Anatomical Therapeutic Chemical (ATC) system is a World Health Organization (WHO) recommended classification system designed to measure drug utilization at an internationally comparable level.22 This is the first known study of a national self-harm surveillance system to examine drugs taken in IDO according to the ATC system. The application of this system is progressive in this area as it will provide an up-to-date, standardized and complete breakdown of all drugs used in IDO, necessary to inform suicide and self-harm research, intervention and policy, while facilitating comparative drug utilization research between countries and across healthcare settings. This national study examines the clinical and socio-demographic profile of patients who engage in IDO, detailing drugs used according to their ATC classification with a particular focus on quantifying the contributions of multiple drug use and alcohol involvement. Methods National Self-Harm Registry, Ireland This is a national system that monitors the occurrence of hospital-treated self-harm. Since 2006 the Registry has collected self-harm data from all 36 acute hospitals across the Republic of Ireland. This study examines presentations of IDO for the period 1 January 2012 to 31 December 2014. Data collection is carried out by trained Data Registration Officers (DROs). Cases of self-harm are independently identified and recorded by DROs using a combination of manual and electronic checks of emergency department presentations. For a full description of data items and procedures of the Registry, please refer to Perry et al.7 Recording of self-harm methods Cases of IDO include those with ICD-10 codes of X60–X64 (overdose of drugs and medicaments). Presentations of accidental overdose with prescribed medications intended to treat specific illnesses or with illegal drugs used for recreational purposes and poisonings of undetermined intent (ICD-10 codes Y10–Y19), were not included. Cases involving other poisoning agents and alcohol-only self-poisoning cases were excluded. Drug names and quantity of tablets ingested, involving up to 13 drugs, are captured via self-reported information from the patient, ambulance service records, hospital medical records and toxicology reports where present. Alcohol involvement prior to or during the act of IDO is captured through hospital case notes as recorded on registration or by the attending clinician, or if present in toxicology reports. Classification of drugs taken in IDO using the ATC system The ATC system categorizes drugs according to the system or organ upon which they act, stratifying them according to their chemical, pharmacological and therapeutic properties, the detail of which can be found in the Guidelines for ATC Classification.22 An ATC code was applied to all drugs examined by the researcher (CD) with validation cross-checks provided by a co-author (DMA) who is a qualified pharmacist. Drugs classified within the ATC system may be used for two or more equally important indications. Such drugs were attributed one code, based on its main indication, as determined by the literature.22 Drugs were classified according to their use at the time of ATC system application, December 2016. Illegal drugs were identified using the Misuse of Drugs Acts.23,24 In accordance with these Acts, we identified illegal drugs as those with no or very little medicinal purposes. For IDOs involving intravenous illegal drugs, the quantities taken were recorded as missing. As a result of self-report, 2005 (10.9%) of drugs taken were reported as ‘unknown’. For a further 593 (3.2%) of drugs recorded the classification of ‘unknown’ was attributed to them as it was not possible to apply an ATC code based on limited information available. In the context of this paper, multiple drug use refers to the use of two or more drugs other than alcohol involved in a presentation. Single drug use refers to the use of just one drug type, other than alcohol, per presentation. Ethical approval and data protection The Registry has ethical approval from the National Research Ethics Committee of the Faculty of Public Health Medicine. The National Suicide Research Foundation is registered with the Data Protection Agency and complies with the Irish Data Protection Act of 1988 and the Irish Data Protection (Amendment) Act of 2003. Statistical analysis and reporting Statistical analyses were conducted using IBM SPSS version 22.0. We applied a threshold of P < 0.01 to signify statistical significance. Due to the large sample size in this study many outcomes were found to be statistically significant at P < 0.05 but overall the magnitude of identified differences was small. Where presentation numbers fell below 5 data was not published to protect the identity of individuals. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Results Profile of persons engaging in IDO During the study period 1 January 2012 to 31 December 2014 there were 18 329 self-harm presentations involving IDO, representing 67.6% of all self-harm presentations. The majority (58.7%) of presentations were made by females. As described in table 1, presentations were proportionately highest among persons aged 15–24 years (28.3%), and decreased with increasing age. The majority of IDO presentations involved overdose only (89.5%) with self-cutting identified as the most common combined method, involved in 6.5% of IDOs. Alcohol was present in 40.6% of IDOs, more common in male presentations (44.7% vs. 37.8%, x2=86.82, df = 1, P < 0.01) and highest among those aged 25–34 years (25.1%, x2=619.61, df = 5, P < 0.01). Almost half (47.1%) of presentations involved more than one drug type. The median number of total tablets taken per IDO case was 23 for males (IQR: 12–40) and 20 for females (IQR: 12–35). Over one-third of presentations involved the ingestion of between 20 and 49 tablets (36.7%) and 14.0% of presentations involved 50 or more tablets. Table 1 Characteristics of Intentional Drug Overdose (IDO) involvement in self-harm acts, 2012–14 Demographics  Male N (%)  Female N (%)  Total N (%)  7562 (41.3)  10 767 (58.7)  18 329  Age, median (IQR)  32 (23, 43)  33 (22, 45)  33 (23, 45)      <15 years  73 (1.0)  349 (3.2)  422 (2.3)      15–24  2105 (27.8)  3090 (28.7)  5195 (28.3)      25–34  2041 (27.0)  2330 (21.6)  4371 (23.8)      35–44  1613 (21.3)  2132 (19.8)  3745 (20.4)      45–54  1088 (14.4)  1790 (16.6)  2878 (15.7)      55+  642 (8.5)  1076 (10.0)  1718 (9.4)  IDO and self-cutting  549 (7.3)  634 (5.9)  1183 (6.5)  Alcohol involvement            All ages  3377 (44.7)  4069 (37.8)  7446 (40.6)      <15 years  8 (0.2)  18 (0.4)  26 (0.3)      15–24  786 (23.3)  817 (20.1)  1603 (21.5)      25–34  908 (26.9)  963 (23.7)  1871 (25.1)      35–44  824 (24.4)  1003 (24.6)  1827 (24.5)      45–54  560 (16.6)  865 (21.3)  1425 (19.1)      55+  291 (8.6)  403 (9.9)  694 (9.3)  Number of drug types            1 drug type  4077 (53.9)  5613 (52.1)  9690 (52.9)      2 or more  3485 (46.1)  5154 (47.9)  8639 (47.1)      3 or more  1597 (21.1)  2557 (23.7)  4154 (22.7)      4 or more  631 (8.3)  1077 (10.0)  1708 (9.3)      5 or more  184 (2.4)  310 (2.9)  494 (2.7)  Multiple drug use            All ages  3485 (46.1)  5154 (47.9)  8639 (47.1)      <15 years  28 (0.8)  121 (2.3)  149 (1.7)      15–24  889 (25.5)  1381 (26.8)  2270 (26.3)      25–34  956 (27.4)  1192 (23.1)  2148 (24.9)      35–44  796 (22.8)  1092 (21.2)  1888 (21.9)      45–54  513 (14.7)  881 (17.1)  1394 (16.1)      55+  303 (8.7)  487 (9.4)  790 (9.1)  Number of tablets, median (IQR)a  23 (12, 40)  20 (12, 35)  20 (12, 37)  Number of tablets            <10 tabletsa  1603 (27.3)  2104 (24.1)  3707 (25.3)      10–19  1206 (20.5)  2304 (26.3)  3510 (24.0)      20–49  2133 (36.3)  3238 (37.0)  5371 (36.7)      50+  939 (16.0)  1102 (12.6)  2041 (14.0)  Demographics  Male N (%)  Female N (%)  Total N (%)  7562 (41.3)  10 767 (58.7)  18 329  Age, median (IQR)  32 (23, 43)  33 (22, 45)  33 (23, 45)      <15 years  73 (1.0)  349 (3.2)  422 (2.3)      15–24  2105 (27.8)  3090 (28.7)  5195 (28.3)      25–34  2041 (27.0)  2330 (21.6)  4371 (23.8)      35–44  1613 (21.3)  2132 (19.8)  3745 (20.4)      45–54  1088 (14.4)  1790 (16.6)  2878 (15.7)      55+  642 (8.5)  1076 (10.0)  1718 (9.4)  IDO and self-cutting  549 (7.3)  634 (5.9)  1183 (6.5)  Alcohol involvement            All ages  3377 (44.7)  4069 (37.8)  7446 (40.6)      <15 years  8 (0.2)  18 (0.4)  26 (0.3)      15–24  786 (23.3)  817 (20.1)  1603 (21.5)      25–34  908 (26.9)  963 (23.7)  1871 (25.1)      35–44  824 (24.4)  1003 (24.6)  1827 (24.5)      45–54  560 (16.6)  865 (21.3)  1425 (19.1)      55+  291 (8.6)  403 (9.9)  694 (9.3)  Number of drug types            1 drug type  4077 (53.9)  5613 (52.1)  9690 (52.9)      2 or more  3485 (46.1)  5154 (47.9)  8639 (47.1)      3 or more  1597 (21.1)  2557 (23.7)  4154 (22.7)      4 or more  631 (8.3)  1077 (10.0)  1708 (9.3)      5 or more  184 (2.4)  310 (2.9)  494 (2.7)  Multiple drug use            All ages  3485 (46.1)  5154 (47.9)  8639 (47.1)      <15 years  28 (0.8)  121 (2.3)  149 (1.7)      15–24  889 (25.5)  1381 (26.8)  2270 (26.3)      25–34  956 (27.4)  1192 (23.1)  2148 (24.9)      35–44  796 (22.8)  1092 (21.2)  1888 (21.9)      45–54  513 (14.7)  881 (17.1)  1394 (16.1)      55+  303 (8.7)  487 (9.4)  790 (9.1)  Number of tablets, median (IQR)a  23 (12, 40)  20 (12, 35)  20 (12, 37)  Number of tablets            <10 tabletsa  1603 (27.3)  2104 (24.1)  3707 (25.3)      10–19  1206 (20.5)  2304 (26.3)  3510 (24.0)      20–49  2133 (36.3)  3238 (37.0)  5371 (36.7)      50+  939 (16.0)  1102 (12.6)  2041 (14.0)  a Number of tablets was known for 14 628 (79.8%) of all presentations. Table 1 Characteristics of Intentional Drug Overdose (IDO) involvement in self-harm acts, 2012–14 Demographics  Male N (%)  Female N (%)  Total N (%)  7562 (41.3)  10 767 (58.7)  18 329  Age, median (IQR)  32 (23, 43)  33 (22, 45)  33 (23, 45)      <15 years  73 (1.0)  349 (3.2)  422 (2.3)      15–24  2105 (27.8)  3090 (28.7)  5195 (28.3)      25–34  2041 (27.0)  2330 (21.6)  4371 (23.8)      35–44  1613 (21.3)  2132 (19.8)  3745 (20.4)      45–54  1088 (14.4)  1790 (16.6)  2878 (15.7)      55+  642 (8.5)  1076 (10.0)  1718 (9.4)  IDO and self-cutting  549 (7.3)  634 (5.9)  1183 (6.5)  Alcohol involvement            All ages  3377 (44.7)  4069 (37.8)  7446 (40.6)      <15 years  8 (0.2)  18 (0.4)  26 (0.3)      15–24  786 (23.3)  817 (20.1)  1603 (21.5)      25–34  908 (26.9)  963 (23.7)  1871 (25.1)      35–44  824 (24.4)  1003 (24.6)  1827 (24.5)      45–54  560 (16.6)  865 (21.3)  1425 (19.1)      55+  291 (8.6)  403 (9.9)  694 (9.3)  Number of drug types            1 drug type  4077 (53.9)  5613 (52.1)  9690 (52.9)      2 or more  3485 (46.1)  5154 (47.9)  8639 (47.1)      3 or more  1597 (21.1)  2557 (23.7)  4154 (22.7)      4 or more  631 (8.3)  1077 (10.0)  1708 (9.3)      5 or more  184 (2.4)  310 (2.9)  494 (2.7)  Multiple drug use            All ages  3485 (46.1)  5154 (47.9)  8639 (47.1)      <15 years  28 (0.8)  121 (2.3)  149 (1.7)      15–24  889 (25.5)  1381 (26.8)  2270 (26.3)      25–34  956 (27.4)  1192 (23.1)  2148 (24.9)      35–44  796 (22.8)  1092 (21.2)  1888 (21.9)      45–54  513 (14.7)  881 (17.1)  1394 (16.1)      55+  303 (8.7)  487 (9.4)  790 (9.1)  Number of tablets, median (IQR)a  23 (12, 40)  20 (12, 35)  20 (12, 37)  Number of tablets            <10 tabletsa  1603 (27.3)  2104 (24.1)  3707 (25.3)      10–19  1206 (20.5)  2304 (26.3)  3510 (24.0)      20–49  2133 (36.3)  3238 (37.0)  5371 (36.7)      50+  939 (16.0)  1102 (12.6)  2041 (14.0)  Demographics  Male N (%)  Female N (%)  Total N (%)  7562 (41.3)  10 767 (58.7)  18 329  Age, median (IQR)  32 (23, 43)  33 (22, 45)  33 (23, 45)      <15 years  73 (1.0)  349 (3.2)  422 (2.3)      15–24  2105 (27.8)  3090 (28.7)  5195 (28.3)      25–34  2041 (27.0)  2330 (21.6)  4371 (23.8)      35–44  1613 (21.3)  2132 (19.8)  3745 (20.4)      45–54  1088 (14.4)  1790 (16.6)  2878 (15.7)      55+  642 (8.5)  1076 (10.0)  1718 (9.4)  IDO and self-cutting  549 (7.3)  634 (5.9)  1183 (6.5)  Alcohol involvement            All ages  3377 (44.7)  4069 (37.8)  7446 (40.6)      <15 years  8 (0.2)  18 (0.4)  26 (0.3)      15–24  786 (23.3)  817 (20.1)  1603 (21.5)      25–34  908 (26.9)  963 (23.7)  1871 (25.1)      35–44  824 (24.4)  1003 (24.6)  1827 (24.5)      45–54  560 (16.6)  865 (21.3)  1425 (19.1)      55+  291 (8.6)  403 (9.9)  694 (9.3)  Number of drug types            1 drug type  4077 (53.9)  5613 (52.1)  9690 (52.9)      2 or more  3485 (46.1)  5154 (47.9)  8639 (47.1)      3 or more  1597 (21.1)  2557 (23.7)  4154 (22.7)      4 or more  631 (8.3)  1077 (10.0)  1708 (9.3)      5 or more  184 (2.4)  310 (2.9)  494 (2.7)  Multiple drug use            All ages  3485 (46.1)  5154 (47.9)  8639 (47.1)      <15 years  28 (0.8)  121 (2.3)  149 (1.7)      15–24  889 (25.5)  1381 (26.8)  2270 (26.3)      25–34  956 (27.4)  1192 (23.1)  2148 (24.9)      35–44  796 (22.8)  1092 (21.2)  1888 (21.9)      45–54  513 (14.7)  881 (17.1)  1394 (16.1)      55+  303 (8.7)  487 (9.4)  790 (9.1)  Number of tablets, median (IQR)a  23 (12, 40)  20 (12, 35)  20 (12, 37)  Number of tablets            <10 tabletsa  1603 (27.3)  2104 (24.1)  3707 (25.3)      10–19  1206 (20.5)  2304 (26.3)  3510 (24.0)      20–49  2133 (36.3)  3238 (37.0)  5371 (36.7)      50+  939 (16.0)  1102 (12.6)  2041 (14.0)  a Number of tablets was known for 14 628 (79.8%) of all presentations. Classification of drug types involved in IDO Four-fifths of IDOs (80.2%) involved drugs affecting the nervous system, with musculoskeletal system drugs present in 12.0% of presentations (table 2). Illegal drugs were involved in 6.0% of IDOs. Drugs affecting the alimentary tract and metabolism were involved in 851 presentations (4.6%) and cardiovascular system drugs were similarly common, in 3.9% of presentations. Table 2 Therapeutic drug groups involved in IDO according to ATC classification, 2012–14 Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  Total, n (%) N = 18 329  Nervous system (N)  5910 (78.2)  8793 (81.7)  14 703 (80.2)*  Musculoskeletal system (M)  698 (9.2)  1504 (14.0)  2202 (12.0)*  Illegal drugs  767 (10.1)  335 (3.1)  1102 (6.0)*  Alimentary tract and metabolism (A)  323 (4.3)  528 (4.9)  851 (4.6)  Cardiovascular system (C)  278 (3.7)  443 (4.1)  721 (3.9)  Anti-infective for systemic use (J)  170 (2.2)  367 (3.4)  537 (2.9)*  Respiratory system (R)  168 (2.2)  361 (3.4)  529 (2.9)*  Blood and blood forming organs (B)  100 (1.3)  107 (1.0)  207 (1.1)  Systemic hormonal preparations, excl. sex hormones and insulin (S)  54 (0.7)  133 (1.2)  187 (1.0)*  Genitourinary system and sex hormones (G)  23 (0.3)  56 (0.5)  79 (0.4)  Antiparasitic products, insecticides and repellents (P)  18 (0.2)  43 (0.4)  61 (0.3)  Antineoplastic and immunomodulating agents, various, sensory and dermatologicals (L, V, S, D)a  25 (0.3)  33 (0.3)  58 (0.3)  Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  Total, n (%) N = 18 329  Nervous system (N)  5910 (78.2)  8793 (81.7)  14 703 (80.2)*  Musculoskeletal system (M)  698 (9.2)  1504 (14.0)  2202 (12.0)*  Illegal drugs  767 (10.1)  335 (3.1)  1102 (6.0)*  Alimentary tract and metabolism (A)  323 (4.3)  528 (4.9)  851 (4.6)  Cardiovascular system (C)  278 (3.7)  443 (4.1)  721 (3.9)  Anti-infective for systemic use (J)  170 (2.2)  367 (3.4)  537 (2.9)*  Respiratory system (R)  168 (2.2)  361 (3.4)  529 (2.9)*  Blood and blood forming organs (B)  100 (1.3)  107 (1.0)  207 (1.1)  Systemic hormonal preparations, excl. sex hormones and insulin (S)  54 (0.7)  133 (1.2)  187 (1.0)*  Genitourinary system and sex hormones (G)  23 (0.3)  56 (0.5)  79 (0.4)  Antiparasitic products, insecticides and repellents (P)  18 (0.2)  43 (0.4)  61 (0.3)  Antineoplastic and immunomodulating agents, various, sensory and dermatologicals (L, V, S, D)a  25 (0.3)  33 (0.3)  58 (0.3)  Notes: For 2005 (10.9%) recorded drugs taken, drug names were recorded at hospital as unknown. For 593 (3.2%) of drugs recorded the classification of unknown was attributed to them as it was not possible to attribute an ATC code based on limited information. a Categories combined due to small numbers. *: Statistical significance P < 0.01. Table 2 Therapeutic drug groups involved in IDO according to ATC classification, 2012–14 Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  Total, n (%) N = 18 329  Nervous system (N)  5910 (78.2)  8793 (81.7)  14 703 (80.2)*  Musculoskeletal system (M)  698 (9.2)  1504 (14.0)  2202 (12.0)*  Illegal drugs  767 (10.1)  335 (3.1)  1102 (6.0)*  Alimentary tract and metabolism (A)  323 (4.3)  528 (4.9)  851 (4.6)  Cardiovascular system (C)  278 (3.7)  443 (4.1)  721 (3.9)  Anti-infective for systemic use (J)  170 (2.2)  367 (3.4)  537 (2.9)*  Respiratory system (R)  168 (2.2)  361 (3.4)  529 (2.9)*  Blood and blood forming organs (B)  100 (1.3)  107 (1.0)  207 (1.1)  Systemic hormonal preparations, excl. sex hormones and insulin (S)  54 (0.7)  133 (1.2)  187 (1.0)*  Genitourinary system and sex hormones (G)  23 (0.3)  56 (0.5)  79 (0.4)  Antiparasitic products, insecticides and repellents (P)  18 (0.2)  43 (0.4)  61 (0.3)  Antineoplastic and immunomodulating agents, various, sensory and dermatologicals (L, V, S, D)a  25 (0.3)  33 (0.3)  58 (0.3)  Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  Total, n (%) N = 18 329  Nervous system (N)  5910 (78.2)  8793 (81.7)  14 703 (80.2)*  Musculoskeletal system (M)  698 (9.2)  1504 (14.0)  2202 (12.0)*  Illegal drugs  767 (10.1)  335 (3.1)  1102 (6.0)*  Alimentary tract and metabolism (A)  323 (4.3)  528 (4.9)  851 (4.6)  Cardiovascular system (C)  278 (3.7)  443 (4.1)  721 (3.9)  Anti-infective for systemic use (J)  170 (2.2)  367 (3.4)  537 (2.9)*  Respiratory system (R)  168 (2.2)  361 (3.4)  529 (2.9)*  Blood and blood forming organs (B)  100 (1.3)  107 (1.0)  207 (1.1)  Systemic hormonal preparations, excl. sex hormones and insulin (S)  54 (0.7)  133 (1.2)  187 (1.0)*  Genitourinary system and sex hormones (G)  23 (0.3)  56 (0.5)  79 (0.4)  Antiparasitic products, insecticides and repellents (P)  18 (0.2)  43 (0.4)  61 (0.3)  Antineoplastic and immunomodulating agents, various, sensory and dermatologicals (L, V, S, D)a  25 (0.3)  33 (0.3)  58 (0.3)  Notes: For 2005 (10.9%) recorded drugs taken, drug names were recorded at hospital as unknown. For 593 (3.2%) of drugs recorded the classification of unknown was attributed to them as it was not possible to attribute an ATC code based on limited information. a Categories combined due to small numbers. *: Statistical significance P < 0.01. Nervous system drugs involved in IDO The most commonly taken drugs in IDO are described in table 3. Hypnotic and sedative drugs were involved in approximately one-fifth (21.0%) of IDOs. Benzodiazepine derivatives were involved in over one in three presentations (36.4%). Analgesics were taken in almost one-third of IDOs (32.4%). Antidepressants were involved in more than one in five (21.9%) presentations. Antiepileptic drugs were involved in 8.9% of IDOs (table 4), of which the many were either pregabalin or gabapentin (49.5%). Table 3 Nervous system and illegal drugs involved in IDO by gender, age, alcohol and multiple drug use, 2012–14 Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Alcohol involvement, n (%)  Multiple drug use, n (%)  Nervous system (N)  5910 (78.2)  8793 (81.7)  4332 (77.1)  6592 (81.2)  3779 (82.2)*  14 703 (80.2)*  6186 (42.1)  8095 (55.1)  Psycholeptics (N05)  3521 (46.6)  4336 (40.3)  1682 (29.9)  3830 (47.2)  2345 (51.0)*  7857 (42.9)*  3568 (45.4)  5185 (66.0)      Anxiolytics (N05B)  1832 (24.2)  2062 (19.2)  888 (15.8)  1963 (24.2)  1043 (22.7)*  3894 (21.2)*  1920 (49.3)  2677 (68.7)      Hypnotics and sedatives (N05C)  1610 (21.3)  2248 (20.9)  694 (12.4)  1836 (22.6)  1328 (28.9)*  3858 (21.0)  1736 (45.0)  2765 (71.7)      Antipsychotics (N05A)  769 (10.2)  1036 (9.6)  367 (6.5)  927 (11.4)  511 (11.1)*  1805 (9.8)  588 (32.6)  1441 (79.8)  Analgesics (N02)  2020 (26.7)  3923 (36.4)  2240 (39.9)  2392 (29.5)  1311 (28.5)*  5943 (32.4)*  2186 (36.8)  3515 (59.1)      Other analgesics and antipyretics (N02B)  1745 (23.1)  3576 (33.2)  2099 (37.4)  2069 (25.5)  1153 (25.1)*  5321 (29.0)*  1931 (36.3)  3082 (57.9)      Opioids (N02A)  342 (4.5)  484 (4.5)  206 (3.7)  420 (5.2)  200 (4.4)*  826 (4.5)  335 (40.6)  643 (77.8)      Antimigraine preparations (N02C)  <0.1  <0.1  <0.1  <0.1  <0.1  18 (0.1)  (<17.0)  17 (94.4)  Psychoanaleptics (N06)  1476 (19.5)  2604 (24.2)  1037 (18.5)  1900 (23.4)  1143 (24.9)*  4080 (22.3)*  1820 (44.6)  2991 (73.3)      Antidepressants (N06A)  1442 (19.1)  2570 (23.9)  991 (17.6)  1886 (23.2)  1135 (24.7)*  4012 (21.9)*  1804 (45.0)  2956 (73.7)      Psychostimulants, agents used for ADHD and nootropics (N06B)  34 (0.4)  41 (0.4)  51 (0.9)  17 (0.2)  7 (0.2)*  75 (0.4)  20 (26.7)  44 (58.7)      Anti-dementia drugs (N06D)  5 (0.1)  5 (0.0)  0.1  <0.1  <0.1  10 (0.1)  (<20.0)  8 (80.0)  Antiepileptics (N03)  642 (8.5)  987 (9.2)  307 (5.5)  834 (10.3)  488 (10.6)*  1629 (8.9)  604 (37.1)  1286 (78.9)  Other nervous system drugs (N07)  203 (2.7)  124 (1.2)  79 (1.4)  194 (2.4)  54 (1.2)*  327 (1.8)*  134 (41.0)  265 (81)  Anti-Parkinson (N04)  34 (0.4)  33 (0.3)  10 (0.2)  21 (0.3)  36 (0.8)*  67 (0.4)  14 (20.9)  62 (92.5)  Anaesthetics (N01)  17 (0.2)  9 (0.1)  13 (0.2)  <0.1  <0.1  26 (0.1)  9 (34.6)  17 (65.4)  Illegal drugs  767 (10.1)  335 (3.1)  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  527 (47.8)  778 (70.6)  Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Alcohol involvement, n (%)  Multiple drug use, n (%)  Nervous system (N)  5910 (78.2)  8793 (81.7)  4332 (77.1)  6592 (81.2)  3779 (82.2)*  14 703 (80.2)*  6186 (42.1)  8095 (55.1)  Psycholeptics (N05)  3521 (46.6)  4336 (40.3)  1682 (29.9)  3830 (47.2)  2345 (51.0)*  7857 (42.9)*  3568 (45.4)  5185 (66.0)      Anxiolytics (N05B)  1832 (24.2)  2062 (19.2)  888 (15.8)  1963 (24.2)  1043 (22.7)*  3894 (21.2)*  1920 (49.3)  2677 (68.7)      Hypnotics and sedatives (N05C)  1610 (21.3)  2248 (20.9)  694 (12.4)  1836 (22.6)  1328 (28.9)*  3858 (21.0)  1736 (45.0)  2765 (71.7)      Antipsychotics (N05A)  769 (10.2)  1036 (9.6)  367 (6.5)  927 (11.4)  511 (11.1)*  1805 (9.8)  588 (32.6)  1441 (79.8)  Analgesics (N02)  2020 (26.7)  3923 (36.4)  2240 (39.9)  2392 (29.5)  1311 (28.5)*  5943 (32.4)*  2186 (36.8)  3515 (59.1)      Other analgesics and antipyretics (N02B)  1745 (23.1)  3576 (33.2)  2099 (37.4)  2069 (25.5)  1153 (25.1)*  5321 (29.0)*  1931 (36.3)  3082 (57.9)      Opioids (N02A)  342 (4.5)  484 (4.5)  206 (3.7)  420 (5.2)  200 (4.4)*  826 (4.5)  335 (40.6)  643 (77.8)      Antimigraine preparations (N02C)  <0.1  <0.1  <0.1  <0.1  <0.1  18 (0.1)  (<17.0)  17 (94.4)  Psychoanaleptics (N06)  1476 (19.5)  2604 (24.2)  1037 (18.5)  1900 (23.4)  1143 (24.9)*  4080 (22.3)*  1820 (44.6)  2991 (73.3)      Antidepressants (N06A)  1442 (19.1)  2570 (23.9)  991 (17.6)  1886 (23.2)  1135 (24.7)*  4012 (21.9)*  1804 (45.0)  2956 (73.7)      Psychostimulants, agents used for ADHD and nootropics (N06B)  34 (0.4)  41 (0.4)  51 (0.9)  17 (0.2)  7 (0.2)*  75 (0.4)  20 (26.7)  44 (58.7)      Anti-dementia drugs (N06D)  5 (0.1)  5 (0.0)  0.1  <0.1  <0.1  10 (0.1)  (<20.0)  8 (80.0)  Antiepileptics (N03)  642 (8.5)  987 (9.2)  307 (5.5)  834 (10.3)  488 (10.6)*  1629 (8.9)  604 (37.1)  1286 (78.9)  Other nervous system drugs (N07)  203 (2.7)  124 (1.2)  79 (1.4)  194 (2.4)  54 (1.2)*  327 (1.8)*  134 (41.0)  265 (81)  Anti-Parkinson (N04)  34 (0.4)  33 (0.3)  10 (0.2)  21 (0.3)  36 (0.8)*  67 (0.4)  14 (20.9)  62 (92.5)  Anaesthetics (N01)  17 (0.2)  9 (0.1)  13 (0.2)  <0.1  <0.1  26 (0.1)  9 (34.6)  17 (65.4)  Illegal drugs  767 (10.1)  335 (3.1)  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  527 (47.8)  778 (70.6)  Notes: For 2005 of drugs taken, drug names were recorded as unknown. For 593 of drugs recorded, the classification of unknown was attributed to them as it was not possible to attribute another ATC code based on limited information. * Statistical significance P < 0.01. Table 3 Nervous system and illegal drugs involved in IDO by gender, age, alcohol and multiple drug use, 2012–14 Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Alcohol involvement, n (%)  Multiple drug use, n (%)  Nervous system (N)  5910 (78.2)  8793 (81.7)  4332 (77.1)  6592 (81.2)  3779 (82.2)*  14 703 (80.2)*  6186 (42.1)  8095 (55.1)  Psycholeptics (N05)  3521 (46.6)  4336 (40.3)  1682 (29.9)  3830 (47.2)  2345 (51.0)*  7857 (42.9)*  3568 (45.4)  5185 (66.0)      Anxiolytics (N05B)  1832 (24.2)  2062 (19.2)  888 (15.8)  1963 (24.2)  1043 (22.7)*  3894 (21.2)*  1920 (49.3)  2677 (68.7)      Hypnotics and sedatives (N05C)  1610 (21.3)  2248 (20.9)  694 (12.4)  1836 (22.6)  1328 (28.9)*  3858 (21.0)  1736 (45.0)  2765 (71.7)      Antipsychotics (N05A)  769 (10.2)  1036 (9.6)  367 (6.5)  927 (11.4)  511 (11.1)*  1805 (9.8)  588 (32.6)  1441 (79.8)  Analgesics (N02)  2020 (26.7)  3923 (36.4)  2240 (39.9)  2392 (29.5)  1311 (28.5)*  5943 (32.4)*  2186 (36.8)  3515 (59.1)      Other analgesics and antipyretics (N02B)  1745 (23.1)  3576 (33.2)  2099 (37.4)  2069 (25.5)  1153 (25.1)*  5321 (29.0)*  1931 (36.3)  3082 (57.9)      Opioids (N02A)  342 (4.5)  484 (4.5)  206 (3.7)  420 (5.2)  200 (4.4)*  826 (4.5)  335 (40.6)  643 (77.8)      Antimigraine preparations (N02C)  <0.1  <0.1  <0.1  <0.1  <0.1  18 (0.1)  (<17.0)  17 (94.4)  Psychoanaleptics (N06)  1476 (19.5)  2604 (24.2)  1037 (18.5)  1900 (23.4)  1143 (24.9)*  4080 (22.3)*  1820 (44.6)  2991 (73.3)      Antidepressants (N06A)  1442 (19.1)  2570 (23.9)  991 (17.6)  1886 (23.2)  1135 (24.7)*  4012 (21.9)*  1804 (45.0)  2956 (73.7)      Psychostimulants, agents used for ADHD and nootropics (N06B)  34 (0.4)  41 (0.4)  51 (0.9)  17 (0.2)  7 (0.2)*  75 (0.4)  20 (26.7)  44 (58.7)      Anti-dementia drugs (N06D)  5 (0.1)  5 (0.0)  0.1  <0.1  <0.1  10 (0.1)  (<20.0)  8 (80.0)  Antiepileptics (N03)  642 (8.5)  987 (9.2)  307 (5.5)  834 (10.3)  488 (10.6)*  1629 (8.9)  604 (37.1)  1286 (78.9)  Other nervous system drugs (N07)  203 (2.7)  124 (1.2)  79 (1.4)  194 (2.4)  54 (1.2)*  327 (1.8)*  134 (41.0)  265 (81)  Anti-Parkinson (N04)  34 (0.4)  33 (0.3)  10 (0.2)  21 (0.3)  36 (0.8)*  67 (0.4)  14 (20.9)  62 (92.5)  Anaesthetics (N01)  17 (0.2)  9 (0.1)  13 (0.2)  <0.1  <0.1  26 (0.1)  9 (34.6)  17 (65.4)  Illegal drugs  767 (10.1)  335 (3.1)  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  527 (47.8)  778 (70.6)  Drug class (ATC)  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Alcohol involvement, n (%)  Multiple drug use, n (%)  Nervous system (N)  5910 (78.2)  8793 (81.7)  4332 (77.1)  6592 (81.2)  3779 (82.2)*  14 703 (80.2)*  6186 (42.1)  8095 (55.1)  Psycholeptics (N05)  3521 (46.6)  4336 (40.3)  1682 (29.9)  3830 (47.2)  2345 (51.0)*  7857 (42.9)*  3568 (45.4)  5185 (66.0)      Anxiolytics (N05B)  1832 (24.2)  2062 (19.2)  888 (15.8)  1963 (24.2)  1043 (22.7)*  3894 (21.2)*  1920 (49.3)  2677 (68.7)      Hypnotics and sedatives (N05C)  1610 (21.3)  2248 (20.9)  694 (12.4)  1836 (22.6)  1328 (28.9)*  3858 (21.0)  1736 (45.0)  2765 (71.7)      Antipsychotics (N05A)  769 (10.2)  1036 (9.6)  367 (6.5)  927 (11.4)  511 (11.1)*  1805 (9.8)  588 (32.6)  1441 (79.8)  Analgesics (N02)  2020 (26.7)  3923 (36.4)  2240 (39.9)  2392 (29.5)  1311 (28.5)*  5943 (32.4)*  2186 (36.8)  3515 (59.1)      Other analgesics and antipyretics (N02B)  1745 (23.1)  3576 (33.2)  2099 (37.4)  2069 (25.5)  1153 (25.1)*  5321 (29.0)*  1931 (36.3)  3082 (57.9)      Opioids (N02A)  342 (4.5)  484 (4.5)  206 (3.7)  420 (5.2)  200 (4.4)*  826 (4.5)  335 (40.6)  643 (77.8)      Antimigraine preparations (N02C)  <0.1  <0.1  <0.1  <0.1  <0.1  18 (0.1)  (<17.0)  17 (94.4)  Psychoanaleptics (N06)  1476 (19.5)  2604 (24.2)  1037 (18.5)  1900 (23.4)  1143 (24.9)*  4080 (22.3)*  1820 (44.6)  2991 (73.3)      Antidepressants (N06A)  1442 (19.1)  2570 (23.9)  991 (17.6)  1886 (23.2)  1135 (24.7)*  4012 (21.9)*  1804 (45.0)  2956 (73.7)      Psychostimulants, agents used for ADHD and nootropics (N06B)  34 (0.4)  41 (0.4)  51 (0.9)  17 (0.2)  7 (0.2)*  75 (0.4)  20 (26.7)  44 (58.7)      Anti-dementia drugs (N06D)  5 (0.1)  5 (0.0)  0.1  <0.1  <0.1  10 (0.1)  (<20.0)  8 (80.0)  Antiepileptics (N03)  642 (8.5)  987 (9.2)  307 (5.5)  834 (10.3)  488 (10.6)*  1629 (8.9)  604 (37.1)  1286 (78.9)  Other nervous system drugs (N07)  203 (2.7)  124 (1.2)  79 (1.4)  194 (2.4)  54 (1.2)*  327 (1.8)*  134 (41.0)  265 (81)  Anti-Parkinson (N04)  34 (0.4)  33 (0.3)  10 (0.2)  21 (0.3)  36 (0.8)*  67 (0.4)  14 (20.9)  62 (92.5)  Anaesthetics (N01)  17 (0.2)  9 (0.1)  13 (0.2)  <0.1  <0.1  26 (0.1)  9 (34.6)  17 (65.4)  Illegal drugs  767 (10.1)  335 (3.1)  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  527 (47.8)  778 (70.6)  Notes: For 2005 of drugs taken, drug names were recorded as unknown. For 593 of drugs recorded, the classification of unknown was attributed to them as it was not possible to attribute another ATC code based on limited information. * Statistical significance P < 0.01. Table 4 Drugs frequently involved in IDO, by gender and age, 2012–14 Drug  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Paracetamols (N02BE01/51)  1644 (21.7)  3443 (32.0)*  2034 (36.2)  1996 (24.6)  1057(23.0)  5087 (27.8)*  Diazepam (N05BA01)  1093 (14.5)  1007 (9.4)*  564 (10.0)  1064 (13.1)  472 (10.3)  2100 (11.5)*  Zopiclone (N05CF01)  739 (9.8)  953 (8.9)  291 (5.2)  860 (10.6)  541 (11.8)  1692 (9.2)*  Alprazolam (N05BA12)  583 (7.7)  843 (7.8)  314 (5.6)  713 (8.8)  399 (8.7)  1426 (7.8)*  Escitalopram (N06AB10)  337 (4.5)  592 (5.5)  275 (4.9)  432 (5.3)  222 (4.8)  929 (5.1)  Zolpidem (N05CF02)  288 (3.8)  559 (5.2)*  127 (2.3)  397 (4.9)  323 (7.0)  847 (4.6)*  Pregabalin (N03AX16)  331 (4.4)  470 (4.4)  129 (2.3)  424 (5.2)  248 (5.4)  801 (4.4)*  Venlafaxine (N06AX16)  206 (2.7)  426 (4.0)*  113 (2.0)  304 (3.7)  215 (4.7)  632 (3.4)*  Flurazepam (N05CD01)  255 (3.4)  369 (3.4)  111 (2.0)  289 (3.6)  224 (4.9)  624 (3.4)*  Ibuprofen (M01AE01)  366 (4.8)  846 (7.9)*  529 (9.4)  508 (6.3)  175 (3.8)  1212 (6.6)*  Diclofenac (M01AB05)  142 (1.9)  290 (2.7)*  159 (2.8)  200 (2.5)  73 (1.6)  432 (2.4)*  Illegal drugs  767 (10.1)  335 (3.1)*  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  Drug  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Paracetamols (N02BE01/51)  1644 (21.7)  3443 (32.0)*  2034 (36.2)  1996 (24.6)  1057(23.0)  5087 (27.8)*  Diazepam (N05BA01)  1093 (14.5)  1007 (9.4)*  564 (10.0)  1064 (13.1)  472 (10.3)  2100 (11.5)*  Zopiclone (N05CF01)  739 (9.8)  953 (8.9)  291 (5.2)  860 (10.6)  541 (11.8)  1692 (9.2)*  Alprazolam (N05BA12)  583 (7.7)  843 (7.8)  314 (5.6)  713 (8.8)  399 (8.7)  1426 (7.8)*  Escitalopram (N06AB10)  337 (4.5)  592 (5.5)  275 (4.9)  432 (5.3)  222 (4.8)  929 (5.1)  Zolpidem (N05CF02)  288 (3.8)  559 (5.2)*  127 (2.3)  397 (4.9)  323 (7.0)  847 (4.6)*  Pregabalin (N03AX16)  331 (4.4)  470 (4.4)  129 (2.3)  424 (5.2)  248 (5.4)  801 (4.4)*  Venlafaxine (N06AX16)  206 (2.7)  426 (4.0)*  113 (2.0)  304 (3.7)  215 (4.7)  632 (3.4)*  Flurazepam (N05CD01)  255 (3.4)  369 (3.4)  111 (2.0)  289 (3.6)  224 (4.9)  624 (3.4)*  Ibuprofen (M01AE01)  366 (4.8)  846 (7.9)*  529 (9.4)  508 (6.3)  175 (3.8)  1212 (6.6)*  Diclofenac (M01AB05)  142 (1.9)  290 (2.7)*  159 (2.8)  200 (2.5)  73 (1.6)  432 (2.4)*  Illegal drugs  767 (10.1)  335 (3.1)*  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  * Statistical significance P < 0.01. Table 4 Drugs frequently involved in IDO, by gender and age, 2012–14 Drug  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Paracetamols (N02BE01/51)  1644 (21.7)  3443 (32.0)*  2034 (36.2)  1996 (24.6)  1057(23.0)  5087 (27.8)*  Diazepam (N05BA01)  1093 (14.5)  1007 (9.4)*  564 (10.0)  1064 (13.1)  472 (10.3)  2100 (11.5)*  Zopiclone (N05CF01)  739 (9.8)  953 (8.9)  291 (5.2)  860 (10.6)  541 (11.8)  1692 (9.2)*  Alprazolam (N05BA12)  583 (7.7)  843 (7.8)  314 (5.6)  713 (8.8)  399 (8.7)  1426 (7.8)*  Escitalopram (N06AB10)  337 (4.5)  592 (5.5)  275 (4.9)  432 (5.3)  222 (4.8)  929 (5.1)  Zolpidem (N05CF02)  288 (3.8)  559 (5.2)*  127 (2.3)  397 (4.9)  323 (7.0)  847 (4.6)*  Pregabalin (N03AX16)  331 (4.4)  470 (4.4)  129 (2.3)  424 (5.2)  248 (5.4)  801 (4.4)*  Venlafaxine (N06AX16)  206 (2.7)  426 (4.0)*  113 (2.0)  304 (3.7)  215 (4.7)  632 (3.4)*  Flurazepam (N05CD01)  255 (3.4)  369 (3.4)  111 (2.0)  289 (3.6)  224 (4.9)  624 (3.4)*  Ibuprofen (M01AE01)  366 (4.8)  846 (7.9)*  529 (9.4)  508 (6.3)  175 (3.8)  1212 (6.6)*  Diclofenac (M01AB05)  142 (1.9)  290 (2.7)*  159 (2.8)  200 (2.5)  73 (1.6)  432 (2.4)*  Illegal drugs  767 (10.1)  335 (3.1)*  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  Drug  Male, n (%) N = 7562  Female, n (%) N = 10 767  <25 years, n (%) N = 5618  25–44 years, n (%) N = 8115  45+years, n (%) N = 4596  Total, n (%) N = 18 329  Paracetamols (N02BE01/51)  1644 (21.7)  3443 (32.0)*  2034 (36.2)  1996 (24.6)  1057(23.0)  5087 (27.8)*  Diazepam (N05BA01)  1093 (14.5)  1007 (9.4)*  564 (10.0)  1064 (13.1)  472 (10.3)  2100 (11.5)*  Zopiclone (N05CF01)  739 (9.8)  953 (8.9)  291 (5.2)  860 (10.6)  541 (11.8)  1692 (9.2)*  Alprazolam (N05BA12)  583 (7.7)  843 (7.8)  314 (5.6)  713 (8.8)  399 (8.7)  1426 (7.8)*  Escitalopram (N06AB10)  337 (4.5)  592 (5.5)  275 (4.9)  432 (5.3)  222 (4.8)  929 (5.1)  Zolpidem (N05CF02)  288 (3.8)  559 (5.2)*  127 (2.3)  397 (4.9)  323 (7.0)  847 (4.6)*  Pregabalin (N03AX16)  331 (4.4)  470 (4.4)  129 (2.3)  424 (5.2)  248 (5.4)  801 (4.4)*  Venlafaxine (N06AX16)  206 (2.7)  426 (4.0)*  113 (2.0)  304 (3.7)  215 (4.7)  632 (3.4)*  Flurazepam (N05CD01)  255 (3.4)  369 (3.4)  111 (2.0)  289 (3.6)  224 (4.9)  624 (3.4)*  Ibuprofen (M01AE01)  366 (4.8)  846 (7.9)*  529 (9.4)  508 (6.3)  175 (3.8)  1212 (6.6)*  Diclofenac (M01AB05)  142 (1.9)  290 (2.7)*  159 (2.8)  200 (2.5)  73 (1.6)  432 (2.4)*  Illegal drugs  767 (10.1)  335 (3.1)*  427 (7.6)  630 (7.8)  45 (1.0)  1102 (6.0)*  * Statistical significance P < 0.01. Drugs most frequently involved in IDO Table 4 illustrates the individual drugs most frequently taken in IDO. Five of these are benzodiazepine derivatives and other related drugs (diazepam, zopiclone, alprazolam, zolpidem and flurazepam), cumulatively involved in 31.1% of presentations. The most frequently used drug was paracetamol, involved in 27.8% of IDOs. Anti-inflammatory drugs ibuprofen and diclofenac, and antidepressant drugs escitalopram and venlafaxine were also frequently taken in IDO (6.6%, 2.4%, 5.1% and 3.4%). Gender and age differences Significant gender differences were found in relation to drugs involved in IDO. Musculoskeletal system drugs were significantly more common in female compared with male IDOs (14.0% vs. 9.2%, x2=94.34, df = 1, P < 0.01). Similarly, IDO involving analgesics and antidepressants were significantly more common in female presentations (36.4% vs. 26.7%, x2=191.65, df = 1, P < 0.01 and 23.9% vs. 19.1%, x2=59.865, df = 1, P < 0.01) (table 3). In particular paracetamol was involved significantly more often in female IDOs (32.0% vs. 21.7%, x2=232.16, df = 1, P < 0.01). Illegal drugs were three times more common in male compared with female presentations (10.1% vs. 3.1%, x2 = 388.66, df = 1, P < 0.01) (table 2). Similarly, anxiolytic drugs were also taken significantly more frequently by males (24.2% vs. 19.2%, x2=68.388, df = 1, P < 0.01). Regarding age, those under 25 years took analgesic drugs more frequently than those within the older age groups (39.9%, x2=206.30, df = 2, P < 0.01). Paracetamol overdose was highest among persons under 25 years (36.2%, x2=292.30, df = 2, P < 0.01) and was present in 43.8% of IDOs by females aged under 25 years. Benzodiazepine involvement increased with age and was highest for those aged 45 years and over (44.3%, x2=502.16, df = 2, P < 0.01). Antidepressants were involved most commonly among those aged 45 years and over (24.7%, x2=89.17, df = 2, P < 0.01). Hypnotics and sedative use in IDO was significantly higher among those aged 45 years and over (28.9%, x2=438.00, df = 2, P < 0.01), and involved mainly sleeping sedatives zopiclone, zolpidem and flurazepam (9.2%, 4.6% and 3.4%). Alcohol involvement Alcohol involvement in IDO was significantly higher in male compared with female presentations (44.7% vs. 37.8%, x2=86.82, df = 1, P < 0.01). Alcohol was most frequently consumed in presentations involving illegal drugs (47.8%) followed by anxiolytics (49.3%, x2=154.52, df = 1, P < 0.01) (table 3). Multiple vs. single drug use As described in table 1 presentations made by those aged 15–24 years had the highest proportion of multiple drug use when compared with other age groups (26.3%, x2=74.55, df = 5, P < 0.01). The median number of tablets taken was considerably higher in multiple drug use at 27 (IQR 15–45) compared with a median of 18 (IQR 10–30) in single drug use (t = 25.112, P < 0.01). Of those who engaged in multiple drug use 59.5% took more than 20 tablets in their IDO presentation compared with 42.3% of those who engaged in single drug use (t = 9.059, P < 0.01). Discussion Key findings This is the first national study to descriptively profile IDO. The present study utilized a national self-harm surveillance system to describe the clinical and socio-demographic profile of persons engaging in IDO, to identify drugs used in overdose and to quantify the frequency of alcohol involvement and multiple drug use. We found that individuals engaging in IDO were most often female and young to middle aged. Alcohol use was particularly associated with being male and over 35 years, taken most often in presentations involving anxiolytics and illegal drugs. Multiple drug use was frequent; not gender-specific; most common in IDOs enacted by young-middle aged individuals, and associated with the consumption of greater quantities of tablets in overdose. Analgesic, antidepressant, anxiolytic and hypnotic and sedative drugs were most commonly consumed in IDO with age, gender, alcohol involvement and multiple drug use significantly impacting the frequency of their involvement. We found paracetamol to be the most frequently used drug, with a concerning proportion of young females overdosing with the drug. Building on existing literature The demographic profile of persons engaging in IDO identified by the present study is similar to that previously described.9,16,17 The involvement of alcohol combined with IDO was similar to some existing findings,6,10,17 particularly in relation to its concentration among persons aged 35–54 years.25 However, it was lower than that recently recorded by the Multicentre Self-Harm study (41% vs. 58%)8 and the Northern Ireland Registry of Self-Harm (59%).1 Our findings also quantify and elucidate multiple drug use in IDO, which was more frequent than that reported by Finkelstein et al.9 in Canada and Vancayseele et al.17 in Belgium (26% and 18%). As expected, multiple drug use was associated with higher quantities of tablets taken in overdose, which has been correlated with repeat self-harm and an increased risk of suicide.26 Our findings detailing the types of drugs used in IDO build upon those reported by Griffin et al.,1 owing to the application of ATC categorization to our data, facilitating the comprehensive identification of drugs used in IDO. The involvement of benzodiazepines in IDO was substantially higher in our study compared with their frequency as reported by the Multicentre study (36% vs. 14%).6,16 This more frequent use of benzodiazepines in IDO signals an association between these drugs and high risk of self-harm, potentially due to differences in the accessibility of these drugs, the most notable and worthy of further research would be disparities in prescribing patterns. Analgesic use in IDO in Ireland remains proportionately lower than in England (32.4% vs. 45.7%),16 which is potentially impacted by differences in access to paracetamol. In England quantities of paracetamol which can be purchased over-the-counter in pharmacy and non-pharmacy outlets exceed those available in Ireland.27 Disparities in relation to adherence to sales restriction legislation for paracetamol have been reported,28,29 with comparable research into adherence to sales restrictions in pharmacies required. This study too identifies the concerning use of paracetamol in IDO, with variations in its involvement determined by gender and age, as per previous research.17,30 Clinical and research implications The findings of this study provide detailed insights into the frequent use of prescription, sale-restricted and illegal drugs in IDO. We have identified populations at risk of taking prescription only drugs in IDO, a finding which can inform prescribing guidelines, in particular to those at risk of self-harm. New insights into the involvement of the range of drugs used in IDO highlights the need for physicians to also consider risk when prescribing for the management of mental and physical conditions. In line with evidence-based suicide prevention initiatives, physicians may benefit from additional training regarding the frequent use of particular drugs in IDO and measures to address issues with prescribing.31,32 Furthermore, the commonality of multiple drug use in our sample and the association between this and repeat self-harm and suicide,26 underlines the need to monitor the availability of multiple drug types to individuals, via prescription review, particularly to those at risk of self-harm. Means restriction has proven efficacy in relation to IDO27,32–37 and is increasingly recommended by national suicide prevention and drug strategies.38,39 The frequent use of over-the-counter and restricted-sale drugs found in this study accompanied by identified issues with adherence to paracetamol sales-restrictions28,29 highlight the need to review the operations of existing legislation and to examine new ways of preventing individuals, particular young people, from accessing excessive quantities of drugs. Considering alcohol, the specialized care needs of patients who have engaged in IDO with alcohol will require specialist training for hospital staff in the management of these patients.10 Strengths and limitations In this study, we used robust data from a national self-harm registry that is internationally exclusive to this field. The use of this national data set with full geographic coverage is unique, as endorsed by the World Health Organization.32,40 The application of the ATC classification system22 to our data is progressive as it has enabled the comprehensive examination of specific drugs taken in IDO, previously restricted by unstandardized methods of classification.1,13 Furthermore, this system presents considerable potential to facilitate comparative work with other drug utilization statistics and data sets between countries and across healthcare settings. There are a number of limitations to this study. Information collected on drugs used in IDO was self-reported. Several of the reported drugs taken in IDO may be used to treat a range of indications, therefore, we cannot directly attribute these drugs to particular disorders or make associations between certain conditions and risk of IDO. Information on the drug dosage and source, including whether or not it was prescribed to the individual is not currently collected. Conclusion This study presents a comprehensive profile of individuals presenting to hospital following IDO with respect to gender, age, alcohol involvement and multiple drug use. The findings raise important concerns regarding the use of specific prescribed drugs and patient safety which should be considered in prescribing guidelines. The frequent use of over-the-counter drugs raises concerns about adherence to and enforcement of legislation regulating the sale of certain drugs. The obligation to concurrently and effectively address the specialized care needs of IDO patients with alcohol intoxication is reiterated by our findings, requiring address in terms of resources and training. Acknowledgements The National Self-Harm Registry, Ireland is funded by the Health Service Executive’s National Office for Suicide Prevention. We thank the data registration officers for the work collecting information on self-harm presentations to hospitals across Ireland. We also thank Mr Eoin Perry who diligently assisted on data coding at the early stages of this research paper. Funding Funding for this research is provided collaboratively by the University of Manchester and the National Suicide Research Foundation, Cork, Ireland, which is in receipt of funding from the Irish Health Service Executive's National Office for Suicide Prevention. Conflicts of interest: None declared. Key points Frequently used drugs, alcohol and multiple drug use in intentional overdose are examined using a national data set. Analgesics, antidepressants, anxiolytics and hypnotic and sedatives are the most frequent drug groups taken in overdose. Paracetamol is the most common drug taken in overdose, particularly among females and those under 25 years. 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The European Journal of Public HealthOxford University Press

Published: Mar 12, 2018

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