- Research article
- Open Access
Evaluation of factors related to overdose in patients with impaired consciousness who are transported by emergency medical services: an age-specific research
Journal of Pharmaceutical Health Care and Sciences volume 7, Article number: 34 (2021)
Drug overdose accounts for most of the admissions to the emergency department. Prescription drugs, most of which are psychotropic medications, are often misused for drug overdose. The purpose of this study was to investigate the association between overdose in patients transported with disorders of consciousness and psychotropic medications administered prior to transport, so as to enable quick differentiation of drug overdose patients from patients with disorders of consciousness.
We evaluated 222 patients transported to the Advanced Critical Care Center of Teikyo University Hospital due to disorders of consciousness. The patients were categorized into two groups: overdose group (n = 128) and control group with other disorders of consciousness (n = 94). Logistic regression models were used to assess the association between disorders of consciousness due to drug overdose and psychotropic drugs prescribed before emergency transportation based on sex and age.
According to multivariate logistic regression analysis, only female sex (odds ratio [OR] 4.54, 95% confidence interval [CI] 2.43–8.05, P < 0.0001) was associated with overall overdose. Results from the univariate logistic regression analysis showed that in the group of patients aged 40–50 years, female sex (OR 4.36, 95% CI; 1.54–12.4, P = 0.006) and the use of psychotropic drugs (OR 5.05, 95% CI; 1.75–14.6, P = 0.003), benzodiazepines (OR 4.64, 95% CI; 1.61–13.4, P < 0.05), antidepressants (OR 11.4, 95% CI; 2.35–55.8, P = 0.003), and anticonvulsants (OR 4.46, 95% CI; 1.11–17.9, P = 0.035) were associated with overdose. According to multivariate logistic regression analysis, female sex (OR 4.44, 95% CI; 1.37–14.3, P = 0.013) and antidepressants (OR 7.95, 95% CI; 1.21–52.1, P = 0.031) were associated with overdose patients aged 40–50 years.
As a reference in distinguishing overdose in women in their 40s and 50s who present with impaired consciousness, attention may need to be paid to the type of psychotropic drug used, especially antidepressants.
Drug overdose is the excessive use of drugs, resulting in acute and deleterious effects on the body or psyche, and is one of the major causes of emergency transportation of patients [1,2,3]. The drugs prescribed by physicians, especially psychotropic drugs, such as benzodiazepine receptor agonists (BZs) and antidepressants [4,5,6], are misused by these patients for drug overdose. In addition, more than 75% of these cases include those who intentionally overdose for suicidal purposes rather than accidental overdose [6, 7].
BZs have been reported to be the most common psychotropic drugs with a tendency for overdose  and are associated with an increased risk of suicide [9,10,11]. Furthermore, it has been reported that as with abuse of illegal drugs, such as stimulants, the use of BZs is associated with certain patient characteristics, including younger age and female sex . In addition, significant increases in the prevalence of BZ exposure and overdose have been observed, especially in children . In other reports, acute BZ intoxication and accidental overdose have been reported in elderly people [14,15,16]. Furthermore, some studies have reported that antidepressants are more commonly used for intentional drug overdose in women than in men [17,18,19]. Depression is a common risk factor associated with more than half of suicidal deaths . Therefore, treatment of depression is often a target of suicide prevention efforts. Furthermore, there are reports of iatrogenic suicidal effects of antidepressants [21, 22] as well as the potential lethality of antidepressant overdose .
Disorders of consciousness are frequently encountered symptoms in the emergency department, and sudden disorders of consciousness are often caused by brain or heart angiopathy, arrhythmias, and seizures, or from life-threatening infections of the lungs and liver as well as drug-induced dysfunction of organs, such as the kidneys. For differential diagnosis of overdose, there is a need to exclude other diseases that disturb consciousness (in order). Therefore, it may take some time to confirm a diagnosis as an overdose. There is therefore the need for prompt identification of overdose patients and subsequent identification of the responsible drugs. Identifying the responsible drug may help determine the severity of overdose and to determine the availability of antagonists. Intentional drug overdose is the most common method of self-harm. As psychiatric disorders are common in self-harm patients, the medication used to treat these disorders can become the means for the self-harm act. Therefore, this study focused on the administration of physician-prescribed medications before emergency transportation. Information regarding medicines prescribed before emergency transportation can be obtained at the time of transportation from the medical emergency personnel or from the patients’ families.
Although there are studies investigating the prescription status of psychotropic drugs before emergency transportation [12,13,14,15,16,17,18,19], few studies have focused on patients with disorders of consciousness. Moreover, as the potential risks associated with psychotropic drug overdose are known to be diverse depending on gender and age [12,13,14,15,16,17,18,19], it has been difficult to identify specific risks associated with overdose during emergency transport in patients with disorders of consciousness.
In this study, we investigated the association between drug overdose in transported patients with consciousness disorders and psychotropic medications (especially BZs and antidepressant drugs) administered before emergency transportation. Since the backgrounds differ depending on the age group, we investigated whether the types of related psychotropic drugs differed depending on the age group.
Patients and patient data
The study investigated a total of 222 patients diagnosed with disorder of consciousness, who had been transported to the Emergency and Critical Care Center of Teikyo University Hospital from October 19, 2016, to December 20, 2017 (Table 1). Of these, patients who were finally diagnosed with overdose by their doctors were defined as “overdose” patients. The patients were divided into an “overdose” group (n = 128) and “other consciousness disorders” group (n = 94). Overdose patients were further divided into three groups, according to age: ≤39 years (n = 72), 40–59 years (n = 34), and ≥ 60 years (n = 22). Similarly, patients with other consciousness disorders who were included in the control group were further divided into three groups, according to age: ≤39 years (n = 28), 40–59 years (n = 31), and ≥ 60 years (n = 35).
Patient data were retrieved from the electronic medical records. The research data comprised age, sex, medical history (medical department and disorder), outcome, and prescribed drugs. In all patients, an investigation of prescribed drugs was conducted for all drugs within the range described in the electronic medical record. Patients with pesticide poisoning, detergent poisoning, narcotic poisoning, and psychostimulant poisoning were excluded from the study. Psychiatric disorders were further investigated according to the International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10) in a medical history survey. Based on the information available in medication notebooks and electronic medical records of interviews with patients and families, the drugs that had apparently been prescribed before arrival in the emergency room were tabulated as prescribed drugs. Anticonvulsants included sodium valproate, lamotrigine, and carbamazepine.
Logistic regression analysis was performed using the JMP Pro. 13 (SAS Institute Inc., Cary, NC, USA). The significance level was set at P < 0.05.
Characteristics of patients prescribed drugs for overdose
The average age of patients in the overdose group was 40.6 years (control: 51.9 years), and the number of women was more than twice that of men (Table 1). Nearly 80% of overdose patients had a history of psychiatric consultation, of which the most common psychiatric disorders were F3 (mood [affective] disorders), followed by F4 (neurotic, stress-related, and somatoform disorders), and F2 (schizophrenia, schizotypal, and delusional disorders) (Table 1). As for the outcome, more than 80% (107/128, control 57/94 60.6%) of the patients returned home early without hospitalization (Tables 1). The characteristics of prescribed psychotropic drugs in overdose patients were examined. As shown in Table 2, univariate analysis revealed that female sex (odds ratio [OR] 5.08, 95% confidence interval [CI] 2.9–9.1, P < 0.00001), psychotropic drugs (OR 4.11, 95% CI 2.34–7.24, P < 0.0001), BZs (OR 3.09, 95% CI 1.75–5.45, P < 0.0001), antidepressant drugs (OR 3.82, 95% CI 1.80–8.12, P = 0.0005), antipsychotic drugs (OR 3.31, 95% CI 1.76–6.22, P = 0.0002), lithium carbonate (OR 10.5, 95% CI 1.35–81.8, P = 0.0247), and anticonvulsants (OR 4.30, 95% CI 1.70–10.8, P = 0.002) were significantly correlated with overdose. According to multivariate logistic regression analysis (Table 2), female sex (OR 4.54, 95% CI 2.43–8.05, P < 0.0001) was associated with overall overdose.
Age-specific analysis of prescribed psychotropic drugs for overdose
To examine the characteristics of prescribed psychotropic drugs by age group, we classified the patients into three age groups: ≤39 years, 40–59 years, and ≥ 60 years (Table 3). As shown in Table 3, univariate analysis revealed that BZs (OR 4.64, 95% CI 1.61–13.4, P = 0.005) and antidepressant drugs (OR 11.4, 95% CI 2.35–55.8, P = 0.003) were significantly correlated with overdose. However, antipsychotic drugs did not significantly correlate with overdose in the 40–59 years age group. In contrast, the use of BZs, antidepressant drugs, and antipsychotic drugs was not significantly different in the ≤39 years and ≥ 60 age groups. Data of patients prescribed lithium carbonate were unsuitable for analysis owing to small sample size. Anticonvulsants were associated with overdose in the 40–59 years age group (Table 4), while data of patients in the ≤39 years and ≥ 60 years age groups were unsuitable for analysis owing to small sample size.
Analysis of overdose in patients in the 40–59 years age group
According to univariate logistic regression analysis (Table 4), female sex (OR 4.36, 95% CI; 1.54–12.4, P = 0.006), psychotropic drugs (OR 5.05, 95% CI; 1.75–14.6, P = 0.003), BZs (OR 4.64, 95% CI; 1.61–13.4, P < 0.05), antidepressants (OR 11.4, 95% CI; 2.35–55.8, P = 0.003), and anticonvulsants (OR 4.46, 95% CI; 1.11–17.9, P = 0.035) were associated with overdose in patients in the 40–59 years age group.
Sex, BZs, and antidepressant drugs are known to be associated with overdose [1, 3]. In this analysis, female sex, BZs, and antidepressant drugs were selected for multivariate logistic analysis, finding that female sex (OR 4.44, 95% CI; 1.37–14.3, P = 0.013) and antidepressant drugs (OR 7.95, 95% CI; 1.21–52.1, P = 0.031) were associated with overdose in patients in the 40–59 years age group (Table 4).
In this study, we investigated the association between drug overdose in transported patients with consciousness disorders and psychotropic medications (especially BZs and antidepressant drugs, which have been reported to have different potential risk profiles depending on age) administered before emergency transportation. All prescription drugs in the subjects were analyzed, but only analysis of psychotropic drugs provided significant results in line with the objectives of this study; therefore, we focused on psychotropic medications. Multivariate analysis of overall age showed that female sex was associated with drug overdose in disorders of consciousness, and no other categories of psychotropic medications were found to be associated with drug overdose. Age-specific logistic analysis of BZs, antidepressants, and antiepileptic drugs showed that the use of BZs and antidepressants in patients aged 40–59 years was associated with disorders of consciousness due to drug overdose. Multivariate analysis of data of patients in the 40–59 years age group showed that female sex and use of antidepressants were associated with consciousness disorders due to overdose.
In this study, female sex was associated with drug overdose for all age groups. This finding is in line with those of the previous studies in which there were a greater number of females with overdose of psychotropic drugs and there was a higher suicide rate due to drug overdose in females, although males had a higher suicide rate and recurrence rate . Furthermore, it has been reported that overdose of psychotropic drugs is associated with the prescription of psychotropic drugs before emergency transportation, with BZs accounting for 65% of prescriptions before transportation . In addition, an increase in the odds of using antidepressants and antipsychotics in episodes of suicide was observed when the rate of prescription increased . In this study, prescription of BZs, antipsychotics, and antidepressants was confirmed in patients with disorders of consciousness due to overdose. This finding was in agreement with the above results, although there were differences in the aggregation method.
Multivariate analysis of data of patients in the 40–59 years age group showed that female sex and use of antidepressants were associated with disorders of consciousness due to overdose, although there was no association with BZs. Previous studies have reported that antidepressants are significantly more commonly used for intentional drug overdose among women than among men [17,18,19]. In addition, regarding age dependency of the comparison of the rates of suicide attempts after and before the start of treatment with antidepressants, it was reported that the highest rates of suicide were observed among those > 40 years during the first month . In this study, among overdose patients, there was a high proportion of F3 in patients with depression. Depression is also known to be the main clinical manifestation of menopause and often occurs in females aged 45–55 years. Previous studies have shown that in menopausal women, 50–60% have mild depression and 1–3% suffer from severe depression, among which about 15% have suicidal behavior . Furthermore, with an increase in the use of antidepressants due to the onset of depression in menopause, it can be assumed that the risk of antidepressant use has increased in females in the 40–59 years age group.
BZs are widely prescribed in general clinical departments as well as for patients with psychiatric disorders, including children and the elderly . A survey on BZ prescriptions indicated that 54% of the prescriptions, including BZs, were from departments other than psychiatry, and 33.8% were for patients over 65 years old . Prescriptions for elderly patients from the psychiatry department were less frequent than those from other departments. In our study, BZs had lower odds than antidepressants according to multivariate analysis. The reason for this is that BZs are widely prescribed in general clinical departments other than psychiatry for sleep disorders. In this study, the proportions of overdose patients and other patients with impaired consciousness who visited the general clinical department were 58.3 and 64.3%, respectively, in the 40–59 years age group, and no significant difference was observed between the two groups. Therefore, the odds ratio of BZs may not have been as high as that of antidepressants in the 40–59 years age group.
Based on the results of this research, it is better to proactively identify drugs brought to the emergency outpatient department and to link them to research results, such as shortening the time required to diagnose the cause of consciousness disorders compared to before initiating response. Moreover, in terms of clinical practice, this study’s logistic analysis results may potentially indicate what should be noted when managing a patient’s medication. To prevent overdose, psychotropic drug optimization may be needed in patients in their 40–50s, although larger validation studies are needed.
The limitation of this study is that information on the time and period of prescription and prescription amount of each psychotropic drug was not available. Since the purpose of this study was to obtain an index from the information during emergency transportation of patients, we collected data regarding the presence or absence of prescription drugs during emergency transportation. In addition, owing to the small number of cases, it was not possible to classify and analyze antidepressants, such as tricyclic antidepressants, tetracyclic antidepressants, and selective serotonin reuptake inhibitors. In the future, we would like to increase the number of cases to determine the other highly relevant antidepressants.
In this study, we were able to identify factors related to drug overdose in patients with disorders of consciousness depending on age. As a reference in distinguishing overdose in women in their 40s and 50s who present with impaired consciousness, attention may need to be paid to the type of psychotropic drug used, especially antidepressants.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Okumura Y, Shimizu S, Ishikawa KB, Matsuda S, Fushimi K, Ito H. Comparison of emergency hospital admissions for drug poisoning and major diseases: a retrospective observational study using a nationwide administrative discharge database. BMJ Open. 2012b;2(6):e001857. https://doi.org/10.1136/bmjopen-2012-001857.
Schwake L, Wollenschläger I, Stremmel W, Encke J. Adverse drug reactions and deliberate self-poisoning as cause of admission to the intensive care unit: a 1-year prospective observational cohort study. Intensive Care Med. 2009;35(2):266–74. https://doi.org/10.1007/s00134-008-1250-1.
Ichikura K, Okumura Y, Takeuchi T. Associations of adverse clinical course and ingested substances among patients with deliberate drug poisoning: a cohort study from an intensive care unit in Japan. PLoS One. 2016;11(8):e0161996. https://doi.org/10.1371/journal.pone.0161996.
Sarchiapone M, Mandelli L, Iosue M, Andrisano C, Roy A. Controlling access to suicide means. Int J Environ Res Public Health. 2011;8(12):4550–62. https://doi.org/10.3390/ijerph8124550.
Xiang Y, Zhao W, Xiang H, Smith GA. ED visits for drug–related poisoning in the United States, 2007. Am J Emerg Med. 2012;30(2):293–301. https://doi.org/10.1016/j.ajem.2010.11.031.
Hirata K, Matsumoto Y, Tomioka J, Kurokawa A, Matsumoto M, Murata M. Acute drug poisoning at critical care departments in Japan. Japanese J Hospital Pharmacy. 1998;24(4):340–8. https://doi.org/10.5649/jjphcs1975.24.340.
Hovda KE, Bjornaas MA, Skog K, Opdahl A, Drottning P, Ekeberg O, et al. Acute poisonings treated in hospitals in Oslo: a one–year prospective study (I): pattern of poisoning. Clin Toxicol Phila. 2008;46(1):35–41. https://doi.org/10.1080/15563650601185969.
Okumura Y, Sakata N, Takahashi K, Nishi D, Tachimori H. Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: an exploratory descriptive study using a nationwide claims database. J Epidemiol. 2017;27(8):373–80. https://doi.org/10.1016/j.je.2016.08.010.
Dodds TJ. Prescribed benzodiazepines and suicide risk: a review of the literature. Prim Care Companion CNS Disord. 2017;19(2):16r02037.
Brown TL, Gutierrez PM, Grunwald GK, DiGuiseppi C, Valuck RJ, Anderson HD. Access to psychotropic medication via prescription is associated with choice of psychotropic medication as suicide method: A retrospective study of 27,876 suicide attempts. J Clin Psychiatry. 2018;79:17m11982. https://doi.org/10.4088/JCP.17m11982.
Haoka T, Sakata N, Okamoto H, Oshiro A, Shimizu T, Naito Y, et al. Intentional or unintentional drug poisoning in elderly people: retrospective observational study in a tertiary care hospital in Japan. Acute Med Surg. 2019;6(3):252–8. https://doi.org/10.1002/ams2.403.
Matsumoto T, Usami T, Funeta D, Murakami M, Tanibuchi Y. http://ncnp.go.jp/nimh/yakubutsu/report/pdf/J_NMHS_2018.pdf. Accessed 13 Oct 2020.
Friedrich JM, Sun C, Geng X, Calello DP, Gillam M, Medeiros KL, et al. Child and adolescent benzodiazepine exposure and overdose in the United States: 16 years of poison center data. Clin Toxicol (Phila). 2020;58:725–31.
Piekarska-Wijatkowska A, Kobza-Sindlewska K, Rogaczewska A, Zajdel R, Krakowiak A. Intentional poisoning among elderly people-residents of a large urban agglomeration in Poland. Hum Exp Toxicol. 2016;35(12):1328–36. https://doi.org/10.1177/0960327116630353.
Carlsten A, Waern M, Holmgren P, Allebeck P. The role of benzodiazepines in elderly suicides. Scand J Public Health. 2003;31(3):224–8. https://doi.org/10.1080/14034940210167966.
Vukcević NP, Ercegović GV, Segrt Z, Djordjević S, Stosić JJ. Benzodiazepine poisoning in elderly. Vojnosanit Pregl. 2016;73(3):234–8. https://doi.org/10.2298/VSP141208025P.
Vancayseele N, Rotsaert I, van Heeringen GPK. Medication used in intentional drug overdose in Flanders 2008–2013. PLoS One. 2019;14(5):e0216317. https://doi.org/10.1371/journal.pone.0216317.eCollection.
Townsend E, Hawton K, Harriss L, Bale E, Bond A. Substances used in deliberate self–poisoning 1985–1997: trends and associations with age, gender, repetition and suicide intent. Soc Psychiatry Psychiatr Epidemiol. 2001;36(5):228–34. https://doi.org/10.1007/s001270170053.
Tournier M, Grolleau A, Cougnard A, Molimard M, Verdoux H. Factors associated with choice of psychotropic drugs used for intentional drug overdose. Eur Arch Psychiatry Clin Neurosci. 2009;259(2):86–91. https://doi.org/10.1007/s00406-008-0839-2.
Cavanagh JT, Carson AJ, Sharpe M, Lawrie SM. Psychological autopsy studies of suicide: a systematic review. Psychol Med. 2003;33(3):395–405. https://doi.org/10.1017/S0033291702006943.
Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry. 2006;63(3):332–9. https://doi.org/10.1001/archpsyc.63.3.332.
Juurlink DN, Mamdani MM, Kopp A, Redelmeier DA. The risk of suicide with selective serotonin reuptake inhibitors in the elderly. Am J Psychiatry. 2006;163(5):813–21. https://doi.org/10.1176/ajp.2006.163.5.813.
Hawton K, Bergen H, Simkin S, Cooper J, Waters K, Gunnell D, et al. Toxicity of antidepressants: rates of suicide relative to prescribing and non–fatal overdose. Br J Psychiatry. 2010;196(5):354–8. https://doi.org/10.1192/bjp.bp.109.070219.
Okumura Y, Tachimori H, Matsumoto T, Nishi D. Exposure to psychotropic medications prior to overdose: a case–control study. Psychopharmacology. 2015;232(16):3101–9. https://doi.org/10.1007/s00213-015-3952-8.
Termorshuizen F, Palmen SJM, Heerdink ER. Suicide behavior before and after the start with antidepressants: A high persistent risk in the first month of treatment among the Young. Int J Neuropsychopharmacol. 2016;19:pyv081. https://doi.org/10.1093/ijnp/pyv081.
Huang H, Zhao J, Jiang L, Xie Y, Xia Y, Lv R, et al. Paeoniflorin improves menopause depression in ovariectomized rats under chronic unpredictable mild stress. Int J Clin Exp Med. 2015;8:5103–11.
Nakajima M, Homma M, Igarashi T, Kambayashi Y, Ohara M, Nagasawa I, et al. Survey on benzodiazepine prescriptions. Jpn J Pharmaceutical Health Care Sci. 2010;36:863–7.
There are no funding sources for this manuscript.
Ethics approval and consent to participate
This study was conducted after a review by the Teikyo University Ethical Review Board for Medical and Health Research Involving Human Subjects in accordance with the ethics guidelines for medical research on humans (approval number: 19–049).
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Nagashima, K., Sumida, M., Imanaka, S. et al. Evaluation of factors related to overdose in patients with impaired consciousness who are transported by emergency medical services: an age-specific research. J Pharm Health Care Sci 7, 34 (2021). https://doi.org/10.1186/s40780-021-00217-8
- Drug overdose
- Psychotropic drug
- Disorder of consciousness