Characteristics of hospital-treated intentional drug overdose in Ireland and Northern Ireland

OBJECTIVES This study compared the profile of intentional drug overdoses (IDOs) presenting to emergency departments in Ireland and in the Western Trust Area of Northern Ireland between 2007 and 2012. Specifically the study aimed to compare characteristics of the patients involved, to explore the factors associated with repeated IDO and to report the prescription rates of common drug types in the population. METHODS We utilised data from two comparable registries which monitor the incidence of hospital-treated self-harm, recording data from deliberate self-harm presentations involving an IDO to all hospital emergency departments for the period 1 January 2007 to 31 December 2012. RESULTS Between 2007 and 2012 the registries recorded 56,494 self-harm presentations involving an IDO. The study showed that hospital-treated IDO was almost twice as common in Northern Ireland than in Ireland (278 vs 156/100,000, respectively). CONCLUSIONS Despite the overall difference in the rates of IDO, the profile of such presentations was remarkably similar in both countries. Minor tranquillisers were the drugs most commonly involved in IDOs. National campaigns are required to address the availability and misuse of minor tranquillisers, both prescribed and non-prescribed.

Use of analgesics in intentional drug overdose presentations to hospital before and after the withdrawal of distalgesic from the Irish market

BACKGROUND: Distalgesic, the prescription-only analgesic compound of paracetamol (325 mg) and dextropropoxyphene (32.5 mg) known as co-proxamol in the UK, was withdrawn from the Irish market as of January 2006. This study aimed to evaluate the impact of the withdrawal of distalgesic in terms of intentional drug overdose (IDO) presentations to hospital emergency departments (EDs) nationally. METHODS: A total of 42,849 IDO presentations to 37 of the 40 hospitals EDs operating in Ireland in 2003-2008 were recorded according to standardised procedures. Data on sales of paracetamol-containing drugs to retail pharmacies for the period 1998-2008 were obtained from IMS Health. RESULTS: The withdrawal of distalgesic from the Irish market resulted in an immediate reduction in sales to retail pharmacies from 40 million tablets in 2005 to 500,000 tablets in 2006 while there was a 48% increase in sales of other prescription compound analgesics. The rate of IDO presentations to hospital involving distalgesic in 2006- 2008 was 84% lower than in the three years before it was withdrawn (10.0 per 100,000). There was a 44% increase in the rate of IDO presentations involving other prescription compound analgesics but the magnitude of this rate increase was five times smaller than the magnitude of the decrease in distalgesic-related IDO presentations. There was a decreasing trend in the rate of presentations involving any paracetamol-containing drug that began in the years before the distalgesic withdrawal. CONCLUSIONS: The withdrawal of distalgesic has had positive benefits in terms of IDO presentations to hospital in Ireland and provides evidence supporting the restriction of availability of means as a prevention strategy for suicidal behaviour.

Factors associated with hospitalization after suicide spectrum behaviors: results from a multicentre study in Spain

Objectives: to identify factors associated with admission after suicide spectrum behaviors. Methods: Patient's characteristics, the nature of their suicidal behavior, admission rates between centres, and factors associated with admission have been examined in suicide spectrum presentations to emergency departments in three Spanish cities. Results: Intent of the suicidal behavior had the greatest impact on hospitalization. Older age, living alone, self-harm method not involving drug overdose, previous history of suicide spectrum behaviors and psychiatric diagnosis of schizophrenia, mood or personality disorder were independently associated with being admitted. There was a three-fold between-centre difference in the rate of hospitalization. Conclusions: widespread differences in the rate of hospitalization were primarily accounted for by characteristics of the individual patients and their suicidal behavior.

Suicide and deliberate self harm in older Irish adults

Background: Hospital-treated deliberate self harm and suicide among older adults have rarely been examined at a national level. Methods: The Irish Central Statistics Office provided suicide and undetermined death data for 1980-2006. The National Registry of Deliberate Self Harm collected data relating to deliberate self harm presentations made in 2006-2008 to all 40 Irish hospital emergency departments. Results: Rates of female suicide among older adults (over 55 years) were relatively stable in Ireland during 1980-2006 whereas male rates increased in the 1980s and decreased in more recent decades. Respectively, the annual male and female suicide and undetermined death rate was 22.1 and 7.6 per 100,000 in 1997-2006. Male and female deliberate self harm was 3.0 and 11.0 times higher at 67.4 and 83.4 per 100,000, respectively. Deliberate self harm and suicide decreased in incidence with increasing age. Deliberate self harm generally involved drug overdose (male: 72%; female 85%) or self-cutting (male: 15%; female 9%). The most common methods of suicide were hanging (41%) and drowning (29%) for men and drowning (39%) and drug overdose (24%) for women. City and urban district populations had the highest rates of hospital-treated self harm. The highest suicide rates were in urban districts. Conclusions: Older Irish adults have high rates of hospital-treated deliberate self harm but below average rates of suicide. Drowning was relatively common as a method of suicide. Restricting availability of specific medications may reduce both forms of suicidal behavior.

Suicide among young people and adults in Ireland: method characteristics, toxicological analysis and substance abuse histories compared

Objective: Information on factors associated with suicide among young individuals in Ireland is limited. The aim of this study was to identify socio-demographic characteristics and circumstances of death associated with age among individuals who died by suicide. Methods: The study examined 121 consecutive suicides (2007–2012) occurring in the southern eastern part of Ireland (Cork city and county). Data were obtained from coroners, family informants, and health care professionals. A comparison was made between 15-24-year-old and 25-34-year-old individuals. Socio-demographic characteristics of the deceased, methods of suicide, history of alcohol and drug abuse, and findings from toxicological analysis of blood and urine samples taken at post mortem were included. Pearson’s χ2 tests and binary logistic regression analysis were performed. Results: Alcohol and/or drugs were detected through toxicological analysis for the majority of the total sample (79.5%), which did not differentiate between 15-24-year-old and 25-34-year-old individuals (74.1% and 86.2% respectively). Compared to 25-34-year-old individuals, 15-24-year-old individuals were more likely to engage in suicide by hanging (88.5%). Younger individuals were less likely to die by intentional drug overdose and carbon monoxide poisoning compared to older individuals. Younger individuals who died between Saturday and Monday were more likely to have had alcohol before dying. Substance abuse histories were similar in the two age groups. Conclusion: Based on this research it is recommended that strategies to reduce substance abuse be applied among 25-34-year-old individuals at risk of suicide. The wide use of hanging in young people should be taken into consideration for future means restriction strategies.

Risk of repeated self-harm and associated factors in children, adolescents and young adults

Background: Repeated self-harm represents the single strongest risk factor for suicide. To date no study with full national coverage has examined the pattern of hospital repeated presentations due to self-harm among young people. Methods: Data on consecutive self-harm presentations were obtained from the National Self-Harm Registry Ireland. Socio-demographic and behavioural characteristics of individuals aged 10–29 years who presented with self-harm to emergency departments in Ireland (2007–2014) were analysed. Risk of long-term repetition was assessed using survival analysis and time differences between the order of presentations using generalised estimating equation analysis. Results: The total sample comprised 28,700 individuals involving 42,642 presentations. Intentional drug overdose was the most prevalent method (57.9%). Repetition of self-harm occurred in 19.2% of individuals during the first year following a first presentation, of whom the majority (62.7%) engaged in one repeated act. Overall, the risk of repeated self-harm was similar between males and females. However, in the 20–24-year-old age group males were at higher risk than females. Those who used self-cutting were at higher risk for repetition than those who used intentional drug overdose, particularly among females. Age was associated with repetition only among females, in particular adolescents (15–19 years old) were at higher risk than young emerging adults (20–24 years old). Repeated self-harm risk increased significantly with the number of previous self-harm episodes. Time differences between first self-harm presentations were detected. Time between second and third presentation increased compared to time between first and second presentation among low frequency repeaters (patients with 3 presentations only within 1 year following a first presentation). The same time period decreased among high frequency repeaters (patients with at least 4 to more than 30 presentations). Conclusion: Young people with the highest risk for repeated self-harm were 15–19-year-old females and 20–24-year-old males. Self-cutting was the method associated with the highest risk of self-harm repetition. Time between first self-harm presentations represents an indicator of subsequent repetition. To prevent risk of repeated self-harm in young people, all individuals presenting at emergency departments due to self-harm should be provided with a risk assessment including psychosocial characteristics, history of self-harm and time between first presentations.

P-glycoprotein inhibition as a strategy to increase drug delivery across the blood-brain barrier: focus on antidepressants

Depression is among the leading causes of disability worldwide. Currently available antidepressant drugs have unsatisfactory efficacy, with up to 60% of depressed patients failing to respond adequately to treatment. Emerging evidence has highlighted a potential role for the efflux transporter P-glycoprotein (P-gp), expressed at the blood-brain barrier (BBB), in the aetiology of treatment-resistant depression. In this thesis, the potential of P-gp inhibition as a strategy to enhance the brain distribution and pharmacodynamic effects of antidepressant drugs was investigated. Pharmacokinetic studies demonstrated that administration of the P-gp inhibitors verapamil or cyclosporin A (CsA) enhanced the BBB transport of the antidepressants imipramine and escitalopram in vivo. Furthermore, both imipramine and escitalopram were identified as transported substrates of human P-gp in vitro. Contrastingly, human P-gp exerted no effect on the transport of four other antidepressants (amitriptyline, duloxetine, fluoxetine and mirtazapine) in vitro. Pharmacodynamic studies revealed that pre-treatment with verapamil augmented the behavioural effects of escitalopram in the tail suspension test (TST) of antidepressant-like activity in mice. Moreover, pre-treatment with CsA exacerbated the behavioural manifestation of an escitalopram-induced mouse model of serotonin syndrome, a serious adverse reaction associated with serotonergic drugs. This finding highlights the potential for unwanted side-effects which may occur due to increasing brain levels of antidepressants by P-gp inhibition, although further studies are needed to fully elucidate the mechanism(s) at play. Taken together, the research outlined in this thesis indicates that P-gp may restrict brain concentrations of escitalopram and imipramine in patients. Moreover, we show that increasing the brain distribution of an antidepressant by P-gp inhibition can result in an augmentation of antidepressant-like activity in vivo. These findings raise the possibility that P-gp inhibition may represent a potentially beneficial strategy to augment antidepressant treatment in clinical practice. Further studies are now warranted to evaluate the safety and efficacy of this approach.

Strategies to prevent potentially inappropriate prescribing and adverse drug reactions in older patients

INTRODUCTION: Potentially inappropriate prescribing (PIP) is a major contributor to adverse drug reactions and overall increased healthcare costs. The aim of this thesis was to identify, develop and implement strategies with the potential to prevent PIP and ADRs in older patients. METHODS: A systematic review of the qualitative literature (Meta-synthesis); A qualitative study in Irish hospitals; A randomised controlled trial (RCT) to assess the impact of an online educational module on doctors’ prescribing knowledge and confidence; Exploration of the potential for a frailty index score to enable doctors identify patients at increased risk of PIP and ADRs; Exploration of the potential for the SHiM tool to enable doctors to optimise prescribing for older patients. RESULTS: The meta-synthesis identified four key concepts: (i) Desire to please the patient; (ii) Feeling of being forced to prescribe; (iii) Tension between experience and guidelines; (iv) Prescriber fear. Similar themes also emerged from the qualitative study. In the RCT, the online educational module resulted in a highly significant 22% difference in test scores between intervention and control groups. The studies exploring the frailty index score showed a significant positive relationship between a patient’s frailty status and their likelihood of experiencing PIP/ADRs. Patients above a frailty threshold of 0.16 were at least twice as likely to experience PIP/ADRs. SHiM was found to be a useful tool in terms of reconciling patients’ medications. However, the evidence for it being capable of preventing clinically relevant adverse events was poor. CONCLUSION:Qualitative research in this thesis has proposed novel theories relating to the causative factors of PIP in older patients. In doing so, it has identified several areas for intervention and laid down a road map for future research.