Antihistamine-related deaths in England: Are the high safety profiles of antihistamines leading to their unsafe use?

AIMS: Antihistamines are routinely taken to control allergic reactions or sedation to induce sleep. There are, however, growing concerns regarding sedating antihistamine misuse. This research aims to evaluate deaths related to antihistamines in England occurring during 2000-2019. METHODS: Cases reported to the National Programme on Substance Abuse Deaths from England occurring in 2000-2019 with antihistamine detections at postmortem were extracted for analysis. RESULTS: In total, 1666 antihistamine postmortem detections were identified from 1537 cases. Sedating antihistamines available for purchase under pharmacist supervision but without need for a prescription (pharmacy-only medications) were present in a significant majority of cases (85.2%, P < .01). Despite an increasing trend for antihistamine-related deaths over time, the proportion of deaths where an antihistamine was implicated declined over the same period. Specific concerns with regards to the misuse of these pharmacy-only sedating antihistamines are raised with regards to the significant proportion of cases that were concluded as suicide (20.9%, P < .01), and the high prevalence of their use in combination with other central nervous system depressants (94.8% of cases). CONCLUSION: This is the first report in over 40 years regarding antihistamine-related mortality from England. The rising trend in sedating antihistamine-related deaths may be contributed to by their increasing availability and the perceived negligible dangers associated with antihistamines, both from the general public and learned professionals. Awareness of the dangerous sedative properties that some antihistamines possess is, however, heightened in individuals deliberately seeking these effects. Urgent review of sedating antihistamines currently assigned under the pharmacy-only classification is needed to achieve antihistamine harm reduction.

Involvement of propranolol in suicides: cross-sectional study using coroner-reported data.

BACKGROUND: Propranolol is a beta-blocker medication indicated mostly for heart rhythm conditions and for physical symptoms of anxiety. Prescriptions for propranolol in the UK have increased since 2008. Recently, there have been concerns about the involvement of propranolol in intentional poisonings, but such deaths are not routinely reported. Therefore, use of coroner-reported and toxicology data enables unique investigation into the scale of involvement of propranolol in suicide. AIMS: To describe the extent to which propranolol is involved in suicides, including patterns over time and characteristics of people whose suicide involved propranolol compared with other suicides. METHOD: Data were derived from the National Programme on Substance Use Mortality (NPSUM). All suicides and deaths of undetermined intent between 2010 and 2021 in England, Wales and Northern Ireland were extracted, and a subset was identified where propranolol was involved in death. RESULTS: There were 4473 suicides of which 297 (6.6%) involved propranolol, with the proportion involving propranolol nearly quadrupling during the study period (3.4% v. 12.3%). Compared with all other suicides, a greater proportion of propranolol suicides were in women (56.6% v. 37.1%) and in people with diagnoses of depression (39.1% v. 27.1%) and anxiety (22.2% v. 8.6%). When suicide involved propranolol, an antidepressant was detected at post-mortem in 81.8% of deaths, most commonly a selective serotonin reuptake inhibitor (SSRIs) (51.5%), and most often citalopram (24.6%). CONCLUSIONS: A small number, but increasing proportion, of suicides reported to the NPSUM involve propranolol. Vigilance to the combined toxicity profile of medicines used alongside propranolol may be pertinent.

Experience and attitudes of pharmacy teams towards suicide prevention: A cross-sectional survey.

BACKGROUND: Community pharmacists are increasingly recognized as integral members in suicide prevention programs, as part of a multidisciplinary and multifaceted approach. However, further research is required to understand then optimize the whole pharmacy teams' role across sectors. OBJECTIVE: To explore pharmacy teams' experience of, and attitudes towards, suicide prevention in England. METHODS: A cross-sectional survey was purposively distributed to pharmacy staff in England before accessing an optional suicide awareness raising video, hosted by Centre for Pharmacy Postgraduate Education (CPPE), in September 2019-March 2021. Questions included demographics and experience of, attitudes towards, and preparedness for, suicide prevention. The 14-item Attitudes to Suicide Prevention (ASP) scale was used (possible range 14-70 with lower scores representing positive attitudes). Descriptive and comparative statistics were reported. Free-text comments were invited to explore respondents' experience of suicide prevention and reflexive thematic analysis used. RESULTS: Of 403 respondents, 82% were female; most were pharmacists (59%) or pharmacy technicians (21%), with the remainder having other roles. Eighty-five percent worked in community pharmacy. Eleven percent had prior suicide prevention training, and 71% reported interacting with at least one patient about suicide. Most often, suicidality was disclosed by the patient (40%), with 6% of pharmacy staff having directly asked a patient about suicidal behavior or plans. The aggregated ASP score was 31.51 (SD 6.23), and role did not affect experience or attitude. Pharmacy teams' experiences of suicide prevention can be summarized by three major themes i) Exposure to suicide; ii) Responsibility for action; and iii) Access to means of suicide. CONCLUSIONS: Pharmacy teams felt responsibility in caring for those at risk of suicide and had experience of this. Further training should include understanding of medicines means restriction and involve all roles and sectors of pharmacy. Pharmacy teams should be integrated into the 'circle of care' to access referral pathways.

Does video e-learning improve pharmacy teams' attitudes and preparedness towards suicide prevention?

Background: Evidence on the role of pharmacy teams in suicide prevention is growing. To support pharmacy teams, a video e-learning was produced by the Centre for Pharmacy Postgraduate Education (CPPE) involving an 'on-the-sofa' style group interview with people with personal and professional experience of suicide and suicide research. Objective: The objective was to measure any change in attitudes and preparedness for suicide prevention, following a video e-learning produced for pharmacy staff. Methods: People working in any sector of pharmacy in England and who accessed the training video were invited to complete a pre- and post- training questionnaire, between September 2019 and March 2021. Question types included demographics, experiences, attitudes as measured by the Attitudes to Suicide Prevention (ASP) scale, and preparedness. Descriptive statistics were used to summarize demographics and experience and paired t-tests were used to compare pre- and post- questionnaire responses. Results: Both questionnaires were completed by 147 people. Most worked in community pharmacy (88%) and were pharmacists (64%) or pharmacy technicians (20%). Attitudes to suicide prevention improved significantly (pre:31.20 (SD 6.04); post:28.40 (SD 6.50), p < 0.0001) after watching the video, as did self-reported preparedness. Conclusions: Pharmacy teams' self-reported attitudes and preparedness for suicide prevention improved after watching this suicide awareness video compared to baseline. Suicide awareness training tailored to pharmacy teams may be valuable, but the longitudinal impact of any suicide prevention training requires further exploration.

Suicide Prevention in Nigeria: Can Community Pharmacists Have a Role?

Suicide is a global public health problem and is among the leading causes of death worldwide. Over 700,000 people die by suicide globally each year, affecting all ages, genders, and regions. Community pharmacists are easily accessible and trusted frontline healthcare professionals. They provide pharmaceutical care to the community, yet their role is still yet to be fully optimised. With the expanding role of community pharmacists and their constant accessibility to the local population, they could have a potential role in suicide prevention and awareness in Nigeria through restriction of means, signposting to services, and conversations with patients built on trusting relationships. In this commentary, we review the literature on the involvement of community pharmacists in suicide prevention. In addition, we discuss the potential role of community pharmacists in Nigeria through establishing trusting relationships with patients, clinical counselling, and medication gatekeeping, given the existing gaps in knowledge and awareness of suicide prevention within community settings. This commentary also outlines potential barriers and solutions, making suggestions for future research.

Advancing Mental heaLth Provision In PHarmacY (AMPLIPHY): A feasibility study.

BACKGROUND: Specifically-designed community pharmacy-based services represent opportunities to support people with their mental health. As few such services exist worldwide, the Advancing Mental HeaLth Provision In PharmacY (AMPLIPHY) was designed with stakeholders. The purpose was to support people with their mental health when initiated on new prescription or change in drug, dose or quantity of antidepressant, through a series of consultations (up to 3 months). OBJECTIVE(S): The aim was to evaluate the feasibility of the AMPLIPHY service. The objectives were to: i) pilot the service; ii) examine anonymous consultation data to understand patients' characteristics, priorities and consultation focus and iii) Evaluate pharmacists' experiences. METHODS: This service evaluation involved a concurrent mixed methods design. Patient characteristics were extracted from consultation notes and descriptive statistics applied. Content analysis was used to summarise consultation foci and comparisons between patients' priorities with consultation content were made. Pharmacists were interviewed at the start (n = 10) and end (n = 4) of the pilot with themes identified using thematic analysis. RESULTS: Seventy-six patients participated (63% of recruitment target). The median age was 39 (IQR 28-47) and 62% were female. Seventy percent of patients had one consultation, 26% had two and 4% had three. Prescription for new antidepressant was the most common reason for entry (74%) and sertraline was most prescribed (46%). Consultations commonly focussed on life experience (n = 51), medication (n = 47), health (n = 42), support (n = 36) and patients' expression of their feelings (n = 31). The pharmacists' experiences were summarised in three themes: i) Motivation, ii) Practicalities and iii) Experience and Outcomes. CONCLUSIONS: Pharmacists were motivated to deliver this novel service and some patients were willing to join the service. Analysis of patient demographics, consultation notes and interviews provide insight into the strengths and challenges of the service and provides a blueprint for future service developments.

Suicide rates amongst individuals from ethnic minority backgrounds: A systematic review and meta-analysis.

Background: Existing evidence suggests that some individuals from ethnic minority backgrounds are at increased risk of suicide compared to their majority ethnic counterparts, whereas others are at decreased risk. We aimed to estimate the absolute and relative risk of suicide in individuals from ethnic minority backgrounds globally. Methods: Databases (Medline, Embase, and PsycInfo) were searched for epidemiological studies between 01/01/2000 and 3/07/2020, which provided data on absolute and relative rates of suicide amongst ethnic minority groups. Studies reporting on clinical or specific populations were excluded. Pairs of reviewers independently screened titles, abstracts, and full texts. We used random effects meta-analysis to estimate overall, sex, location, migrant status, and ancestral origin, stratified pooled estimates for absolute and rate ratios. PROSPERO registration: CRD42020197940. Findings: A total of 128 studies were included with 6,026,103 suicide deaths in individuals from an ethnic minority background across 31 countries. Using data from 42 moderate-high quality studies, we estimated a pooled suicide rate of 12·1 per 100,000 (95% CIs 8·4-17·6) in people from ethnic minority backgrounds with a broad range of estimates (1·2-139·7 per 100,000). There was weak statistical evidence from 51 moderate-high quality studies that individuals from ethnic minority groups were more likely to die by suicide (RR 1·3 95% CIs 0·9-1·7) with again a broad range amongst studies (RR 0·2-18·5). In our sub-group analysis we only found evidence of elevated risk for indigenous populations (RR: 2·8 95% CIs 1·9-4·0; pooled rate: 23·2 per 100,000 95% CIs 14·7-36·6). There was very substantial heterogeneity (I2  > 98%) between studies for all pooled estimates. Interpretation: The homogeneous grouping of individuals from ethnic minority backgrounds is inappropriate. To support suicide prevention in marginalised groups, further exploration of important contextual differences in risk is required. It is possible that some ethnic minority groups (for example those from indigenous backgrounds) have higher rates of suicide than majority populations. Funding: No specific funding was provided to conduct this research. DK is funded by Wellcome Trust and Elizabeth Blackwell Institute Bristol. Matthew Spittal is a recipient of an Australian Research Council Future Fellowship (project number FT180100075) funded by the Australian Government. Rebecca Musgrove is funded by the NIHR Greater Manchester Patient Safety Translational Research Centre (PSTRC-2016-003).

Alcohol-Specific Mortality in People With Epilepsy: Cohort Studies in Two Independent Population-Based Datasets.

Objectives: The risk of dying by alcohol-specific causes in people with epilepsy has seldom been reported from population-based studies. We aimed to estimate the relative risk of alcohol-specific mortality in people with epilepsy, and the extent to which problematic alcohol use was previously identified in the patients' medical records. Method: We delineated cohort studies in two population-based datasets, the Clinical Practice Research Datalink (CPRD GOLD) in England (January 01, 2001-December 31, 2014) and the Secure Anonymised Information Linkage (SAIL) Databank in Wales (January 01, 2001-December 31, 2014), linked to hospitalization and mortality records. People with epilepsy were matched to up to 20 persons without epilepsy on gender, age (±2 years) and registered general practice. We identified alcohol-specific death from Office for National Statistics (ONS) records using specified ICD-10 codes. We further identified prescriptions, interventions and hospitalisations related to alcohol use. Results: In the CPRD GOLD, we identified 9,871 individuals in the incident epilepsy cohort and 185,800 in the comparison cohort and, in the SAIL Databank, these numbers were 5,569 and 110,021, respectively. We identified a five-fold increased risk of alcohol-specific mortality in people with epilepsy vs. those without the condition in our pooled estimate across the two datasets (deprivation-adjusted HR 4.85, 95%CI 3.46-6.79). Conclusions: People with epilepsy are at increased risk of dying by an alcohol-specific cause than those without the disorder. It is plausible that serious alcohol misuse could either contribute to the development of epilepsy or it could commence subsequent to epilepsy being diagnosed. Regardless of the direction of the association, it is important that the risk of dying as a consequence of alcohol misuse is accurately quantified in people affected by epilepsy. Systematically-applied, sensitive assessment of alcohol consumption by healthcare professionals, at opportunistic, clinical contacts, with rapid access to quality treatment services, should be mandatory and play a key role in reduction of health harms and mortality.

Current and potential contributions of community pharmacy teams to self-harm and suicide prevention: A qualitative interview study.

BACKGROUND: Suicide prevention is a global priority. Despite the focus on primary care in suicide prevention, little is known about the contributory role of community pharmacists and nothing about the role of the wider community pharmacy team in this area. We aimed to explore the current and potential role of community pharmacy teams in self-harm and suicide prevention. METHODS: We conducted one-to-one semi-structured qualitative interviews with community pharmacy staff (pharmacists, pre-registration pharmacists, pharmacy technicians, dispensing/pharmacy assistants, delivery drivers) in the North West of England, UK. We identified themes from the interview transcripts through an iterative process of inductive thematic analysis. RESULTS: We conducted twenty-five interviews with community pharmacy staff. Many described examples of helping those who were contemplating suicide or self-harm. No participants had received suicide prevention training. We identified six themes. The first two themes (i) Relationship with Patient and (ii) Pharmacy environment were seen as facilitators, which, if supported by (iii) Training, could underpin the final three themes: (iv) Opportunities for contact, (v) Facilitated referral pathway and (v) Restricting access to means. The distinct lack of training should be overcome with evidence-informed training. Referral pathways should be clear and enable direct and accessible referral by community pharmacy teams. There are opportunities for existing pharmacy services and schemes to be adapted to maximise suicide and self-harm prevention activities. Pharmacy teams did not identify themselves to have a clear role in restricting access to medication. CONCLUSIONS: Pharmacy teams already support patients in relation to self-harm and suicide, often relying on their personal experience in the absence of formal training. With the implementation of evidence-informed training and clear referral pathways, this could be done in a more effectively.

Risk factors for self-harm in people with epilepsy.

OBJECTIVE: To estimate the risk of self-harm in people with epilepsy and identify factors which influence this risk. METHODS: We identified people with incident epilepsy in the Clinical Practice Research Datalink, linked to hospitalization and mortality data, in England (01/01/1998-03/31/2014). In Phase 1, we estimated risk of self-harm among people with epilepsy, versus those without, in a matched cohort study using a stratified Cox proportional hazards model. In Phase 2, we delineated a nested case-control study from the incident epilepsy cohort. People who had self-harmed (cases) were matched with up to 20 controls. From conditional logistic regression models, we estimated relative risk of self-harm associated with mental and physical illness comorbidity, contact with healthcare services and antiepileptic drug (AED) use. RESULTS: Phase 1 included 11,690 people with epilepsy and 215,569 individuals without. We observed an adjusted hazard ratio of 5.31 (95% CI 4.08-6.89) for self-harm in the first year following epilepsy diagnosis and 3.31 (95% CI 2.85-3.84) in subsequent years. In Phase 2, there were 273 cases and 3790 controls. Elevated self-harm risk was associated with mental illness (OR 4.08, 95% CI 3.06-5.42), multiple general practitioner consultations, treatment with two AEDs versus monotherapy (OR 1.84, 95% CI 1.33-2.55) and AED treatment augmentation (OR 2.12, 95% CI 1.38-3.26). CONCLUSION: People with epilepsy have elevated self-harm risk, especially in the first year following diagnosis. Clinicians should adequately monitor these individuals and be especially vigilant to self-harm risk in people with epilepsy and comorbid mental illness, frequent healthcare service contact, those taking multiple AEDs and during treatment augmentation.

Risk of Unnatural Mortality in People With Epilepsy.

Importance: People with epilepsy are at increased risk of mortality, but, to date, the cause-specific risks of all unnatural causes have not been reported. Objective: To estimate cause-specific unnatural mortality risks in people with epilepsy and to identify the medication types involved in poisoning deaths. Design, Setting, and Participants: This population-based cohort study used 2 electronic primary care data sets linked to hospitalization and mortality records, the Clinical Practice Research Datalink (CPRD) in England (from January 1, 1998, to March 31, 2014) and the Secure Anonymised Information Linkage (SAIL) Databank in Wales (from January 1, 2001, to December 31, 2014). Each person with epilepsy was matched on age (within 2 years), sex, and general practice with up to 20 individuals without epilepsy. Unnatural mortality was determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes V01 through Y98 in the Office for National Statistics mortality records. Hazard ratios (HRs) were estimated in each data set using a stratified Cox proportional hazards model, and meta-analyses were conducted using DerSimonian and Laird random-effects models. The analysis was performed from January 5, 2016, to November 16, 2017. Exposures: People with epilepsy were identified using primary care epilepsy diagnoses and associated antiepileptic drug prescriptions. Main Outcomes and Measures: Hazard ratios (HRs) for unnatural mortality and the frequency of each involved medication type estimated as a percentage of all medication poisoning deaths. Results: In total, 44 678 individuals in the CPRD and 14 051 individuals in the SAIL Databank were identified in the prevalent epilepsy cohorts, and 891 429 (CPRD) and 279 365 (SAIL) individuals were identified in the comparison cohorts. In both data sets, 51% of the epilepsy and comparison cohorts were male, and the median age at entry was 40 years (interquartile range, 25-60 years) in the CPRD cohorts and 43 years (interquartile range, 24-64 years) in the SAIL cohorts. People with epilepsy were significantly more likely to die of any unnatural cause (HR, 2.77; 95% CI, 2.43-3.16), unintentional injury or poisoning (HR, 2.97; 95% CI, 2.54-3.48) or suicide (HR, 2.15; 95% CI, 1.51-3.07) than people in the comparison cohort. Particularly large risk increases were observed in the epilepsy cohorts for unintentional medication poisoning (HR, 4.99; 95% CI, 3.22-7.74) and intentional self-poisoning with medication (HR, 3.55; 95% CI, 1.01-12.53). Opioids (56.5% [95% CI, 43.3%-69.0%]) and psychotropic medication (32.3% [95% CI, 20.9%-45.3%)] were more commonly involved than antiepileptic drugs (9.7% [95% CI, 3.6%-19.9%]) in poisoning deaths in people with epilepsy. Conclusions and Relevance: Compared with people without epilepsy, people with epilepsy are at increased risk of unnatural death and thus should be adequately advised about unintentional injury prevention and monitored for suicidal ideation, thoughts, and behaviors. The suitability and toxicity of concomitant medication should be considered when prescribing for comorbid conditions.

Non-psychotropic medication and risk of suicide or attempted suicide: a systematic review.

OBJECTIVES: To establish which non-psychotropic medications have been assessed in relation to risk of suicide or attempted suicide in observational studies, document reported associations and consider study strengths and limitations. DESIGN: Systematic review. METHODS: Four databases (Embase, Medline, PsycINFO and International Pharmaceutical Abstracts) were searched from 1990 to June 2014, and reference lists of included articles were hand-searched. Case-control, cohort and case only studies which reported suicide or attempted suicide in association with any non-psychotropic medication were included. OUTCOME MEASURES: The outcomes eligible for inclusion were suicide and attempted suicide, as defined by the authors of the included study. RESULTS: Of 11,792 retrieved articles, 19 were eligible for inclusion. Five studies considered cardiovascular medication and antiepileptics; two considered leukotriene receptor antagonists, isotretinoin and corticosteroids; one assessed antibiotics and another assessed varenicline. An additional study compared multiple medications prescribed to suicide cases versus controls. There was marked heterogeneity in study design, outcome and exposure classification, and control for confounding factors; particularly comorbid mental and physical illness. No increased risk was associated with cardiovascular medications, but associations with other medications remained inconclusive and meta-analysis was inappropriate due to study heterogeneity. CONCLUSIONS: Whether non-psychotropic medications are associated with increased risk of suicide or attempted suicide remains largely unknown. Robust identification of suicide outcomes and control of comorbidities could improve quantification of risk associated with non-psychotropic medication, beyond that conferred by underlying physical and mental illnesses.