Examining Quality, Use and Impact of Psychotropic (Use) in older adults with intellectual disabilities (EQUIP): study protocol

Introduction

The greater use of psychotropic medicines in adults with intellectual disability, sometimes in the absence of an emotional/nervous or psychiatric condition, remains controversial and increases risk of medication-related harm^1–6. Older adults with intellectual disability who have mental health conditions represent one of the most vulnerable groups in society⁷. While appropriate use of psychotropic medicines to treat mental illness is critical, overuse of antipsychotics in particular for behaviours that challenge in the absence of a mental health diagnosis has been an international concern. There are also related physical health and mortality concerns that optimal medicines management may avoid. Health needs for people with intellectual disability are already often unmet and unrecognized, and poorer health status may be avoidable^8–11. In particular, the use of psychotropic medications have anticholinergic effects which may cause cognitive impairment, constipation and sedation. Mortality for people with intellectual disability in Ireland is four times higher than for the general population¹².

There has been evidence in Ireland and internationally of inappropriate psychotropic prescribing practices in some institutional settings for people with intellectual disability¹³. Almost 60% of people with intellectual disability reported use of psychotropics and 40% psychotropic polypharmacy within the first wave of the Intellectual Disability Supplement to Irish Longitudinal study on Ageing (IDS-TILDA), ten years ago². The level of intraclass polypharmacy (2+ medicines from the same class) was greatest for antipsychotics (25.6%, 82/319 antipsychotics users) and anxiolytics/hypnotics (26.7%; 59/221 anxiolytics/hypnotics users)². Excessive polypharmacy (10+ psychotropic medicines) was reported by 158/736, 21.5% of people with intellectual disability, compared to 2% in the older adult general population in the TILDA study¹⁴. Some of this prescribing may be historical and reflects that medication are often utilised for decades. In the UK, the Winterbourne View report highlighted serious and systemic findings relating to psychotropic use in residential institutions. As a result, “Stopping overmedication of people with a learning disability, autism or both” (STOMP) was developed by the National Health Service (NHS) England; a multidisciplinary collaboration of patients, carers and healthcare professionals¹⁵. There has been no similar initiative to date in Ireland.

In the past decade deinstitutionalisation in Ireland has been ongoing. The “Time to Move on from Congregated Settings Report” established in 2011 stated that approximately 4,000 people lived in congregated settings (ten or more people living together)¹⁵. The vision of the report set out that “all individuals currently residing in congregated settings will have the opportunity or right to move to a home of their choice in the community”¹⁵. Some evidence suggests that changes in medicines occur following a change of setting. Findings in relation to the influence of place and change of setting on medication use remain inconclusive, with some research suggesting that medication use may increase after community placement^16,17. The specific impact on medicines use in Ireland has yet to be investigated.

The ability to use descriptive and longitudinal methods with existing medicines data in IDS-TILDA to examine the quality, impact and trends of psychotropic prescribing over a decade, will generate evidence to support optimising prescribing development of national guidelines for medicines use. Linkage to the Health Service Executive – Primary Care Reimbursement Service (HSE-PCRS) dispensing data will enrich the analyses by providing additional information on length of exposure to medicines and trends of use, dispensed combinations and adherence issues.

The aim of this study is to examine the quality and trends of psychotropic use of older adults with intellectual disability over a ten-year period in Ireland to inform practice and policy and optimise medicines use and health outcomes. The specific objectives of this study are:

Methods

This retrospective cohort study uses medicines, health and demographic data from four waves of the IDS-TILDA study and data provided from the National Pharmacy Claims database, the HSE-PCRS. The IDS-TILDA was established as a supplement to The Irish Longitudinal Study on Ageing (TILDA)¹⁸. The study is the first of its kind in Europe and is the only study able to directly compare the ageing of people with intellectual disabilities with the general ageing population¹⁸.

Work packages

Five work packages (four discrete and one overlapping work package) will ensure that the aim and objectives stated above are achieved. The main project outcomes are presented within the four discrete work packages (see Table 1), while the explanation of the project outcomes is available in Table 2.

Work package 1 – Examine the effects of psychotropic medicines on cognitive and physical function in older adults with intellectual disability

Study design – The sample population for this work package will be participants who participated in all four waves of IDS-TILDA (n=604). At Wave 2, all IDS-TILDA (n=708) participants were invited to partake in health assessments carried out by a registered nurse in intellectual disability. In total 85% of them (n=602) took part. This included: Quantitative Heel Ultrasound, blood pressure, weight, waist-to-hip ratio, grip strength, timed-up and go. Similar assessments were repeated in Wave 4. In total, at Wave 4, 274 participants were invited to participate in a health assessment fair, of which 260 participated. This lower number was due to the impact of coronavirus disease 2019 (COVID-19) as the health fair had to be ceased. These objective measures included the same measurements as with Wave 2 with additional measurements including balance assessment, activity monitoring, sit to stand assessment, calf measurement, Kardia ECG, and blood samples.

Indicators – Demographics including age, level of intellectual disability, cause of Intellectual disability (Down syndrome/other cause), mobility, living arrangements, sensory and sight difficulties and change in residence between waves will be considered. Cumulative burden of health conditions will be measured using the Functional Comorbidity Index (FCI), addressing confounding by drug indication. Functional status will be assessed by the Barthel Index (BI) Activities of Daily Living. This measures the level of dependence of an individual in ten instrumental activities of daily living (e.g., mobility, using stairs, dressing). It consists of an ordinal scale with range 0–20. A modified form of BI was created for this population²². Behavioural factors, e.g., report of behaviours that challenge will be assessed by specific questions. Mobility will be adjusted for within a regression model relating to falls. The use of objective health measures, such as grip strength, blood pressure, time-up and go, will be considered for inclusion for the sub-population who take part in Waves 2 and 4. Overview of the project outcomes is presented in Table 1 and Table 2.

Analysis - Statistical analysis will be carried out using Excel, SPSS Software Version 27 and STATA. Prevalence of psychotropic use at each wave will be explored and trends will be described. Baseline characteristics of the study population, and longitudinal distribution of the outcome measures at four study timepoints will be described using medians, interquartile ranges (IQR), frequencies, and proportions, as appropriate. This descriptive analysis will inform the approach to the subsequent inferential modelling.

Several multivariate modelling options will be considered to determine the associations between psychotropic exposure and the risk of experiencing each of the outcomes. Outcomes include health status variables measured at Wave 2 and Wave 4 as well as cognitive and physical parameters. These include weighted generalised estimating models, multivariable cox proportional hazard models and Poisson regression. Separate models predicting each of the outcomes will be developed. Models will be adjusted for confounders: baseline age, gender, mobility, number of non-psychotropic medicines reported, baseline cognitive function (TSI), comorbidities (FCI), sociodemographic characteristics. Interactions between psychotropics and confounding variables will be evaluated by testing the statistical significance (p<0.05) of the interaction terms. A variety of adjusted models will be developed to assess the effects of the confounding factors in a group sequential manner. The results will be presented as adjusted odds ratios (OR) and hazard ratios (HR), as appropriate to the model. Kaipen-Meier survival curves will be used to visualise “survival times” (i.e., the time to event, for example, psychotropic exposure and diagnosis of dementia).

The impact of attrition from the waves of the study will be examined due to death, loss to follow up and declined participation. Estimates obtained from the full sample will be compared to a subset of participants who participated in all four time points in the study.

Work package 2 - Assess the change in patterns of psychotropic medicines use among older adults with intellectual disability over a decade

Study design – This work package will use data from the IDS-TILDA study from Wave 1 (2009/2010) and Waves 4 (2019/2020). Additionally, in total, 336 participants (45%) provided consent for linkage of their medicines data for two time points [Wave 3 (2016/2017) and Wave 4 (2019/2020)] and a medical card number. The IDS-TILDA study and HSE-PCRS dataset will be linked by matching the eight-digit unique medical card number provided by the participant. Once linkage is complete, all unique identifiers will be removed. Medication data will be extracted from the HSE-PCRS pharmacy claims database by the PCRS on the basis on GMS identifier for each participant in the present study for the specified months of Waves 3 and 4.

Change in prevalence and pattern of psychotropic medicines and psychotropic polypharmacy (use of two or more psychotropic agents), and their relationship to mental health diagnosis and behaviour that challenge behaviour that challenge at two time points (Wave 1 and Wave 4) will be examined. In addition, there will be linkage to HSE-PCRS dispensing data for a subset of Wave 4 participants who consented to linkage and for whom linkage is successful (Table 1). Analysis of Wave 4 data will be repeated on this subset and compared. The prevalence of any psychotropic medicine at each time point, the number of psychotropic medicines, as well as specific psychotropic medication classes at each time point will be the primary outcomes. Psychotropics will be categorised, as follows: (i) antipsychotic agents, (ii) antidepressants, (iii) anxiolytics/sedative/hypnotics, (iv) mood-stabilising agents (which includes antiepileptics for indications other than epilepsy and lithium)¹⁵. Subcategories of each psychotropic class will be assessed: e.g., atypical/typical antipsychotic. The category ‘taking any psychotropic medication” will be used. Intraclass polypharmacy will be use of two or more agents from within the same therapeutic class². Interclass polypharmacy will be use of two or more psychotropic medications from different therapeutic classes. Total daily doses (TDD) and median daily doses (MDD) will be calculated for both cohorts with available dose information.

Indicators – This work package will investigate: (i) mental health diagnosis, (ii) behaviour that challenge and (iii) healthcare utilisation. Diagnose of epilepsy will be observed as part of antiepileptic drugs use analysis. At each wave, participants were asked “Have you ever received a doctor’s diagnosis of an emotional/nervous or psychiatric condition?” and if yes, “what type of emotional, nervous or psychiatric problems do/does you/she/he have?”. A binary variable will be used (any mental health condition) at both time points (Wave 3 and Wave 4) and mental health conditions categorised². The Behaviour Problem Inventory – Short Form (BPI-S), a validated informant-based questionnaire, was used to record behaviours that challenge at Wave 3 and Wave 4^23,24. Participant’s self-reported psychiatric healthcare utilisation will be examined. This includes if the participant is receiving psychiatric treatment or support such as counselling or behaviour support, and if applicable, who the provider of psychiatric treatment or support is (psychiatrists, GP, other). The covariates for this work package will be sex, age (44–49 years; 50–64 years; 65+ years), level of intellectual disability (mild; moderate; severe/profound), having Down Syndrome or intellectual disability of another aetiology, type of residence (independent, community group home, residential care), change in place of residence. Overview of the project variables is presented in the Table 1.

Analysis – Subject characteristics and reported medicines data will be summarised descriptively with median and IQR for descriptive outcomes and numbers and as percentages for categorical outcomes. The prevalence of any psychotropic medicine at both time points as well as specific psychotropic medication classes will be calculated separately. The prevalence of use by therapeutic class and subclass will be examined and presented for Wave 1 and Wave 4. The median dose of psychotropic medicines for those with dose information at both time points will be compared, and corresponding prevalence of mental health conditions and behaviours that challenge to provide an overall profile of the cohort at both waves, and changes between waves. Analyses will be repeated for participants with linked pharmacy records for Wave 4, with psychotropic use defined according to the medications dispensed in the interview time. The kappa statistics will be used to measure the agreement between the two sources (self-report data and HSE-PCRS data) at Wave 4²⁵. Patient characteristics will be compared for those with and without data linkage²⁵.

Comparison between psychotropic use, mental health conditions, behaviour that challenge, and healthcare utilisation, change of residence, between the two waves will be performed. A Wald test of two prevalence estimates will be carried out. Because use of psychotropic medicines is also associated with age and presence of mental health conditions, changes in the subpopulation age may affect overall prevalence of use. Two-way repeated measures analyses of variance will be used to examine changes in the proportion of individuals taking psychotropic medications and in the number of medications taken over time. Several multivariate modelling approaches will be considered, including logistic regression of imbalanced classes, log linear modelling and decision trees.

The impact of attrition from the waves of the study will be examined due to death, loss to follow up and declined participation. Estimates obtained from the full sample will be compared to a subset of participants who participated in all four time points in the study.

Work package 3 – Assess the influence of change in place of residence on psychotropic use patterns in older adults with intellectual disability over a decade

Study design – At each wave of the IDS-TILDA study, participants are categorised as living independently/with family, in a community group home or institution (>10 people). Movers will be identified as those who changed place of residence between each wave and reported this change on both the PIQ and CAPI. In relation to psychotropic medicines, it will be assessed if participants have commenced new psychotropic medicines or increased/decreased dosage of existing medicines between waves.

Indicators – The covariates in this work package will be sex, level and type of intellectual disability. The confounders are a new mental health diagnosis between each wave, behaviour that challenge, and a new diagnosis of epilepsy and/or dementia.

Analysis – The median (IQR) number of psychotropic medicines will be calculated for participants at waves 1–4 and the change of median psychotropic medicines over time will be assessed. The median doses of psychotropic medicines for those with dose information at each time point will be calculated, and any corresponding prevalence of mental health conditions and behaviours that challenge will be identified to provide an overall profile of the cohort at each wave, and changes between the waves. For each psychotropic medication class there will be four categories between each wave: none (no use at both waves), new (no use at baseline wave and new use at next Wave), discontinued (use at baseline wave and no use at next wave), and recurrent (use at both waves). For those with available dosing data at time points we will also examine change in dose between each time point. A transition matrix will be created to indicate the percentage of cases in each initial category that remain in the category or switch category at each wave. Change in place of residence over time will be assessed in a similar way between each wave i.e., between wave 1 to 2, from wave 2–3 and wave 3–4. There will be four categories: no change in place of residence, community-based move, lateral move, higher support setting move. These will be assigned a score and a change variable will be created with levels and calculated at each wave.

Several models to represent the influence of change in residence on change of psychotropic use will be considered including Multilevel General Estimating Equation modelling and the conditional change model (lagged endogenous variable model). Models will be adjusted for confounders. Models will be estimated accounting for clustering of repeated exposure periods within participants. Analyses will be stratified by age to test whether associations between medicines and outcomes varied by age. For each medication class, four categories of exposure will be considered: none (no use at either wave), new (no use at baseline wave and use at follow-up wave), discontinued (use at baseline wave and no use at follow-up wave), and recurrent (use at both waves).

Work package 4 – Investigate changes in the prevalence and patterns of psychotropic use in two cohorts of adults aged 40–49 years with intellectual disability separated by a 10-year period and associated mental health diagnosis and behaviours that challenge

Study design - The samples for this study will be drawn from Waves 1 (2009/2010), and Wave 4 (2019/2020) of the IDS-TILDA study. There were 135 new participants recruited at Wave 4 aged 40–49 years and they will represent the sample for 40–49-year-old cohort at Wave 4 in this study. At Wave 1 in 2009/2010 there were 274 adults aged 40–49 years and these will represent the cohort for Wave 1 of the study.

Indicators – Demographic and clinical characteristics in this work package will be sex, level and type of intellectual disability, type of residence, reported mental health conditions and behaviours that challenge. Health care utilisation in the previous 12 months will be examined (GP visits, outpatient visits, Accident and Emergency visits, hospital admission). Participant’s self-reported psychiatric and psychological healthcare utilisation will be examined at both time points. The availability of easy-read medicines information will also be analysed. The confounders are the reported diagnosis or epilepsy and/or dementia.

Analysis – Descriptive analyses will examine prevalence and patterns of psychotropic use, including subcategories for the two cohorts separately and associations with demographic and clinical characteristics. The prevalence of psychotropic medicines classes will be estimated. Unpaired t-tests and Mann-Whitney and ANOVA tests will be used to compare the two cohorts. Binary logistic regression will be performed to estimate odds ratios for “any psychotropic” in Wave 4 participants compared to those at Wave 1, adjusting for confounders. Patterns of psychiatric healthcare utilisation and availability of easy-to-read medicines information will be compared for those at Wave 1 and those at Wave 4.

Work package 5 – Ensure patients and key stakeholders are involved in a meaningful and informative manner from inception to dissemination

IDS-TILDA have well established consultation processes with advocacy groups in several service providers throughout the country. These groups will be invited to contribute to the review of the project goals and establish the knowledge base, in collaboration with the HSE task group. An independent advocate will be included on the project management group. Robust dissemination will be undertaken to ensure all stakeholder needs are met, including the production of an easy read accessible findings report. Dissemination will be conducted via infographics, videos and educational webinars as well as a webpage on the TCAID website which will act as an information hub for the project. Working with the consultation advocacy groups and the HSE task group, the main findings will be produced into easy read formats. The advocacy and focus groups will review the report for clarity, understanding and accessibility. The project will engage in national and international dissemination through peer review publications, position papers, conferences, and invited talks with service providers and advocacy groups. The consultation advocacy groups will also contribute to the identification of priorities for practice emanating from the findings of the project and translation into a meaningful tool to inform, educate and empower the end-user in practice, e.g., development of psychotropic prescribing guidelines that are patient-centred.

Discussion

The aim of this study is to examine the quality and trends of psychotropic use of older adults with intellectual disability over a ten-year period in Ireland to inform practice and policy and optimise medicines use and health outcomes. This study will add value for the population of older adults with intellectual disability by revealing the following: (i) the effects of psychotropic medicines on cognitive and physical functions, (ii) the change in patterns in psychotropic medicines, (iii) the influence of different factors (e.g., change in place of residence) on psychotropic use patterns, and (iv) the differences in psychotropic prescribing patterns for those age 40–49 years in 2009/2010 and those aged 40–49 years who were newly recruited in Wave 4 in 2019/2020. Finally, the findings will be used by the HSE to influence policy and improve prescribing. The objectives noted above will be achieved through the completion of 4 work packages, outlined in the Methods section.

Work package 1 will add to existing research on the effects of psychotropic medicines. Previous research has investigated medication use in adults with intellectual disability^1,2,26 however there remains a large knowledge gap in this area which work package 1 will address, specifically in relation to cognitive and physical function.

This work package will also address whether deinstitutionalisation of adults with intellectual disability will have resulted in changes in medications.

Work package 2 will utilise data from both 10-year IDS-TILDA and HSE-PCRS to assess potential changes in medication usage, with particular interest in patterns of psychotropic medicines. Work package 3 compliments work package 2 by examining the influence of change in residence and its impact on psychotropic use. No similar comparative study has been conducted before in Ireland.

Work package 4 will allow for assessment on the trends of medication prescribing in the youngest cohort in Wave 1 and Wave 4 (40–49 years). Similar work has not been conducted before in Ireland.

The findings from the four work packages will then inform the formation of prescribing guidelines on psychotropic medicine use in adults with intellectual disability as well as audit-standards for anti-psychotic medications in this cohort. Results will be comparable with international findings and provide some key opportunities and recommendations for future research. Study findings will be disseminated via publications in peer reviewed journals and presented at relevant conferences. Adults with intellectual disability and other stakeholders will be involved from the beginning of the study up to its conclusion and will be involved in drafting articles, presentations, triangulation of evidence and development of easy read materials in order to empower individuals with intellectual disability with knowledge on medicines, medicine use and medicine management.

Reporting guidelines

This study will follow the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) standardised reporting guidelines for cohort studies⁶.

Study status

Work package 1 is almost completed and components of work packages 2, 3 and 4 have been completed. A steering group has been formed which correlates with work package 5.