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Research in Social and Administrative Pharmacy
journal homepage: www.elsevier.com/locate/rsap
Primary care healthcare professionals supporting patients to discontinue antidepressants: A scoping review of barriers, enablers and interventions
Bethany Atkins3, Michelle Maden , Linda Birta, Samuel Tromans'’1, Zoe Swithenbanke, Olivia Rose Kersey , Pam Smith , Sion Scotta’
a School of Healthcare, University of Leicester, UK
b Department of Health Data Science, University of Liverpool, UK
c Department of Population Health Sciences, University of Leicester, UK
d Adult Learning Disability Service, Leicestershire Partnership NHS Trust, Leicester, UK
e Lancaster University, Lancaster, UK
r Public and Patient Involvement member, School of Healthcare, University of Leicester, UK

ARTICLE INFO
ABSTRACT

Keywords: Deprescribing Psychotropic Mental health Depression Anxiety Determinants General practice

Background: Antidepressants are prescribed to treat a range of common mental disorders (CMDs) including depression and anxiety. Most people are prescribed antidepressants for longer than is necessary, leading to avoidable long-term side-effects and exacerbated withdrawal effects, if they eventually discontinue taking them. There is a need for interventions to address the barriers and enablers (determinants) of healthcare professionals (HCPs) who support people to discontinue antidepressants when they are no longer needed.
Objective: This scoping review aimed to examine the evidence base regarding the barriers and enablers to HCPs in primary care discontinuing antidepressants prescribed for mild-moderate mental health conditions, as well as interventions to facilitate HCPs to effectively support patients through the discontinuation process.
Methods: Studies were identified by undertaking a keyword search of the databases MEDLINE, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL). All peer-reviewed studies from inception to January 2024 were included. Two reviewers independently screened studies and extracted data. Findings were synthesised narratively.
Results: Two hundred and fifty-three studies were included in title and abstract screening and 30 studies proceeded to full-text screening. Seventeen studies were included; nine reported HCP barriers and/or enablers and eight reported interventions. Time constraints, conflicting priorities and fear of CMD relapse are commonly reported barriers whilst knowledge and skills about how to discontinue antidepressants were the main enablers. Interventions primarily involved education and training for HCPs and provision of information about how to taper antidepressants.
Discussion: Whilst existing interventions address the main enablers to HCPs discontinuing antidepressants, inclusion of components to address the barriers is a notable omission and may explain the lack of efficacy of existing interventions. Future interventions should be developed using appropriate theory and address all determinants of HCPs supporting people to discontinue antidepressants.

1. Background
One in eight people globally live with a mental health condition, with the most frequent being a common mental disorder (CMD) such as depression or anxiety.1,2 Higher rates are reported in Western countries; the 2014 Adult Psychiatric Morbidity Survey reported that one in six adults in England have a CMD and the 2021 National Survey on Drug

Use and Health estimates that one in five Americans experience a mental illness each year.3,4 Guidelines recommend non-pharmacological treatment such as cognitive behavioural therapy as first line treatment for mild and moderate CMDs,5 however inequity in provision of non-pharmacological treatment often results in antidepressants being prescribed instead. Antidepressant medicines are the mainstay of pharmacological treatment for CMDs and prescribing has increased year

* Corresponding author.
E-mail address: s.scott@leicester.ac.uk (S. Scott).
https://doi.Org/10.1016/j.sapharm.2025.02.004
Received 26 September 2024; Received in revised form 28 January 2025; Accepted 5 February 2025
Available online 8 February 2025
1551-7411/© 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.0rg/licenses/by/4.0/).
on year since the 1980s. Approximately 10 % of adults in England take an antidepressant for depression or anxiety.‘
A broad group of medicines exist to manage CMDs. These include selective serotonin reuptake inhibitors (SSRIs), e.g., sertraline, serotonin norepinephrine reuptake inhibitors (SNRIs), e.g., duloxetine, noradrenaline and specific serotonergic antidepressants (NASSAs) e.g., mirtazapine, and finally tricyclic antidepressants, e.g., amitriptyline. Antidepressants provide symptom relief to help people during an acute life event or whilst the underlying cause is addressed, for example through psychotherapies. Like all medicines, antidepressants can cause side effects. A cohort study in the Netherlands reported that 64 % of people who had been taking an antidepressant for 12 months on average experienced approximately three side effects. Whilst some side effects such as nausea are relatively mild and short lasting, others are potentially serious and people are more likely to experience them the longer they have been taking their antidepressant. Side effects such as sleep disturbance, excess sweating and sexual dysfunction can be serious, permanent and debilitating, lead to a significant adverse impact on people’s quality of life and therefore it is imperative that antidepressants are only prescribed for as long as is necessary.
Antidepressants are associated with withdrawal reactions including flu-like symptoms, sensory disturbances and agitation. These reactions can occur during managed tapering and sudden discontinuation, and may be mild and last a few weeks or severe, lasting months or in some cases years. A systematic review of the incidence and severity of antidepressant withdrawal reactions reported a weighted average incidence rate of 56 %, with 46 % of people who experience withdrawal reactions describing them as extreme in severity. Increased duration of antidepressant use is associated with both increased incidence and severity of withdrawal effects, and there is weak evidence that higher doses are also associated with these outcomes. It is therefore essential that people only take antidepressants for as long as is necessary. Most people do not need to take antidepressants for more than 6-12 months and prescribing guidelines only recommend continuation beyond this in instances where there is a high risk of relapse. Even in these situations, patients should be fully informed of the risks of continuing antidepressants long term. ‘ However, most people end up taking an antidepressant beyond resolution of the original prescribing indication, 4 for at least two years, with cohort studies in the UK and USA reporting that people take antidepressants for approximately five years on average. ■ Accordingly, there is a need for strategies to change practice to ensure people do not take antidepressants for longer than is necessary.
Most antidepressants are prescribed by primary care healthcare professionals (HCPs), therefore they are responsible for supporting people to discontinue them when they are no longer indicated. Guidelines providing information regarding the recommended duration of antidepressant prescribing and tapering strategies to reduce the risk of withdrawal effects are available and address knowledge and skills barriers. ’ However, there is a plethora of research from the field of behavioural science and deprescribing suggesting interventions providing information alone are unlikely to result in a change in practice. ’ There is a need to establish what is already known about the barriers and enablers to primary care HCPs discontinuing antidepressants to direct future research. There is also a need to identify existing interventions to facilitate primary care HCPs to discontinue antidepressants and report the barriers and enablers to deprescribing that they are designed to address.
This scoping review aimed to examine the evidence base regarding the barriers and enablers to HCPs in primary care discontinuing antidepressants prescribed for CMDs, as well as interventions to facilitate them in effectively supporting people through the discontinuation process. The objectives were to describe the scale, range, and key characteristics of the evidence regarding the barriers and enablers to HCPs in primary care discontinuing antidepressants and interventions intended to facilitate HCPs to support patients through the discontinuation process.
2.		Methods
This scoping review was developed in accordance with the five-stage methodological framework outlined by Arksey and O'Malley2: Identifying the research question(s), identifying relevant studies, study selection, charting the data and collating, summarising and reporting the results. The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) was used to guide reporting of the study results - see Appendix 1. The review protocol for this study is publicly available.
A Research Advisory Group (RAG) comprising six people prescribed an antidepressant and having experienced and not experienced side effects and withdrawal effects provided the lived experience perspective throughout the review process. The RAG supported development of the research questions, the inclusion and exclusion criteria for evidence, selection of terms to be included in the search strategy, data synthesis and interpretation.
2.1.		Research questions
The scoping review was guided by the following research questions:
1.		What is known about the barriers and enablers to healthcare professionals (HCPs) in primary care discontinuing antidepressants prescribed for CMDs?
2.		What interventions are described, tested and/or evaluated to facilitate HCPs in primary care to support patients to discontinue antidepressants prescribed for CMDs?
2.2.		Identifying relevant studies
2.2.1.		Eligibility criteria
The inclusion and exclusion criteria are presented in Table 1. The primary care setting was of interest as most antidepressants are prescribed in this setting.
2.2.2.		Search strategy
Relevant studies were identified by searching the following databases: MEDLINE, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Databases were searched from inception to January 2024. Search terms were developed by the research team which includes a pharmacist (SS), psychiatrist (ST), nurse (LB) and information specialist (MM), and members of the RAG. The search strategy was structured according to the Population, Concept and Context (PCC) approach 4; see Table 1. Searches were restricted to English language. No date or geographic restrictions were imposed on the search. The search strategy was adapted for each database; the searches for MEDLINE and Embase are provided as examples in Appendix 2.
2.3.		Study selection
Search results were downloaded into Zotero for de-duplication. Results were then exported into Microsoft® Excel to facilitate screening and then data extraction. Two reviewers (SS, BA) independently reviewed all titles and abstracts of article for full-text review against the eligibility criteria. If a study met the eligibility criteria, or if a decision could not be made based on the title and abstract alone, the full-text article was retrieved. All full-text articles were screened independently by SS and BA and any disagreements were resolved through discussion between the two reviewers with referral to a third reviewer (MM) where necessary.
Table 1
Inclusion and exclusion criteria according to Population, Concept and Context.
	Inclusion criteria	Exclusion criteria	
Population Context	Healthcare professionals
Primary care setting (inclusive of nursing/care homes); focus on the discontinuation of Focus on the discontinuation of antidepressants prescribed for non-mental antidepressants prescribed for mild-moderate depression, generalised anxiety	health conditions (e.g., chronic pain)
disorder (GAD), obsessive compulsive disorder (OCD), post-traumatic stress disorder
(PTSD), panic disorder and/or social anxiety disorder.	
Concept	Reporting barriers and/or enablers to HCPs discontinuing antidepressants, and/or interventions to facilitate HCPs to support patients through the discontinuation process.	
Publication	Original research (protocols, randomised controlled trial (RCT), quasi-experimental, Conference abstracts, systematic reviews, editorials, reviews, case reports, cohort study, qualitative and case studies); published in the English language.	and non-research letters.
Peer-reviewed studies	
a Protocol papers were included as they describe interventions that are being prepared for trial. For any eligible protocols, if the linked subsequent result paper was not retrieved by the search, a targeted search was conducted to identify one. The rationale is that both types of publication may provide valuable learning. For example, a protocol may describe in detail an intervention being tested whilst a results paper may provide less detail on the intervention (instead referring readers back to the protocol) but provide detail on efficacy and/or the barriers and enablers to intervention implementation.
b Systematic reviews were not eligible but if retrieved by the search were reviewed for the purpose of finding additional relevant studies (through scanning reference lists).

2.4.		Charting the data
A structured data extraction form on Microsoft®1 Excel was developed by the research team to extract and chart the following information from each included article; author(s), country, year of publication and study design, the reported barriers and/or enablers to HCPs in primary care discontinuing antidepressants, and key characteristics of interventions designed to facilitate them to support patients through the discontinuation process. Two reviewers (BA, SS) extracted and compared the data for all included studies.
2.5.		Summarising and reporting the results
The extracted data was summarised in tables, including one for study characteristics (Table 2), one for the reported barriers and enablers to HCPs in primary care discontinuing antidepressants (Table 3) and one for the key characteristics of interventions designed to facilitate them to support patients through the discontinuation process (Table 4). Accompanying the extracted data is a narrative synthesis of the key findings to ‘tell the story’ of the included studies.
3.		Results
3.1.		Search results
The search of the databases yielded a total of 386 studies. Four additional studies were identified through a targeted search and scanning of reference lists. Fig. 1 provides the PRISMA flow diagram of studies through the search and study selection process. After the removal of duplicates (using Zotero in the first instance, followed by additional manual checks), 253 articles were screened at the title and abstract stage. Review of title and abstract led to the exclusion of 223 studies and the retrieval of 30 studies for full-text screening. There was a 94.8 % agreement rate among reviewers (BA, SS) and Cohen’s k = 0.7, indicating substantial agreement. Thirteen studies were excluded at fulltext screening either because they did not report on barriers, enablers or an intervention or because the interventions were not targeted at primary care HCPs. Table 2 provides an overview of the 17 included studies.
3.2.		Study characteristics
Of the 17 included studies, nine reported barriers and/or enablers to HCPs in primary care discontinuing antidepressants prescribed for a CMD(26-34) and eight reported interventions to facilitate them in supporting patients to discontinue their antidepressant.’
3.2.1.		Studies reporting barriers and/or enablers
Studies reporting barriers and/or enablers were dated from 2010 to 2022 and most were carried out in the United Kingdom (n = 4),2’ with one study each from Australia, Ireland,' Belgium, Norway and the Netherlands. All but one of these studies were qualitative and gathered HCP’s views and experiences through semi-structured interviews or focus groups, while one study incorporated a quantitative element and used an online survey. Five of the studies were of GP perspectives only, two of GPs and patients, ′ one of GPs and nurses and one of GPs, GP assistants, nurses, community mental health team workers and psychotherapists. ' Three of the studies were about barriers and/or enablers to discontinuation in older patients/a nursing home setting specifically, ’ ’ whilst the remainder did not indicate a focus on a particular patient population.
3.2.2.		Studies reporting interventions
Studies reporting interventions were dated from 2012 to 2023 and were carried out in the Netherlands (n = 4), United Kingdom (n = 3) ’ ’ and Australia (n = 1). Four studies were Randomised Controlled Trial (RCT) protocols ,36,38,40 and two studies reported RCT results. ’ 1 Notably, both completed RCTs were conducted in the Netherlands. The final two studies were a cohort study and a qualitative study reporting the development of an intervention currently being tested in a RCT in the United Kingdom. Two RCTs reported interventions targeting GP and patients, ′ one targeting GPs, mental health nurses and patients, and one targeting GPs, nurse practitioners and patients.
All RCTs used antidepressant discontinuation at 6-12 months as their primary outcome measure, while one RCT used the Patient Health Questionnaire (PHQ-9) score for depressive symptoms at 6 months.

3.3.		
Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMSA) flow diagram.

Barriers and enablers to healthcare professionals discontinuing antidepressants
Table 3 provides an overview of the barriers and enablers to HCPs discontinuing antidepressants reported in the included studies.
3.3.1.		Barriers
Most studies reported that time constraints acted as a barrier to HCPs discontinuing antidepressants. ’ There was limited time to evaluate repeat prescriptions and short consultations limited opportunities to deprescribe or provide the extra support required to discontinue antidepressants. HCPs described repeat prescriptions as ‘easier’ to maintain than initiating discontinuation. Other organisational barriers included a lack of proactive medication reviews, deprescribing antidepressants not being a priority during medication reviews, limited follow-up policies and a decrease in review frequency following the first few months of treatment. ’ Two studies reported limited access to alternative support (e.g., psychological services) and the ‘fractured' care between GPs and psychiatrists as barriers to discontinuation.’
Fear of causing a patient to relapse was another commonly reported barrier to HCPs discontinuing antidepressants. ’ ’ ’ HCPs perceived it to be Tess risky’ to continue to prescribe antidepressants than potentially destabilising a patient. The lack of safety concerns about side-effects of long-term antidepressant use was also a barrier to discontinuation. ’ The reluctance from HCPs to ‘rock the boat’ in older patients was tied to their perception that this population was particularly ‘vulnerable’ to treatment changes and their fears of being blamed if the patient’s condition worsened. Relatedly, another barrier to discontinuation in this context was the influence of/pressure from nursing staff and relatives to continue prescribing antidepressants.■
There was a perception/expectation among HCPs that patients or relatives would broach the subject of discontinuation.’ ■ ′ This acted as a barrier, as HCPs assumed that if patients and their relatives did not question or initiate a change in their routine, they therefore wanted to continue treatment. HCPs noted that the responsibility to discontinue antidepressants rested with the initial prescriber. The relationship between the HCP and patient (or lack thereof) also acted as a barrier: a ‘weak' GP-patient alliance, lack in continuity of care, and inconsistent recommendations from different practitioners posed challenges to discontinuing antidepressants. ′
One study reported a lack of confidence in skills and knowledge with regards to antidepressant discontinuation acted as a barrier to HCPs broaching the subject of stopping with patients. A lack of clear advice in current clinical guidelines, specifically regarding to tapering regimes in long-term users, was reported as a barrier in studies conducted in the UK(31) and Australia. 3 HCPs noted that National Institute for Health and Care Excellence (NICE) guidance in the UK was limited and not applicable to ‘real' patients.
Patients' psychological dependence and reluctance, e.g., due to fear of relapse or unstable life circumstances, were barriers to

Table 2
Overview of included studies.
First author	Year	Country	Study design	Study setting/population	Study aim	
Studies reporting primary care healthcare professionals’ barriers and/or enablers to supporting patients through antidepressant discontinuation (n = 9)	
Bosman, R.	2016	Netherlands	Qualitative	Primary care; GPs, patients	To unravel the motivations of patients and GPs causing longterm antidepressant use and to gain insight into possibilities to prevent unnecessary long-term use.	
Bowers, H.	2019	United Kingdom	Qualitative	Primary care/community mental health; GPs, GP assistants, nurses, community mental health workers, psychotherapists	To identify, characterise and explain clinician factors that shape decision-making around antidepressant discontinuation in UK primary care.	
Dickinson,	2010	United	Qualitative	Primary care; GPs, patients	To explore the attitudes of older patients and their GPs to	
R.		Kingdom			taking long-term antidepressant therapy, and their accounts of the influences on long-term antidepressant use.	
Donald, M.	2021	Australia	Qualitative	Primary care; GPs	To explore general practitioners’ (GPs) insights about longterm antidepressant prescribing and discontinuation.	
Iden, K.R.	2011	Norway	Qualitative	Nursing homes; GPs, nurses	To explore decision-making on treatment with antidepressants among doctors and nurses in nursing homes.	
Johnson, C.	2017	United Kingdom	Qualitative	Primary care; GPs	To explore factors influencing GPs’ use of antidepressants and their doses to treat depression.	
Kelly, D.	2021	Ireland	Qualitative	Primary care; GPs	To explore GPs' perceptions and experiences of discontinuing antidepressants.	
Read, J.	2020	United	Qualitative &	Primary care; GPs	To assess GPs’ beliefs, knowledge and needs in relation to	
		Kingdom	quantitative		antidepressants and withdrawal.	
Van	2022	Belgium	Qualitative	Nursing homes; GPs	To explore the views of GPs working in nursing homes	
Leeuwen, Ε.					regarding discontinuation of long-term antidepressants in nursing home residents.	
Studies reporting interventions to facilitate HCPs to support patients through antidepressant discontinuation (n =	8)	
Bowers, H.	2021	United Kingdom	Qualitative (intervention development)	Primary care; GPs and patients	To develop a digital intervention to support practitioners in helping patients discontinue inappropriate long-term antidepressants.	
Johnson, C.	2012	United Kingdom	Cohort study	Primary care; GPs and patients	To review general practice patients prescribed the same antidepressant long-term (>2 years) and evaluate prescribing and management pre- and post-review.	
Kendrick, Τ.	2020	United Kingdom	Randomised controlled trial (Protocol)	Primary care; GPs, nurse practitioners and patients	To identify feasible, safe, effective and cost-effective ways of helping patients taking long-term antidepressants taper and stop treatment when appropriate.	
Muskens, E.	2013	Netherlands	Randomised controlled trial (Protocol)	Primary care; GPs and patients	To assess the effectiveness of a tailored recommendation to withdraw antidepressant treatment.	
Eveleigh, R.	2017	Netherlands	Randomised controlled trial			
Wallis, K.	2023	Australia	Randomised controlled trial (Protocol)	Primary care; GPs and patients	To determine the effectiveness of two multi-strategy interventions, RELEASE and RELEASE+, in supporting safe cessation of long-term antidepressants compared to usual care.	
Wentink, C.
Huijbers, M.	2019
2023	Netherlands
Netherlands	Randomised controlled trial (Protocol) Randomised controlled trial	Primary care; GPs, mental health nurses and patients	To investigate the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) added to supported protocolized discontinuation (SPD) compared with SPD alone to successfully discontinue long-term antidepressant medication use in primary care.	

Table 3
Reported barriers and enablers to HCPs discontinuing antidepressants.
First author/ Year/Country
Setting/Participants
Method of data Barriers to discontinuation collection
Enablers to discontinuation
Read, J. 2020. United Kingdom.
Primary care
66 GPs
• Average age 48.9
• 46 women/20 men
Online survey None reported.
Van Leeuwen, Ε.	Nursing homes	Semi-structured	• Influence of nursing staff and relatives	
2022. Belgium.	•		Urban (n = 10) and rural (n = 10) setting.
20 GPs
•		Average age 44.6
•		12 women/8 men	interviews	-		Pressure by nursing staff and relatives to continue antidepressants
-		Time and energy consuming to involve family and nursing staff
•		Reluctance to rock the boat
-		Fear of making things worse, being blamed/ feeling guilt
-		Limited alternatives available to antidepressants to support discontinuation (e. g., psychological counselling)
-		Changing routine and implementing a regular proactive review of antidepressants is difficult - if relatives do not question, they do not initiate.
• Deprescribing antidepressants is not a priority during a medication review.	
Donald, M.	Primary care	Semi-structured	• Lack of clear advice/guidelines regarding	
2021. Australia.	•		Urban (n = 11) and inner- regional (n = 11) practice setting
22 GPs
•		Average age 47 years
•		13 men/9 women	interviews	discontinuation in long-term users.
•		‘If it ain’t broke don’t fix it’ mentality - prescribing and repeat prescriptions are easier than initiating discontinuation.
•		Patient attitudes and reluctance - perception that the relationship pts have with their antidepressants is part of their identity.
•Weak GP-patient alliance (e.g., not always seeing ‘regular’ patients)	
Kelly, D. 2021.	Primary care	Semi-structured	
Ireland.	•		Urban (n = 6), rural (n = 3) and both (n = 1) practice setting
10 GPs
•		7 men/3 women	interviews	
•		Reluctance to ‘rock the boat’
- Fear of making things worse if the ‘wrong' decision is made to taper and a patient relapses.
•		Limited access to psychological services in the Irish healthcare system and ‘fractured' care between GPs and psychiatrists.
Bosman, R.	Primary care	Semi-structured	
2016. Netherlands.	•		Urban (GPs n = 18, patients η = 20) and rural (GPs n = 8, patients n = 18) practice setting
26 GPs
•		Aged 30-64
•		15 women/11 men	interviews	
•		Fear of relapse, especially for patients who have had previous relapses when attempting discontinuation.
•		Expectation that patients will contact GP if they want to discontinue their treatment (not clear it is their responsibility to initiate contact)
•		Perception that patients are psychologically dependent on their medication.
•		Limited follow-policies and not having time to evaluate repeat prescriptions.
Dickinson, R.	Primary care	Semi-structured
2010. United	· Focus on antidepressant use interviews
Kingdom.	in patients aged >75 years
10 GPs
• Aged 34-60
• 6 women/4 men
•		Reluctance to ‘rock the boat’
•		Lack of concern about side-effects of long-term antidepressant use, owing to lack of evidence of adverse effects.
•		Discontinuation requires extra time and support, and it is easier to ‘follow the path of least resistance’.
•		Pessimism about the curability of depression in patients whose circumstances are not stable.
•		Training or information, including guidelines/ protocol/flowchart/strategies on how to wean patients off, information about withdrawal effects, including what they are, incidence and differences between antidepressants. Most survey respondents wanted a form of online training (e.g. e-learning, webinar).
•		Alliance with nursing staff and relatives who support discontinuation, e.g., relatives spending more time with patient and nurses providing close follow-up throughout the withdrawal process.
•		Dementia, cognitive impairment and severe acute illnesses act as a trigger to review the appropriateness of continuing antidepressants; when the patient’s quality of life deteriorates, GPs no longer consider the antidepressants necessary to maintain quality of life.
•		Knowledge of the initial depressive disorder, the triggers, and why an antidepressant was initiated.
•		Strong GP-patient alliance that allows for joint reflection on why an AD was initiated
•		Standardised tools for identifying symptom change (K10)
•		Preparation and co-designed personalised discontinuation plan, including proactive relapse planning
•		Regular reviews during discontinuation
•		Evidence about adverse health outcomes of long-term use
•		Increased education, including patient handouts and support for GPs
•		Opportunities for benchmarking/auditing
•		Access to solutions/support beyond general practice - e.g., psychological support.
•		Referral options to psychological services such as counselling, talking therapies, and cognitive therapy.
•		Standardised clinical guidelines to assist them to provide evidence-based care.
•		Education on deprescribing antidepressants, including audit tools, inbuilt prompts on prescribing software to review a patient’s antidepressants, relapse rates and patient information on antidepressant deprescribing.
•		Change in practice policy so that repeat prescriptions are not an option for antidepressants.
•		Information regarding discontinuation, including tapering schedules, modules and treatment guidelines on ‘what you need to do’ during discontinuation.
•		Automatic prompts/warning when authorising repeat prescriptions for patients eligible to discontinue.
•		Supportive guidance during discontinuation; from GPs, mental health assistants or psychiatrists or psychologists, relatives and friends.
None reported.
(continued on next page)

First author/ Year/Country	Setting/Participants	Method of data collection	Barriers to discontinuation	Enablers to discontinuation	
Bowers, H.	Primary care/community	Focus groups	• Concern about destabilising patient - perception	• Computer systems that adequately prompt	
2019. United	mental health	and semi-	that it is ‘less risky’ to continue.	medication reviews so that patients do not get	
Kingdom.	21 GPs, 4 GP assistants, 7 nurses and 6 community mental health team workers and psychotherapists
• 22 women/12 men	structured interviews	•		HCPs lack of confidence, knowledge and skills.
•		Current (NICE) guidelines being unclear (especially regarding tapering regimes), limited, not accessible and not applicable to real patients.
•		Lack of continuity in care/different practitioners providing inconsistent recommendations.
•		Perceived need to be familiar with the patient to discuss stopping, and the idea that this responsibility lies with the initial prescriber.
•		Time constraints - in term of initiating and managing the stopping process (10-min consultation is not long enough)
•		Perception from HCPs that it is the patient’s responsibility to broach the subject (and if they don’t, HCPs assume they want to continue treatment)	Tost’ in the system.
•		Additional support from social workers, pharmacists, care coordinators and psychiatrists.
•		Support and information for HCPs and patients about how to discontinue.
•		Continuity of care/knowing the patient:
-		Involvement in initial prescription places responsibility on prescriber to initiate discussion about stopping.
-		Explaining to patients at initial prescription that stopping will be discussed at a later date.
-		Knowledge of the patients experience of antidepressants, their triggers for depression, why they started and how things have changed since initial prescription.	
Iden, K.R. 2011.
Norway.	Nursing homes 24 GPs and nurses
• Aged 30-70	Focus groups	•		Fear of exposing ‘vulnerable’ patients to treatment changes/disrupting ‘delicate balance’.
•		Influence of nursing staff
- Pressure by nursing staff to continue treatment.	None reported.	
Johnson, C.
2017. United Kingdom.	Primary care
28 GPs
•		Aged 33-60
•		14 women/14 men	Semi-structured interviews	•		Fear of relapse/‘causing more harm than good’
•		Pressures to maintain prescribing:
-		Patient wishes and fear of depression recurrence
-		Few perceived continuation problems (lack of safety concerns)
-		Lack of proactive medication reviews/decrease in review frequency following first few months of treatment.	None reported.	

discontinuation. · · ’ One study reported that patient attitudes were a barrier in that HCPs perceived the relationship some patients have with their antidepressants to be part of their identity.'
3.3.2. Enablers
There were fewer enablers to HCPs discontinuing antidepressants reported in the included studies than there were barriers (four out of nine studies did not report any enablers).
A key enabler was the availability of additional support, including from social workers, pharmacists and care coordinators, as well as referral services to psychological support, including counselling services, talking therapies and cognitive therapy.28,29, ’ In the nursing home setting, alliance with nursing staff and relatives was also noted as facilitating discontinuation, with relatives spending more time with patients and nurses providing close follow-up throughout the discontinuation process.
Most studies reported training, education and information for HCPs about discontinuing antidepressants as a key enabler. This included (standardised) clinical guidelines, tools for identifying symptom changes, tapering schedules, evidence about adverse health outcomes of long-term use, information about withdrawal effects, audit/bench- marking tools, and patient-facing information/hand-outs. ,28,29, A co-designed personalised discontinuation plan between the HCP and patient, including proactive relapse planning, was also noted as a facilitator to discontinuation.
The relationship between the HCP and patient acted as both a barrier and enabler. Continuity of care, involvement in the initial prescription and knowledge of the patients’ experiences of antidepressants (allowing for joint reflection on why the medicine was initiated and why it could be discontinued) were all reported as facilitators to discontinuation.27’28·31
Three studies reported that adjustments to prescribing systems to

generate automatic prompts would facilitate HCPs to discontinue antidepressants. For example, prompts for a medication review29" and alerts to HCPs about whether a patient was eligible to discontinue when authorising repeat prescriptions. One study reported that a change in practice policy, so that repeat prescriptions were not an option for antidepressants, would facilitate HCPs to discontinue antidepressants.
3.4.		Interventions to facilitate healthcare professionals to support patients through the discontinuation process
Table 4 provides an overview of the interventions to facilitate HCPs in primary care to support patients through the discontinuation process.
3.4.1.		Intervention characteristics
Most interventions comprised training and education for HCPs. ’ ’ ’ ‘Advisor for Health Professionals’ (ADvisor), a UK developed intervention, involved the provision of internet programmes to GPs and nurse practitioners. ADvisor included modules on: why reduce; broaching the subject; when to start tapering; reduction schedules for individual antidepressants; dealing with withdrawal symptoms; dealing with relapse; and printable pages on antidepressant reduction regimes. The ‘RELEASE(+)’ intervention, an Australian intervention, comprised the provision of a medicines information brochure, decision aid, tapering protocol, and additional prescribing support including audit and feedback for GPs. Two RCTs ′ conducted in the Netherlands provided tapering support materials to GPs. The Mindfulness-Based Cognitive Therapy plus Supportive Protocolized Discontinuation (MBCT + SPD) intervention included the provision of a decision aid covering the topics ‘Process of discontinuation’, “Expectations’, ‘Professional guidance’, ‘Current use’, ‘Environment’, and ‘Side effects‘(39).
RELEASE(+), ADvisor and MCBT + SPD are multi-strategy interventions that targeted both HCPs and patients. In addition to the

Table 4
Studies reporting interventions to facilitate HCPs to support patients to discontinue antidepressants.
First author/ Year/Country	Participants/Setting	Intervention characteristics	Intervention development (underpinning theory)	Method of data collection	Outcomes	Results	
Johnson, C. 2012.	GPs and patients (n =	GP review of condition	Ν/Α	Routine patient data	Review outcomes	Almost half of all study	
United	2849) in 78 urban	and medication, in		Pre- and post-review	were categorised as	patients were	
Kingdom.	primary care practices.	line with clinical		data were collected;	antidepressant	prescribed	
(Observational	Patients	guidelines		average	continued, stopped,	antidepressants long-	
cohort study)	Taking antidepressants for 2 years or more. Eligible patients were identified using a data extraction tool, in line with the National Institute for Health and Care Excellence (NICE) guidelines.	GPs were not provided with guidance or a sampling framework from which to select eligible patients - instead, GPs were allowed to prioritise patients for review they felt may benefit most.		antidepressant doses and changes in prescribed daily doses were calculated.
Onward referral to support services was recorded.	reduced, increased or changed.
Drug costs were calculated using British National Formulary 59 and Scottish Drug Tariff May 2010.	term. Reviewing long term patients resulted in one in four having their antidepressant therapy altered, providing reductions in prescribing and possible associated costs. Where follow-up reviews were performed, further additional reductions were made.
Note: 6.3 % (179/2849) patients were referred onwards to support services: 50.5 % NHS mental health, 23.1 % non-government organisations, 14.5 % NHS general medical and 11.8 % social and council services.	
Wallis, K. 2023.	GPs and patients in 28	RELEASE	Informed by the 3As	Questionnaires,	Primary outcome:	Ν/Α	
Australia. (RCT	primary care practices.	GPs receive printable	(Ask, Advise, Assist),	interviews	Antidepressant		
Protocol)	GPs
•		All or most general practitioners in included practices.
Patients
•		Sample size n = 653
•		18 years or older taking antidepressants for more than one year.	resources, education and training (including medicines information brochure, decision aid, tapering protocol), and tailored practice management software. Patients receive information about antidepressants, resources and an invitation to schedule and attend a review appointment with their GP.
Local community pharmacies near to intervention practices receive information about the study and long-term antidepressant use, seeking their support for patients discontinuing their antidepressants. RELEASE/ GPs receive additional prescribing support including audit and feedback.
Patients receive additional internet support (resources, messaging and e-mental health supports).	an evidence-based behaviour change model of brief interventions for patient-centred care. Qualitative interviews with GPs about their views on discontinuation, and a think-aloud study with patients with lived experience of longterm antidepressant use, informed intervention development.		discontinuation at 12 months (patient reported)
Secondary outcomes:
•		75 % antidepressant dose reduction at 12 months
•		Health related quality of life
•		Antidepressant side effects
•		Wellbeing
•		Discriminatory antidepressant withdrawal symptoms
•		Emotional numbing
•		Beliefs about antidepressants
•		Depressive symptoms
Anxiety symptoms
•		Antidepressant prescribing
•		Costs
•		Barriers and enablers to implementation.		
Wentink, C.	Mental health nurses,	Tapering support	Informed by a	Diaries,	Primary outcome:	The study did not	
2019.	GPs and patients in 36	materials, in addition	treatment protocol	questionnaires,	Antidepressant	demonstrate a	
Netherlands.	primary care practices.	to Mindfulness-Based	developed for	interviews.	discontinuation at 6	significant benefit of	
(RCT Protocol)	Patients	Cognitive Therapy	recurrent depression		months (patient	adding MBCT to SPD;	
&	• η = 119	(MBCT) added to	and patient feedback.		reported)	discontinuation rates at	
Huijbers, M.	• 18 years or older and	supported			Secondary	6-month follow-up	
2023.	taking	protocolized discontinuation (SPD)			outcomes:	were slightly higher in the SPD + MBCT group	
(continued on next page)

First author/ Year/Country	Participants/Setting	Intervention characteristics	Intervention development (underpinning theory)	Method of data collection	Outcomes	Results	
Netherlands.	antidepressants for 9	Patients and GPs are			• Relapse/recurrence	(44 %) than in the SPD	
(RCT)	months or longer.	provided with a decision aid (covering the topics ‘Process of discontinuation', ‘Expectations’, ‘Professional guidance’, ‘Current use’, ‘Environment’, and ‘Side effects’) and personalised tapering schedule based upon a discontinuation protocol.
Supported protocolized discontinuation (SPD)
Optional consultations offered by mental health nurses. Nurses receive a brochure, discontinuation protocol and guideline about how to organise consultations. The consultations focus on the topics in the decision aid, monitoring of withdrawal effects and discussing relapse prevention strategies.
Mindfulness-Based Cognitive Therapy (MBCT)
Eight group MBCT sessions are delivered by physicians in addition to a ‘silent practice day' in which patients receive all mindfulness practices without interaction or group discussions. Home practice take approximately 30-45 min a day using audioguided practices.			of depression and/ or anxiety
•		Depressive symptoms
•		Withdrawal
symptoms
•		Anxiety symptoms
•		Ruminative brooding
•		Wellbeing
•		Mindfulness skills
•		Self-compassion
•		Costs	group (33 %). Participation was low, both at the level of the GP practices (only a quarter of the invited practices participated), and at the level of patients of whom only one tenth responded to the study invitation. Of those who did respond to the invitation, less than half participated. Reasons included fear of recurring symptoms, pain, somatic comorbidity, social circumstances, or clinicians' advice against tapering.	
Kendrick, Τ.	GPs, nurse	Provision of ‘ADvisor’	Developed using	Questionnaires,	Primary outcome:	N/A	
2020. United	practitioners and	internet programmes	evidence (systematic	interviews	PHQ-9 score for		
Kingdom. (RCT Protocol)	patients in 134 primary care practices.
Patients
•		Sample size η = 402 (201 intervention and 201 control)
•		Taking antidepressants for more than one year for a first episode of depression or longer than two years for repeated episodes of depression.	‘ADvisor for Health Professionals’ includes internet modules on: why reduce; broaching the subject; when to start tapering; reduction schedules for individual antidepressants; dealing with withdrawal symptoms; dealing with relapse; a summary of the Advisor intervention for patients; and printable pages on antidepressant reduction regimes and sections of Advisor for patients.
‘Advisor’ for patients includes modules about	review, primary qualitative research) and theory (Behaviour Change Wheel, COM-B model of behaviour change, Normalisation Process Theory). Person-based approach; the development of guiding principles informed the planning phase of intervention development. Think aloud interviews provided views of the intervention in terms of usability and content.		depressive symptoms at 6 months.
Secondary outcomes:
•		Anxiety
•		Discontinuation of antidepressants (at 6 months, for at least 2 months)
•		Mental wellbeing
•		Antidepressant withdrawal symptoms
•		Antidepressant side effect
•		Patient satisfaction
•		Patient enablement
•		Quality of life
•		Costs		
Bowers, H. 2021.	Nurses (n = 2) and GPs	reducing and stopping;		Think-aloud	N/A	The development work	
United Kingdom.	(n = 17) in primary care.	how to reduce antidepressants;		interviews		highlighted a need for further guidance on	
(Qualitative - Intervention development)	•		11 women/8 men
•		Mean age 44	thinking about antidepressants; dealing with withdrawal				drug tapering schedules for practitioners and clarity about who is
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First author/ Year/Country	Participants/Setting	Intervention characteristics	Intervention development (underpinning theory)	Method of data collection	Outcomes	Results	
Muskens, Ε.	GPs and patients in 45	symptoms; I am worried about stopping; keeping well; thinking about what you value in life; and moving forward. In addition, patients receive three calls from a psychological wellbeing practitioner.
GP review of condition	N/A	Questionnaires,	Primary outcome:	responsible for broaching the subject of discontinuation.
The findings suggest that Advisor for Healthcare Professionals could work in practice, as the information is in easily and quickly accessible formats owing to time constraints in practice. The recommendation to	
2013.	primary care practices.	and medication, in		interviews	Antidepressant	discontinue was	
Netherlands.
(RCT Protocol)
&
Eveleigh, R.
2017.
Netherlands.
(RCT)	Patients
•		η = 146
•		Taking antidepressants for nine months or longer.	line with clinical guidelines
GPs receive patientspecific letters with the recommendation to discontinue the antidepressant.
Tapering support materials
GPs receive information on antidepressant tapering and discontinuation syndrome, including a detailed scheme for tapering for each patient, based on recommendations in the Dutch Multidisciplinary Guidelines for Depressive and Anxiety Disorders.			discontinuation during the 6-12- month follow-up (patient reported and CIDI 3.0).
Secondary outcomes:
•		Severity of psychological symptoms
•		Quality of life
•		Prevalence of discontinuation symptoms
•		Costs	ineffective and described as ‘counterproductive’; 10 of the 146 patients with inappropriate longterm use of antidepressants (across intervention and control groups) were able to successfully stop.
Half of the patients rejected the recommendation to discontinue, fuelled by fear of recurrence (56 %), relapse after previous discontinuation (12 %); presence of psychological symptoms (15 %); wanting a second opinion (12 %); and other unspecified reasons (6 %).	

components described above, all interventions provided patients with information and resources about antidepressant discontinuation. In addition, ADvisor provided telephone support for patients and RELEASE (+) provided messaging and e-mental health supports. In the MCBT + SPD trial, patients received MBCT sessions during the tapering process, as well as optional supportive consultations with mental health nurses to discuss topics such as side effects, withdrawal effects and relapse prevention strategies.
Two studies ’ described interventions intended to support GP review of patients' condition and medication in line with clinical guidelines. In a cohort study conducted in the UK, GPs were permitted to prioritise patients for review they felt might benefit most. The RCT conducted in the Netherlands provided GPs with patient-specific letters with the recommendation to discontinue an antidepressant, as well as a tapering schedule for each patient.
3.4.2.		Theory underpinning intervention development
Only two interventions were developed using behavioural science theory. ’ ADvisor was developed using evidence and behaviour and implementation theory (Behaviour Change Wheel, COM-B model of behaviour change, Normalisation Process Theory), in combination with in-depth qualitative interviews and focus groups with HCPs and patients. Barriers and facilitators from health professionals' perspectives identified in the literature and the development of guiding principles were used to inform intervention content. RELEASE(+) was developed using an evidence-based behaviour change model (Ask, Advise, Assist). Qualitative interviews with GPs and patients about their views on discontinuation also informed intervention development.
3.4.3.		Results of evaluated interventions
The two completed RCTs ‘ included in this review reported that their respective interventions did not lead to an increase in antidepressant discontinuation. Providing tapering support materials to HCPs and patients in addition to MBCT ‘demonstrated no significant benefit‘(39); discontinuation rates were slightly higher in the SPD + MBCT group (44 %) than in the SPD group (33 %). Engagement was low both at the level of the GP practices (owing to lack of time) and at the level of patients, owing to their fear of recurring symptoms, pain, somatic comorbidity, social circumstances, and clinicians' advice against tapering. Letters to GPs with a recommendation to discontinue antidepressants, plus tapering advice, was reported as ‘counterproduc- tive'(41); 10 of the 146 included patients (across intervention and control groups) successfully discontinued their antidepressants. The authors reported that this was a result of apprehensiveness regarding change on the part of participating GPs and patients; half of the study patients rejected the recommendation to discontinue, fuelled primarily by fear of condition recurrence (56 %).
The cohort study found that a prompted GP review of patients' condition and medication led to limited reductions in prescribing. Almost half of all study patients were prescribed antidepressants longterm and GP review of these patients resulted in one in four having their antidepressants altered. However, only 7 % (199/2849) stopped their antidepressant and only 12.8 % (366/2849) reduced their dose.
4.		Discussion
Provision of knowledge and skills to HCPs around antidepressant treatment and discontinuation, as well as access to alternatives to antidepressants to provide to patients, are both enablers that require addressing in an intervention to support primary care HCPs to discontinue antidepressants that are no longer needed. Insufficient time, lack of access to alternatives to antidepressants, fear of relapse and an expectation that patients initiate antidepressant discontinuation discussions are barriers reported in the research literature. Existing interventions to facilitate HCPs to discontinue antidepressants focus on provision of training, education and information regarding how to discontinue antidepressants, and some provide access to alternatives to antidepressants for patients, therefore addressing the identified enablers. However, existing interventions fail to address the barriers that HCPs report, which may explain the limited success in increasing antidepressant discontinuation.
In the absence of an intervention, HCPs report that there is a lack of clear advice available regarding how to discontinue antidepressants ’ and there is a need for guidelines to provide explicit instructions, for example tapering regimes, to guide HCPs to discontinue antidepressants. ’ ’ This contrasts evidence syntheses of barriers and enablers to deprescribing generally, in which prescribers indicate that they already have the knowledge and skills regarding how to deprescribe. However, this scoping review reflects findings of a realist review of opioid deprescribing interventions, which similarly reported that prescribers require guidelines. Most interventions included in this scoping review comprised of components that provide HCPs with information regarding how to deprescribe antidepressants. However, HCPs indicate that the source of this information should be the prescribing guidelines they are already familiar with and are accepted as gold standard. Whilst historically guidelines have not provided this level of guidance, new resources such as the 2024 The Maudsley Deprescribing Guidelines provide comprehensive advice, including step-by-step guidance regarding how to discontinue antidepressants. ' Whilst recognising that guidance and resources may address any knowledge and decision-making gaps (e.g., around tapering different antidepressants), provision of these resources does not address the key organisational barriers reported in the literature. Moreover, the extent to which guidelines such as The Maudsley Deprescribing Guidelines have been embedded into routine practice is yet to be determined.
Paradoxically, healthcare professionals may also associate guidelines with increased workload,4 which exacerbates time constraints and thus inadvertently acts as a barrier to the practice that the guideline advocates for. This is particularly relevant in the primary care context, where consultations are generally time limited. For example, in the UK consultations are limited to 10-min and patients do not always see the same HCP . This may explain why HCPs describe repeat prescriptions of antidepressants as ‘easier’ to maintain than initiating discontinuation - i.e., a lack of familiarity with a patient's condition and circumstances, limited consultation times and a lack in continuity of care produces a context in which discontinuation is counterintuitive. This is supported by HCPs reporting that involvement in the initial antidepressant prescription and an understanding of the patients’ experiences of antidepressants (allowing for joint reflection on why the medicine was started, how their circumstances have changed, and why it could be discontinued) provide optimal context for antidepressant discontinuation.27’28’31
Infrequent medication reviews contribute to sustained antidepressant use, which HCPs acknowledge and report as a barrier to discontinuation - e.g., a lack of proactive medication reviews and limited follow-up policies limit opportunities to deprescribe.' ’ However, simply prompting HCPs to review a patient's medication and condition is not enough to overcome these barriers. Two studies in this scoping review found this approach ineffective and even ‘counterproduc- tive’(41). One study reported that the ineffectiveness of their intervention was a result of the apprehensiveness regarding change on the part of participating GPs and patients; half of the study patients rejected the recommendation to discontinue, fuelled primarily by fear of condition recurrence (56 %). This aligns with the findings of a systematic review of barriers and enablers to benzodiazepine deprescribing in which prescribers reported anxiety about the potential adverse consequences for their patients and themselves.4
Insufficient time resulting in other activities being prioritised is a frequently reported barrier to deprescribing. Evidence included in this scoping review suggests that prescribers therefore continue to issue antidepressants as this is deemed less time consuming that deprescribing. However, continuing to prescribe a medicine is an active decision; the principles of good prescribing practice require prescribers to continue to evaluate the risks and benefits of continuing to prescribe not only during medication reviews but also when issuing repeat prescriptions. This evaluation may indicate deprescribing is necessary given up to 50 % of people prescribed antidepressants no longer have an evidence-based indication. Prescribers may risk litigation if the evaluation of risks and benefits is not undertaken prior to issuing further antidepressant prescriptions or if deprescribing is indicated but not actioned. Moreover, there is a wealth of literature from both the general deprescribing evidence base and for antidepressants that failure to discontinue medicines that have more risks than benefits before they cause harm leads to increased workload downstream. ’ This is particularly relevant to antidepressants, as the longer someone is taking them the more challenging and unpleasant the process of withdrawal can be. 3 Temporal discounting, whereby lack of action now is preferred over action later which is of increased burden, is a known barrier to deprescribing. A deprescribing intervention which was co-designed with HCPs in the UK hospital setting includes a component to address the same barrier. The component is a workshop which prompts HCPs to think about the pros and cons of not deprescribing, e.g. saving time now, with the pros and cons of deprescribing, e.g. saving more time in the future. 2
Healthcare professional's expectations that patients should initiate deprescribing discussions contradicts the literature regarding patients’ barriers and enablers to deprescribing. Whilst patients report that they want to be empowered to make deprescribing decisions, they also assume continued issuing of a medication by a HCP means the benefits outweigh the risks and that it is still indicated. Patients also report that they are apprehensive about seeking antidepressant deprescribing for fear of inadequate support from health services through the process.’ It is therefore incumbent on HCPs to be proactive with respect to antidepressant deprescribing. Several interventions targeting HCPs included in this scoping review were co-delivered with interventions targeting patients, such as provision of psychological support throughout the antidepressant withdrawal process. ’ The patient interventions respond to the concerns about lack of support; however, these will likely be ineffective unless HCP interventions address the breadth of their barriers and enablers to deprescribing antidepressants.
4.1.		Strengths and limitations
This is the first scoping review to investigate what is known about the barriers and enablers to HCPs in primary care discontinuing antidepressants prescribed for CMDs. In addition, the reported barriers and enablers are explored against interventions that facilitate HCPs in primary care to support patients to discontinue antidepressants prescribed for CMDs. This paper thus provides an evidence-base from which to design new interventions that address the reported barriers and enablers.
This study used a robust, up-to-date and comprehensive search strategy. However, the search was limited to English language studies only, which may not have supported inclusion of data from non-English speaking countries. Moreover, we did not include grey literature within the scope of our search which may have resulted in relevant evidence not published in the peer reviewed literature being excluded.
5.		Conclusion
Most interventions that aim to facilitate HCPs to support people to discontinue antidepressants focus on provision of knowledge and skills. Whilst these are enablers that require addressing, there are several barriers that have not yet been addressed by interventions, and which may explain the limited efficacy of evaluated interventions reported in this scoping review. Future interventions should be developed using appropriate theory, for example behaviour change or implementation theory, and address all barriers and enablers to HCPs supporting people to discontinue antidepressants. These may be co-delivered with patient- focused interventions to ensure appropriate support through the process of antidepressant discontinuation.
CRediT authorship contribution statement
Bethany Atkins: Writing - review & editing, Writing - original draft, Visualization, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Michelle Maden: Writing - review & editing, Methodology, Data curation. Linda Birt: Writing - review & editing. Samuel Tromans: Writing - review & editing. Zoe Swithenbank: Writing - review & editing. Olivia Rose Kersey: Writing - review & editing. Pam Smith: Writing - review & editing. Sion Scott: Writing - review & editing, Writing - original draft, Supervision, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Funding
This project was supported by Research Capability Funding from National Health Service (NHS) Norfolk and Waveney Integrated Care Board (OM70555695; Scott; NWICB RCF2023/24).
Competing interests
The authors declare that they have no competing interests.
Acknowledgements
We would like to thank Ceri Steele and John Halliwell for their support on this study. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to the Author Accepted Manuscript version arising from this submission.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi. org/10.1016/j.sapharm.2025.02.004.
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