WiserAD: The Effect of a Structured Online Intervention on Antidepressant Deprescribing in Primary Care

Study Overview
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Brief Summary
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The use of antidepressants (ADs) is increasing globally, including within Australia, which has one of the highest rates of AD prescribing. Despite clear benefits for many people, there is reason to believe that the ongoing use of these medications is often not properly monitored or stopped (deprescribed) when a person returns to better Mental health. This trial sets out to test how well an online support tool (WiserAD) can help patients and their general practitioner to manage the careful and appropriate reducing and stopping of antidepressants, in primary care patients.

Detailed Description
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Antidepressants (ADs) have significantly improved the health and wellbeing for very many people and their success in enabling those with depression to retain their quality of life has undoubtedly led to their widespread use around the globe. However, the success of ADs has also led to a significant and unnecessary clinical and economic burden on the healthcare system and patients, through over prescribing, most often in cases when they are no longer of therapeutic use. Such inappropriate medicine use (defined as use that is going against clinical guidelines) is a significant financial and clinical challenge for healthcare providers globally. Recent figures show that alongside the US, UK and parts of Northern Europe, Australia now has one of the world's highest AD prescribing rates with a total cost of over $200 million per year. In 2015-2016 alone there were more AD prescriptions than people: 24.72 million - up 20% since 2012. Significantly, much of this this is due to an excess of long term users rather than an increase in the number of people being newly diagnosed with major depressive disorder (MDD) or other disorders for which ADs are prescribed (e.g. anxiety). In a recent study by this group a cohort of almost 800 primary care patients with depressive symptoms showed that only 15% of long term users satisfied clinical criteria for long term AD use. There is relatively little research that explores the long term effects of AD use but there are indications that it can be harmful. In many cases, long term use can be linked to a range of severe side effects including increased risk of cardiovascular events, gastrointestinal bleeding and diabetes. Psychological dependence is another problem facing users and stems from a perceived need to take ADs for fear of a relapse. That fear, shared by doctors, explains why AD use is unnecessarily protracted, even though it may undermine patients' autonomy and resilience, becoming less likely to self-manage or willing to stop their AD medication. Crucially, the evidence for relapse comes primarily from studies on AD users for whom guidelines recommend continued treatment (those who meet diagnostic criteria for moderate to severe major depressive disorder and have been receiving AD treatment for less than 12 months). In those with milder symptoms epidemiological research suggests that long-term AD use does not increase the likelihood of relapse and that that inappropriate long-term AD users can safely cease their medication. These findings are supported by a randomised controlled trial of AD cessation for primary care patients without current depression which showed a much smaller difference in relapse than previously thought. Limiting AD use only to cases in which it is clinically indicated is in line with quality prescribing and will help to reduce costs and associated adverse events as well as the potential benefit of improving long-term mental health outcomes for patients. Although they are not addictive research has shown that ADs are more difficult to cease than other medications and previous studies have demonstrated limited success in deprescribing trials of antidepressants compared to other medications suggesting that a more intensive, patient-focused intervention is required to support successful de-prescribing. The WiserAD study will test whether a novel, structured approach to deprescribing antidepressants is more effective than usual practice in enabling GPs to help patients cease (or decrease) their AD medication whilst maintaining their mental health and wellbeing.

Official Title
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WiserAD: A Randomised Trial of a Structured Online Intervention to Promote and Support Antidepressant Deprescribing in Primary Care.

Conditions
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Depression

Intervention / Treatment
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* Behavioral: WiserAD
* Behavioral: Attention control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years Stable on AD for >=12m (no depressive episodes) No history of recurrent depression Sufficient English language proficiency to provide informed consent No or mild depressive symptoms (PHQ-9) Low risk of Suicide or Self-harm Agree to consider reviewing their AD use Agree to be randomized into the study Willing to provide informed consent Exclusion Criteria: Moderate/severe depressive symptoms (PHQ-9 ≥10) at study entry or history of severe or recurrent depression Experienced a major life event in the past 3 months, or foresee one occurring in the next 3 months (e.g. trauma, grief, loss of role, major health issue, financial crisis) Continued AD use indicated for other condition (e.g. anxiety) Currently prescribed a non-SSRI/SNRI AD, antipsychotic, or mood stabiliser No internet access. Exclusion Criteria: Those currently experiencing a major life event in the next 3 months Currently using ADs for any other health condition (other than depression) Currently using non-SSRI or SNRI ADs, antipsychotics, or other mood stabiliser medication Have no daily access to the internet

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single blind, parallel-arm, randomised controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Participants will be provided with a personal login code for the study web portal via automated email and encouraged to complete the initial components of the intervention which seek to determine participants' current support and management strategies and help them to understand their specific antidepressants. They will then complete the third component which contains three sub-sections to assist in creating a personal plan to help them cease their ADs: i) Management strategies for withdrawal symptoms and opportunities to discuss the plan with their GP or trusted Mental health worker; ii) Selecting a start time to begin tapering; iii) Print out of the personalised action plan to keep and share with supportive family and/or friends. Participants will also be required to complete a daily check-in through the portal which will check current symptoms and highlight any negative changes in emotional wellbeing, they will also receive texts reminders to complete these tasks. | Behavioral: WiserAD<br>* See Arms<br>|
| Experimental: Usual care - Attention Control<br>Participants allocated to the treatment as usual group will receive usual care plus attention control which comprises a link to the AD factsheet within the BeyondBlue website. This provides education material relevant to the participants' enrolment in the study but they will not be advised to cease or continue with their medication. GPs will not be advised of the participants allocated to this treatment arm. | Behavioral: Attention control<br>* See Arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients successfully ceasing ADs at 6-months post baseline | Successful cessation is defined as no AD use and the absence of clinically significant depressive symptoms | Primary outcome is at 6-months post baseline. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Health Questionnaire (PHQ-9) | 9-items, 4-point likert scale ranging from 0 (not at all) to 3 (nearly every day). Total scores range from 0-27 with higher scores indicating higher levels of depressive symptoms. | Baseline, 3-, 6-, 12-, 18- and 24-months. | 
| General Anxiety Disorder-7 (GAD-7) | 7-items, 4-point likert scale ranging from 0 (not at all) to 3 (nearly every day). Total scores range from 0-21 with higher scores indicating higher levels of anxiety. | Baseline, 3-, 6-, 12-, 18- and 24-months. | 
| Patient Activation Measure (PAM) | 13-item measure that assesses patient knowledge, skill, and confidence for self-management. 4-point likert scale ranging from 1 (disagree strongly) to 4 (agree strongly) plus a not applicable option. Total PAM score is the raw score is divided by the number of items answered (excepting non-applicable items) and multiplied by 13. Then, this score is transformed to a scale with a theoretical range 0-100. | Baseline, 3-, 6-months. | 
| Assessment of Quality of Life (AQoL-4D) | 12-item, likert scale (options differ depending on question). Scoring is for 4 dimensions (Independent Living, Mental Health, Relationships, Senses) | Baseline, 3-, 6-, 12-, 18- and 24-months. | 
| Resource Use Questionnaire (RUQ) | Study specific questionnaire measuring health resource use (e.g. doctor visits, medications taken). | Baseline, 3-, 6-, 12-, 18- and 24-months. | 
| Signs and Symptoms | Study specific questionnaire asking about common AD side effects. Participants can enter up to 3 text response answers about any effects they have experienced. | 3-, 6-months. | 
| Beliefs About Medication Questionnaire (BMQ) Antidepressant version | 18-items, 5-point likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). Scored across four domains (Specific Beliefs about Antidepressants - Necessity, Specific Beliefs about Antidepressants - Concerns, General beliefs about medicine - Overuse, General beliefs about medicine - Harms). | Baseline, 3-months. | 
| User Engagement Scale-Short Form (UES-SF) | 12-items, 5-point likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). An overall engagement score can be calculated by adding all of the items together and dividing by twelve. | 3- and 6-months. | 
| Accountability Measurement Tool (AMT) | 12-items, 5-point likert scale ranging from 1 (Strongly disagree) to 5 (Strongly agree). | 3- and 6-months. | 
| Medical Benefit Scheme (MBS) and the Pharmaceutical Benefit Scheme (PBS) data | Government collected data re: prescriptions and health service use for the duration of time in the study. | Provided at completion of the study (patient data collected for duration of time in study - up to 2 years). | 
| Proportion of patients successfully ceasing ADs at 6-months post baseline | Successful cessation is defined as no AD use and the absence of clinically significant depressive symptoms. | Measured at 3-, 12-, 18-months to track deprescribing adherence. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deprescribing, Antidepressant, Tapering, Primary Care