The Antidepressant Advisor Study

Major Depressive Disorder Clinical Trial

— ADeSS  

Official title:

The Antidepressant Advisor: A Decision Support System for UK Primary care-a Feasibility Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03628027
• Other study ID #: PB-PG-0416-20039
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2018
• Est. completion date: July 2021

Study information

• Verified date: July 2020
• Source: King's College London
• Contact: Roland Zahn
• Phone: 020 7848 0348
• Email: adess[@]kcl.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Antidepressant Advisor Study is a feasibility study to develop and probe the feasibility of a computerised decision support tool for GPs to prescribe antidepressant treatments. The study will use an algorithm to support GPs in their prescribing decisions for patients who have previously not responded to first-line antidepressants. Another group of GPs will prescribe as usual without the algorithm so that the effectiveness of the tool can be assessed, in terms of patient recovery. The aim of the study is to design a support tool which can aid GPs to prescribe the most effective treatment option for the patient so that they have increased likelihood of improvement in depression. A further aim of the study is to assess GP adherence and satisfaction with the tool so that modifications can be made that would improve the usability of the tool in future trials.

Description:

To address the urgent need for user-friendly decision support for antidepressant choices in UK primary care, the investigators will probe a specifically tailored innovative tool advising GPs on patients who have not responded to first-line treatments. Despite one promising US study, there is no such tool available in the UK. The US study was based in a private GP setting and employed now outdated treatment algorithms. In contrast, the treatment algorithm implemented in the current decision support tool is based on National Institute for Health and Care Excellence (NICE) guidelines including the latest health technology appraisals. The investigators have further gained the support of the leading UK provider of primary care electronic record systems (EMIS group: >3000 GP practice users) who will develop the software implementation of the algorithm as an add-on tool to their widely employed software.

Considering complex intervention guidance, the study is designed as a feasibility study to provide estimates of the following unknown variables needed to plan a subsequent larger trial: lost to follow-up and recruitment rates, GP satisfaction with the tool, impact on health service use, and standard deviations on our planned primary outcome measure on the self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR16) for a subsequent trial. The investigators will use a single-blinded parallel group cluster-randomised controlled trial design with at least 8 GPs across 8 practices (one per practice) being randomised supported by the Clinical Research Network (CRN) to two arms: 1) Usual care of patients with depression with no computerised decision support, 2) Using the novel computerised decision support tool to assist with antidepressant choices.

The investigators will recruit 8-20 GPs in 8-20 different practices to avoid communication between GPs, each contributing approximately 10 study patients. The EMIS eligibility tool (see below) will identify potential participants by screening for antidepressant and problem history. Blinded practice staff/CRN will ask all eligible patients for consent for contact. Patients will fill in an electronic version of the self-report version of the Primary Care Evaluation of Mental Disorders (PRIME-MD) and provide electronic consent for this. Alternatively, participants will be called to answer the questions over the phone and provide oral consent. Other patients will prefer receiving a mailed printed questionnaire and provide written consent. PRIME-MD has been validated against clinical diagnoses of current major depressive and anxiety disorders, as well as alcohol abuse according to DSM-IV criteria and will be modified to screen for drug abuse and anxiety disorders may be dropped from the screening as they are not exclusion criteria and will be assessed in the in-depth assessment. Patients will further complete self-report versions of the WHO Composite International Diagnostic Interview (CIDI) screening scale for bipolar disorder and 3 screening questions validated in the investigators' group to exclude schizophrenia. Further, the investigators will ask about the inclusion and exclusion criteria for the study, because the information recorded on EMIS is not always complete and does not always include a patient's history with previous GP surgery for example. Eligible patients will be seen for an in-depth assessment by the study research associate (RA) where she will take written informed consent.

2.1.2 Data collection and Assessment for patients meeting the pre-screening criteria

As in the investigators' previous work, the RA will be closely supervised and trained, establishing sufficient inter-rater reliability on semi-structured interviews with the PI before carrying out assessments independently. Apart from the outcome measures, the in-depth assessment will include measuring past subthreshold hypomanic symptoms, and perceived credibility of and expectancy towards treatment using a dedicated questionnaire, and a detailed clinical evaluation whilst accessing patients' EMIS records including:

• Treatment history

• Medical history

• Age at onset, episode duration and number, illness duration

• International Neuropsychiatric Interview (MINI) suicidality screen

• DSM5 Structured Clinical Diagnostic Interview

• Addenbrooke's Cognitive Examination-R in patients over 50 to detect early Alzheimer's disease

• Young Mania Rating Scale The results of the assessment will be shared with GPs and patients. This will also allow the investigators to use the Maudsley Staging Method to compare the level of treatment resistance between treatment groups prior to entry into the study as a potential confounder. Patients who meet the inclusion/exclusion criteria will subsequently be seen by their GP who initiates and monitors treatment using EMIS. The decision whom to include will not be made by the GPs to ensure against different selection biases in the different treatment arms. The RA will be blinded to the intervention arm that a GP was randomised to, in order to prevent the RA from making biased inclusion/exclusion decisions. The RA will communicate inclusion/exclusion decisions to patients and will draft a short report to their GP. The RA will seek the Chief Investigator's advice on inclusion/exclusion questions without telling him which GP the patient was referred from. Should the RA become unblinded accidentally or for some other reason, this would be noted in the case record file, but the patient would be retained in the study. On the second and final RA visit 15-18 weeks after the baseline assessment, outcome measures and Young Mania Rating Scale will be repeated and the Longitudinal Interval Follow-up Interview will be used to determine remission, its psychiatric status rating scale will be used at baseline for comparison. After being enrolled, patients, who have no smartphone, receive a mobile smart phone to access a secure patient app (developed as part of the proposal which will communicate via secure email with GPs) to prompt them to enter weekly (changing the usual two week time interval to one week and using the Maudsley modified version) PHQ-9 ratings (chosen also because it has no licencing restrictions), to report hypomanic symptoms, fill in a validated self-report side effects scale (Frequency, Intensity, and Burden of Side Effects Rating (FIBSER), and enter medication (including opting in for a reminder function), as well as asking about self-blame-related action tendencies such as hiding. The app will be based on an adaptation of similar mood tracking apps developed by our BRC. Alternatively, ratings and medication compliances will be asked about at weekly intervals via post or phone which will be recorded in the case file.

Main objectives of this study

1. To develop the first computerised decision support tool for antidepressant treatment in UK primary care

2. To probe the feasibility of a clinical trial to assess the tool's efficacy by

1. estimating lost to follow-up rates

2. estimating GP and patient adherence to prescribed medications

3. determining the number of GP practices willing to recruit patients for the study (determined by the CRN who will approach all practices in the participating CCGs)

4. estimating the recruitment rates per GP

5. estimating GP satisfaction

3. To provide standard deviation estimates and intra-class correlation coefficients per GP for computing effect size estimates for improving treatment outcomes in preparation of larger subsequent trials

4. To collect health economic estimates of changes in service use associated with the new tool (including psychiatric referrals to mental health teams and/or the study psychiatrist).

As soon as possible after their baseline in-depth assessment, eligible patients will undergo treatment over 14 weeks with their GPs which allows 3 weeks for determining sufficient treatment response at low and high dose of each of the two different recommended medications and 1 week for cross-tapering before step 1 and step 3. The final assessment by the RA will take place 15-18 weeks after the baseline assessment. Patients' participation will therefore last for approximately 15-18 weeks. Deviations from this time will occur due to scheduling difficulties and will be recorded. Time in the study will be used as a covariate in secondary data analyses.

GPs will be randomised into two groups, asking each GP to enroll approximately 8-11 participants each, adding more GPs if necessary. The study aims to recruit 86 participants assuming the same lost to follow-up rate as in the US trial (18%), resulting in a final sample size of 70 (35 in each group as recommended). This will enable the investigators to estimate the lost to follow-up rate within a 95% confidence interval of +/-8%. Because the comparable previous trial did not provide effect size estimates, this study has been designed to provide means and standard deviations, as well as confidence intervals for measures of change on the primary outcome measure (QIDS-SR16) in n=35 per group as recommended for feasibility trials.

Double data entry will be employed. Categorical outcomes (e.g. lost to follow-up rate) will be described using appropriate summary statistics. The QIDS-SR16 and other continuous outcomes will be summarised at baseline and final assessment time points to obtain means and standard deviations for a larger trial sample size calculation, with the GP intra-class correlation calculated for the outcome variable using one-way random effects analysis of covariance (adjusted for baseline). The investigators plan to do a preliminary analysis of the difference between the groups, as far as possible using the intention to treat principle. This analysis will be identified as preliminary and underpowered when published. The outcomes measured at baseline and follow-up only, such as the QIDS-SR16, will be analysed using robust linear regression to account for clustering within GP. Continuous outcomes measured weekly will be analysed using mixed linear regression models with an intercept for GP to account for clustering. Both types of models will include treatment group as a covariate, in order to estimate differences between the two intervention groups, and will adjust for the baseline measure of the outcome where appropriate. The investigators do not expect missing baseline data, however, any such missing data will be imputed using mean imputation. Missing data in the weekly outcomes will be accounted for under the missing at random assumption by using the maximum likelihood algorithm to fit the mixed models. The investigators may consider multiple imputation for outcomes measured only at follow-up if post-randomisation adherence variables can be quantified and are related to having missing outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 86
• Est. completion date: July 2021
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• age 18 years +

• at least moderately severe major depressive syndrome on PHQ-9 (score 15 +)

• no plans to change GP practice

• able to complete self-report scales orally or in writing

• no previous prescription of mirtazapine or vortioxetine

• early treatment resistance as defined by 1) current or recent prescription (in the last 2 months) of any of the following antidepressants: citalopram, fluoxetine, sertraline, escitalopram, paroxetine, venlafaxine, or duloxetine AND 2) previous prescription of at least one other antidepressant out of the same list.

Exclusion Criteria:

• inability to consent to study

• unstable medical condition

• currently receiving specialist psychiatric treatment

• high suicide risk (MINI suicidality screen)

• past diagnosis of schizophrenia or schizo-affective disorder

• current psychotic symptoms (3 clinical screening questions)

• bipolar disorder

• currently at risk of being violent

• drug (modified PHQ) or alcohol abuse (PHQ) over last 6 months

• suspected central neurological condition

• pregnancy or insufficient contraception in women of childbearing age

• breastfeeding or within 6 months of giving birth in women of childbearing age

• both escitalopram and sertraline have already been prescribed

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Device:
• Computerised decision support algorithm
The algorithm is integrated into the EMIS computer system used by GPs. The algorithm advises on which antidepressants should be prescribed based on a patient's treatment history.

Locations

Country	Name	City	State
United Kingdom	King's College London, IoPPN	London

Sponsors (4)

Lead Sponsor	Collaborator
King's College London	D'Or Institute for Research and Education, EMIS PLC, NHS Lambeth Clinical Commissioning Group

Country where clinical trial is conducted

United Kingdom, 

References & Publications (5)

Kurian BT, Trivedi MH, Grannemann BD, Claassen CA, Daly EJ, Sunderajan P. A computerized decision support system for depression in primary care. Prim Care Companion J Clin Psychiatry. 2009;11(4):140-6. doi: 10.4088/PCC.08m00687. — View Citation

Lythe KE, Moll J, Gethin JA, Workman CI, Green S, Lambon Ralph MA, Deakin JF, Zahn R. Self-blame-Selective Hyperconnectivity Between Anterior Temporal and Subgenual Cortices and Prediction of Recurrent Depressive Episodes. JAMA Psychiatry. 2015 Nov;72(11):1119-26. doi: 10.1001/jamapsychiatry.2015.1813. — View Citation

NICE. Depression: The treatment and management of depression in adults. The British Psychological Society and The Royal College of Psychiatrists; 2010.

Rollman BL, Hanusa BH, Lowe HJ, Gilbert T, Kapoor WN, Schulberg HC. A randomized trial using computerized decision support to improve treatment of major depression in primary care. J Gen Intern Med. 2002 Jul;17(7):493-503. — View Citation

Symons L, Tylee A, Mann A, Jones R, Plummer S, Walker M, Duff C, Holt R. Improving access to depression care: descriptive report of a multidisciplinary primary care pilot service. Br J Gen Pract. 2004 Sep;54(506):679-83. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Recruitment Rate	Rate at which patients are recruited to the study	Through study completion, an average of 16 months
Other	Lost to Follow-up Rate	Rate at which patients are lost to follow-up	Through study completion, an average of 16 months
Other	Adverse Event Rate	Grade and rate at which adverse events occur	Through study completion, an average of 16 months
Other	Helpfulness, ease of use and workload of intervention using King's GP Satisfaction Measure	Average GP satisfaction. Includes recommendation for future clinical use, and opinion on usefulness to patient care. Subscale ranges-Q1: 0 - 11, Q2: 0 - 6 (higher score indicates more improved care), Q3: 0 - 6 (higher score indicates higher workload), Q4: 0 - 6 (higher score indicates higher helpfulness), Q5: 0 - 6 (higher score indicates higher workload), Q6: 0 - 6 (higher score indicates easier to use), Q7: 0 - 6 (higher score indicates more improvement in care), Q8: 0 - 6 (higher score indicates better than other tools), Q9: 0 - 6 (higher score indicates less likelihood to ignore tool), Q10: 0 - 6 (higher score indicates more strongly recommend)	Through study completion, an average of 16 months
Other	GP Adherence to Algorithm	Assessed for each patient by trial clinician, from 0 (none of the recommended steps implemented) to 3 (fully implemented)	Week 16
Other	Service Use (EMIS)	Information taken from EMIS, including psychiatric referrals, referrals to study psychiatrist, time to psychiatric referral	Week 16
Other	Adult Service Use Schedule (AD-SUS)	Assessed on routine validated KCL questionnaire. Subscale ranges: Q1: 0 (no) 1 (yes), Q2: continuous number, Q3: 0 (no), 1 ( yes), Q4: continuous number, Q5: 0 (no), 1 (yes), Q6: text answer, Q7: continuous number	Week 16
Other	Euroqol Quality of Life Measure (EQ-5D-3L)	Change from baseline quality of life. Assessment of cost-effectiveness of intervention. Visual analogue question range: 0 - 100. Higher score indicates better perceived health.	Week 16
Other	Average % Patient Adherence (EMIS)	Information taking from EMIS including prescribing records	Week 16
Other	Social and Occupational Functioning Assessment Scale (SOFAS; DSM-V)	Change from baseline psychological functioning	Week 16
Other	Maudsley Visual Analogue Mood Scale	Change from baseline mood. Total scale range: 0 - 300. Higher scores indicate more improvement in mood.	Week 16
Other	Patient Adherence	Information taken from EMIS including % of attended GP visits out of total scheduled number	Week 16
Other	Frequency, Intensity and Burden of Side Effects Rating (FIBSER)	Average score for medication side effects. Each subscale range: 0 - 6. Higher scores indicate more burdensome side effects.	Weekly for 16 weeks
Other	Average % Patient Adherence (Mobile App)	Adherence to prescribed antidepressants	Weekly for 16 weeks
Other	Average Maudsley Modified Patient Health Questionnaire (PHQ-9)	Average depression score over last 2 weeks. Total scale range: 0 - 21. Higher scores indicate more depressive symptoms.	Weekly for 16 weeks
Primary	Self-Rated Quick Inventory of Depressive Symptomatology (QIDS-SR16)	Change from baseline depressive symptoms (not primary outcome for this feasibility study, only for full trial, primary feasibility outcomes are listed from 6 onwards). Total scale range: 0 - 48. Higher score indicates more change in depressive symptoms.	16 weeks
Secondary	Montgomery Asberg Depression Rating Scale (MADRS)	Change from baseline depressive symptoms. Total scale range: 0 - 60. Higher score indicates more change in depressive symptoms.	16 weeks
Secondary	Clinical Global Impression	Change from baseline severity Total scale range: 1 - 7. Lower score indicates more improvement in symptoms.	16 weeks
Secondary	Generalised Anxiety Disorder (GAD-7)	Change from baseline anxiety symptoms used in the NHS. Total scale range: 0 - 21. Higher score indicates more change in anxiety symptoms.	16 weeks
Secondary	Body Mass Index (BMI)	Change from baseline healthy weight. Total range: 12 - 42. Higher score indicates more change in BMI.	16 weeks