Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2023

Open Access 01-12-2023 | Antidepressant Drugs | Study protocol

RELEASE (REdressing Long-tErm Antidepressant uSE): protocol for a 3-arm pragmatic cluster randomised controlled trial effectiveness-implementation hybrid type-1 in general practice

Authors: Katharine A. Wallis, Maria Donald, Mark Horowitz, Joanna Moncrieff, Robert S. Ware, Joshua Byrnes, Karen Thrift, MaryAnne Cleetus, Idin Panahi, Nicholas Zwar, Mark Morgan, Chris Freeman, Ian Scott

Published in: Trials | Issue 1/2023

Login to get access

Abstract

Background

Many people experience withdrawal symptoms when they attempt to stop antidepressants. Withdrawal symptoms are readily misconstrued for relapse or ongoing need for medication, contributing to long-term use (> 12 months). Long-term antidepressant use is increasing internationally yet is not recommended for most people. Long-term use is associated with adverse effects including weight gain, sexual dysfunction, lethargy, emotional numbing and increased risk of falls and fractures. This study aims to determine the effectiveness of two multi-strategy interventions (RELEASE and RELEASE+) in supporting the safe cessation of long-term antidepressants, estimate cost-effectiveness, and evaluate implementation strategies.

Methods

Design

3-arm pragmatic cluster randomised controlled trial effectiveness-implementation hybrid type-1. Setting: primary care general practices in southeast Queensland, Australia. Population: adults 18 years or older taking antidepressants for longer than 1 year. Practices will be randomised on a 1.5:1:1 ratio of Usual care:RELEASE:RELEASE+. Intervention: RELEASE for patients includes evidence-based information and resources and an invitation to medication review; RELEASE for GPs includes education, training and printable resources via practice management software. RELEASE+ includes additional internet support for patients and prescribing support including audit and feedback for GPs. Outcome measures: the primary outcome is antidepressant use at 12 months self-reported by patients. Cessation is defined as 0 mg antidepressant maintained for at least 2 weeks. Secondary outcomes: at 6 and 12 months are health-related quality of life, antidepressant side effects, well-being, withdrawal symptoms, emotional numbing, beliefs about antidepressants, depressive symptoms, and anxiety symptoms; and at 12 months 75% reduction in antidepressant dose; aggregated practice level antidepressant prescribing, and health service utilisation for costs. Sample size: 653 patients from 28 practices. A concurrent evaluation of implementation will be through mixed methods including interviews with up to 40 patients and primary care general practitioners, brief e-surveys, and study administrative data to assess implementation outcomes (adoption and fidelity).

Discussion

The RELEASE study will develop new knowledge applicable internationally on the effectiveness, cost-effectiveness, and implementation of two multi-strategy interventions in supporting the safe cessation of long-term antidepressants to improve primary health care and outcomes for patients.

Trial registration

ANZCTR, ACTRN12622001379707p. Registered on 27 October 2022.
Literature
1.
2.
Kjosavik SR, Gillam MH, Roughead EE. Average duration of treatment with antidepressants among concession card holders in Australia. Aust N Z J Psychiatry. 2016;50(12):1180–5.PubMed
3.
Brett J, Karanges EA, Daniels B, Buckley NA, Schneider C, Nassir A, et al. Psychotropic medication use in Australia, 2007 to 2015: changes in annual incidence, prevalence and treatment exposure. Aust N Z J Psychiatry. 2017;51(10):990–9.PubMed
4.
5.
Hengartner MP. How effective are antidepressants for depression over the long term? A critical review of relapse prevention trials and the issue of withdrawal confounding. Ther Adv Psychopharmacol. 2020;10:2045125320921694.PubMedPubMedCentral
6.
7.
8.
Malhi GS, Bell E, Bassett D, Boyce P, Bryant R, Hazell P, et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry. 2021;55(1):7–117.PubMed
9.
Rothmore J. Antidepressant-induced sexual dysfunction. Med J Aust. 2020;212(7):329–34.PubMed
10.
Bala A, Nguyen HMT, Hellstrom WJG. Post-SSRI sexual dysfunction: a literature review. Sex Med Rev. 2018;6(1):29–34.PubMed
11.
Price J, Cole V, Goodwin GM. Emotional side-effects of selective serotonin reuptake inhibitors: qualitative study. Br J Psychiatry. 2009;195(3):211–7.PubMed
12.
Cartwright C, Gibson K, Read J, Cowan O, Dehar T. Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient Prefer Adherence. 2016;10:1401–7.PubMedPubMedCentral
13.
Coupland C, Dhiman P, Morriss R, Arthur A, Barton G, Hippisley-Cox J. Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ. 2011;343:d4551.PubMedPubMedCentral
14.
15.
Hengartner MP, Schulthess L, Sorensen A, Framer A. Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum. Ther Adv Psychopharmacol. 2020;10:2045125320980573.PubMedPubMedCentral
16.
Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: are guidelines evidence-based? Addict Behav. 2019;97:111–21.PubMed
17.
Cosci F, Chouinard G. Acute and persistent withdrawal syndromes following discontinuation of psychotropic medications. Psychother Psychosom. 2020;89(5):283–306.PubMed
18.
Horowitz MA, Taylor D. Distinguishing relapse from antidepressant withdrawal: clinical practice and antidepressant discontinuation studies. BJPsych Adv. 2022;28(5):297–311.
19.
White E, Read J, Julo S. The role of Facebook groups in the management and raising of awareness of antidepressant withdrawal: is social media filling the void left by health services? Ther Adv Psychopharmacol. 2021;11:2045125320981174.PubMedPubMedCentral
20.
21.
Cruickshank G, Macgillivray S, Bruce D, Mather A, Matthews K, Williams B. Cross-sectional survey of patients in receipt of long-term repeat prescriptions for antidepressant drugs in primary care. Ment Health Fam Med. 2008;5(2):105–9.PubMedPubMedCentral
22.
Guy A, Brown M, Lewis S, Horowitz M. The ‘patient voice’: patients who experience antidepressant withdrawal symptoms are often dismissed, or misdiagnosed with relapse, or a new medical condition. Ther Adv Psychopharmacol. 2020;10:2045125320967183.PubMedPubMedCentral
23.
Read J, Moncrieff J, Horowitz MA. Designing withdrawal support services for antidepressant users: patients’ views on existing services and what they really need. J Psychiatr Res. 2023;161:298–306.PubMed
24.
Maund E, Dewar-Haggart R, Williams S, Bowers H, Geraghty AWA, Leydon G, et al. Barriers and facilitators to discontinuing antidepressant use: a systematic review and thematic synthesis. J Affect Disord. 2019;245:38–62.PubMed
25.
Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. Lancet Psychiatry. 2019;6(6):538–46.PubMed
26.
Framer A. What I have learnt from helping thousands of people taper off antidepressants and other psychotropic medications. Ther Adv Psychopharmacol. 2021;11:2045125321991274.PubMedPubMedCentral
27.
Groot PC, van Os J. Successful use of tapering strips for hyperbolic reduction of antidepressant dose: a cohort study. Ther Adv Psychopharmacol. 2021;11:20451253211039330.PubMedPubMedCentral
28.
van Os J, Groot PC. Outcomes of hyperbolic tapering of antidepressants. Ther Adv Psychopharmacol. 2023;13:20451253231171520.PubMedPubMedCentral
29.
Meyer JH, Wilson AA, Sagrati S, Hussey D, Carella A, Potter WZ, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry. 2004;161(5):826–35.PubMed
30.
31.
32.
33.
Ogle NR, Akkerman SR. Guidance for the discontinuation or switching of antidepressant therapies in adults. J Pharm Pract. 2013;26(4):389–96.PubMed
34.
Wallis KA, Donald M, Moncrieff J. Antidepressant prescribing in general practice: a call to action. Aust J Gen Pract. 2021;50(12):954–6.PubMed
35.
Eveleigh R, Muskens E, Lucassen P, Verhaak P, Spijker J, van Weel C, et al. Withdrawal of unnecessary antidepressant medication: a randomised controlled trial in primary care. BJGP Open. 2018;1(4):17X101265.
36.
Curran GM, Bauer M, Mittman B, Pyne JM, Stetler C. Effectiveness-implementation hybrid designs: combining elements of clinical effectiveness and implementation research to enhance public health impact. Med Care. 2012;50(3):217–26.PubMedPubMedCentral
37.
Wallis KA, Andrews A, Henderson M. Swimming against the tide: primary care physicians’ views on deprescribing in everyday practice. Ann Fam Med. 2017;15(4):341–6.PubMedPubMedCentral
38.
Wallis KA, Tuckey R. Safer Prescribing and Care for the Elderly (SPACE): feasibility of audit and feedback plus practice mail-out to patients with high-risk prescribing. J Prim Health Care. 2017;9(2):145–52.PubMed
39.
Donald M, Partanen R, Sharman L, Lynch J, Dingle GA, Haslam C, et al. Long-term antidepressant use in general practice: a qualitative study of GPs’ views on discontinuation. Br J Gen Pract. 2021;71(708):E508–16.PubMedPubMedCentral
40.
Glasgow RE, Eakin EG, Fisher EB, Bacak SJ, Brownson RC. Physician advice and support for physical activity: results from a national survey. Am J Prev Med. 2001;21(3):189–96.PubMed
41.
Glasgow RE, Emont S, Miller DC. Assessing delivery of the five ‘As’ for patient-centered counseling. Health Promot Int. 2006;21(3):245–55.PubMed
42.
Ware JE, Kosinski M, Keller SD. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34(3):220–33.PubMed
43.
Hodgson K, Uher R, Crawford AA, Lewis G, O’Donovan MC, Keers R, et al. Genetic predictors of antidepressant side effects: a grouped candidate gene approach in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study. J Psychopharmacol. 2014;28(2):142–50.PubMed
44.
Uher R, Farmer A, Henigsberg N, Rietschel M, Mors O, Maier W, et al. Adverse reactions to antidepressants. Br J Psychiatry. 2009;195(3):202–10.PubMed
45.
Maheswaran H, Weich S, Powell J, Stewart-Brown S. Evaluating the responsiveness of the Warwick Edinburgh Mental Well-Being Scale (WEMWBS): group and individual level analysis. Health Qual Life Outcomes. 2012;10(1):156.PubMedPubMedCentral
46.
Moncrieff J, Read J, Horowitz M. Severity of antidepressant withdrawal effects versus symptoms of underlying conditions. 2023; (in preparation).
47.
48.
Orsillo SM, Theodore-Oklota C, Luterek JA, Plumb J. The development and psychometric evaluation of the emotional reactivity and numbing scale. J Nerv Ment Dis. 2007;195(10):830–6.PubMed
49.
Horne R, Weinman J, Hankins M. The beliefs about medicines questionnaire: the development and evaluation of a new method for assessing the cognitive representation of medication. Psychol Health. 1999;14(1):1–24.
50.
Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–13.PubMedPubMedCentral
51.
Gilbody S, Richards D, Barkham M. Diagnosing depression in primary care using self-completed instruments: UK validation of PHQ–9 and CORE–OM. Br J Gen Pract. 2007;57(541):650–2.PubMedPubMedCentral
52.
Spitzer RL, Kroenke K, Williams JBW, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–7.PubMed
53.
Kroenke K, Spitzer RL, Williams JBW, Monahan PO, Löwe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med. 2007;146(5):317–25.PubMed
54.
Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009;4(1):50.PubMedPubMedCentral
55.
Huijbers MJ, Wentink C, Simons E, Spijker J, Speckens A. Discontinuing antidepressant medication after mindfulness-based cognitive therapy: a mixed-methods study exploring predictors and outcomes of different discontinuation trajectories, and its facilitators and barriers. BMJ Open. 2020;10(11):e039053.PubMedPubMedCentral
Metadata
Title
RELEASE (REdressing Long-tErm Antidepressant uSE): protocol for a 3-arm pragmatic cluster randomised controlled trial effectiveness-implementation hybrid type-1 in general practice
Authors
Katharine A. Wallis
Maria Donald
Mark Horowitz
Joanna Moncrieff
Robert S. Ware
Joshua Byrnes
Karen Thrift
MaryAnne Cleetus
Idin Panahi
Nicholas Zwar
Mark Morgan
Chris Freeman
Ian Scott
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Trials / Issue 1/2023
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-023-07646-w

Other articles of this Issue 1/2023

Trials 1/2023 Go to the issue

Study protocol

Evaluating interventions to reduce behaviour associated with HCV reinfection in men who have sex with men: study protocol for a non-blinded, phase 2, randomised trial

Research

Implementation challenges and lessons learned from the STREAM clinical trial—a survey of trial sites

Study protocol

Investigation on the effect of antimicrobial photodynamic therapy as an adjunct for management of deep caries lesions—study protocol for a randomized, parallel groups, controlled clinical trial

Study protocol

Leukocyte- and platelet-rich fibrin in endoscopic endonasal skull base reconstruction: study protocol for a multicenter prospective, parallel-group, single-blinded randomized controlled non-inferiority trial

Study protocol

Potential cognitive and neural benefits of a computerised cognitive training programme based on Structure Learning in healthy adults: study protocol for a randomised controlled trial

Study protocol

A single-blind, parallel-group randomised trial of a Technology-assisted and remotely delivered Cognitive Behavioural Therapy intervention (Tech-CBT) versus usual care to reduce anxiety in people with mild cognitive impairment and dementia: study protocol for a randomised trial