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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions
World Psychiatry, Volume 22, No. 3, Year 2023
Notification
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Description
Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population. © 2023 World Psychiatric Association.
Authors & Co-Authors
Mcintyre, Roger S.
Canada, Toronto
University of Toronto
Baune, Bernhard T.
Germany, Munster
University of Münster
Australia, Melbourne
University of Melbourne
Berk, Michael
Australia, Melbourne
University of Melbourne
Australia, Geelong
Deakin University
Demyttenaere, Koen
Belgium, Leuven
Ku Leuven
Goldberg, Joseph F.
United States, New York
Icahn School of Medicine at Mount Sinai
Gorwood, Philip A.P.M.
France, Paris
Centre Hospitalier Sainte-anne
Ho, Roger C.M.
Singapore, Singapore City
National University of Singapore
Kasper, Siegfried F.
Austria, Vienna
Medizinische Universität Wien
Kennedy, Sidney H.
Canada, Toronto
University of Toronto
Ly-Uson, Josefina T.
Philippines, Manila
University of the Philippines College of Medicine
Nierenberg, Andrew Alan
United States, Boston
Massachusetts General Hospital
Rosenblat, Joshua D.
Canada, Toronto
University of Toronto
Sanacora, Gerard S.
United States, New Haven
Yale University
Trivedi, Madhukar H.
United States, Chicago
University of Illinois at Chicago
Vieta, Eduard
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
Young, Allan H.
United Kingdom, London
King's College London
Maj, Mario
Italy, Naples
Università Degli Studi Della Campania Luigi Vanvitelli
Statistics
Citations: 43
Authors: 17
Affiliations: 22
Identifiers
Doi:
10.1002/wps.21120
ISSN:
17238617
Research Areas
Food Security
Genetics And Genomics
Mental Health
Substance Abuse
Study Design
Randomised Control Trial
Cross Sectional Study