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The emergence of loss of efficacy during antidepressant drug treatment for major depressive disorder: An integrative review of evidence, mechanisms, and clinical implications

Version 2 2024-06-03, 19:29
Version 1 2018-11-27, 10:28
journal contribution
posted on 2024-06-03, 19:29 authored by M Fornaro, A Anastasia, S Novello, A Fusco, R Pariano, D De Berardis, M Solmi, N Veronese, B Stubbs, E Vieta, Michael BerkMichael Berk, A de Bartolomeis, AF Carvalho
The re-emergence (i.e. 'breakthrough') of depressive symptoms despite maintenance treatment of depression with antidepressant drugs is a complex clinical phenomenon referred to as tolerance. Herein we critically appraise evidence from both pre-clinical and clinical studies, focusing on putative mechanisms as well as clinical correlates and implications of the emergence tolerance during antidepressant treatment for major depressive disorder (MDD). It is firstly unclear to what extent this phenotype reflects a pharmacological effect of an antidepressant, is driven by non-adherence, is a marker of latent bipolarity or another comorbidity, a marker of neuroprogression of the underlying disorder or the intrusion of the impact of psychosocial variables into the clinical course. The operational definitions of tolerance and its related phenomena have also been largely inconsistent. Several protective clinical indicators have been proposed, including a rapid-cycling course and comorbid chronic anxiety, whilst poor treatment adherence, proneness to emotional blunting and sub-threshold bipolarity have been identified as possible correlates of tolerance to antidepressant treatment in MDD. Putative neurobiological underpinnings include adaptations in the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic system. Due to the clinical and diagnostic challenges imposed by the emergence of tolerance to antidepressants, there is an urgent need for upcoming international guidelines to reach a consensus on operational definitions for this complex clinical phenomenon, thus enabling a more precise appreciation of the incidence and correlates of tolerance to antidepressants. Taken together, the present review underscores the need to cautiously weight benefits and risks prior to considering long-term antidepressant treatment for patients with MDD as tolerance may emerge in a subset of patients.

History

Journal

Pharmacological Research

Volume

139

Pagination

494-502

Location

Netherlands

ISSN

1043-6618

eISSN

1096-1186

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2018, Elsevier Ltd.

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD