Fornaro, 2018 The Emergence of loss of efficacy during Antidepressant Drug Treatment for Major Depressive Disorder: An Integrative Review of Evidence, Mechanisms, and Clinical Implications.

[Altostrata]

Pharmacol Res. 2018 Oct 29. pii: S1043-6618(18)31201-5. doi: 10.1016/j.phrs.2018.10.025. [Epub ahead of print]

The Emergence of loss of efficacy during Antidepressant Drug Treatment for Major Depressive Disorder: An Integrative Review of Evidence, Mechanisms, and Clinical Implications.

Fornaro M1, Anastasia A2, Novello S3, Fusco A4, Pariano R5, De Berardis D6, Solmi M7, Veronese N8, Stubbs B9, Vieta E10, Berk M11, de Bartolomeis A12, Carvalho AF13.

 

Abstract at https://www.ncbi.nlm.nih.gov/pubmed/30385364

 

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.

[Linus]

Lol, loss of efficacy, there is no efficacy to begin with.

 

Several of the researchers involved with the study have financial ties to manufacturers of antidepressants.

 

The following is the disclosure statement for the authors of this paper:

 

EV has received grants and served as a consultant, advisor, or CME speaker for the following entities: AB-Biotics, Allergan, AstraZeneca, Bristol-Myers-Squibb, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, SanofiAventis, Servier, Shire, Sunovion, Takeda, Telefonica, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (Centro de Investigación Biomédica en Red de Salud Mental), the Seventh European Framework Programme (European Network of Bipolar Research Expert Centres), and the Stanley Medical Research Institute. MB is supported by an NHMRC Senior Principal Research Fellowship (APP1059660) and has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Meat and Livestock Board, Astra Zeneca, Woolworths, Avant and the Harry Windsor Foundation, book royalties from Oxford University Press, Cambridge University Press, Springer Nature and Allen and Unwin, has been a speaker for Astra Zeneca, Lundbeck, Merck and Servier and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Grunbiotics, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka and Servier. The other authors report no conflicts of interest. AdB has received research support from Janssen, Lundbeck, and Otsuka and lecture honoraria for unrestricted CME talks from Chiesi, Lundbeck, Roche, Sunovion, and Takeda; he has served on advisory boards for Eli Lilly, Jansen, Lundbeck, Otsuka, Roche, and Takeda.