Understanding antidepressant discontinuation syndrome (ADS) through preclinical experimental models

Konstantin N Zabegalov; Tatiana O Kolesnikova; Sergey L Khatsko; Andrey D Volgin; Oleg A Yakovlev; Tamara G Amstislavskaya; Polina A Alekseeva; Darya A Meshalkina; Ashton J Friend; Wandong Bao; Konstantin A Demin; Raul R Gainetdinov; Allan V Kalueff

doi:10.1016/j.ejphar.2018.04.003

Understanding antidepressant discontinuation syndrome (ADS) through preclinical experimental models

Eur J Pharmacol. 2018 Jun 15:829:129-140. doi: 10.1016/j.ejphar.2018.04.003. Epub 2018 Apr 5.

Affiliations

¹ Ural Federal University, Ekaterinburg, Russia.
² Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.
³ Laboratory of Translational Biopsychiatry, Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia; Department of Neuroscience, Novosibirsk State University, Novosibirsk, Russia.
⁴ Institute of Experimental Medicine, Almazov National Medical Research Centre, St. Petersburg, Russia.
⁵ Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia; Institute of Experimental Medicine, Almazov National Medical Research Centre, St. Petersburg, Russia.
⁶ The International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell, LA, USA; Tulane University School of Science and Engineering, New Orleans, USA.
⁷ School of Pharmacy, Southwest University, Chongqing, China.
⁸ School of Pharmacy, Southwest University, Chongqing, China; The International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell, LA, USA; Chemical Institute, Ural Federal University, Ekaterinburg, Russia; ZENEREI Research Center, Slidell, LA, USA; Laboratory of Biological Psychiatry, ITBM, St. Petersburg State University, St. Petersburg, Russia; Institute of Experimental Medicine, Almazov National Medical Research Centre, St. Petersburg, Russia; Granov Russian National Center for Radiology and Surgical Technologies, Pesochny, Russia; Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia. Electronic address: avkalueff@gmail.com.

PMID: 29627310
DOI: 10.1016/j.ejphar.2018.04.003

Abstract

Antidepressant drugs are currently one of the most prescribed medications. In addition to treatment resistance and side effects of antidepressants, their clinical use is further complicated by antidepressant discontinuation syndrome (ADS). ADS is a common problem in patients following the interruption, dose reduction, or discontinuation of antidepressant drugs. Clinically, ADS resembles a classical drug withdrawal syndrome, albeit differing from it because antidepressants generally do not induce addiction. The growing clinical importance and prevalence of ADS necessitate novel experimental (animal) models of this disorder. Currently available preclinical models of ADS are mainly rodent-based, and study mostly serotonergic antidepressants and their combinations. Here, we systematically assess clinical ADS symptoms and discuss current trends and challenges in the field of experimental (animal) models of ADS. We also outline basic mechanisms underlying ADS pathobiology, evaluate its genetic, pharmacological and environmental determinants, and emphasize how using animal models may help generate important translational insights into human ADS condition, its prevention and therapy.

Keywords: Animal models; Antidepressants; Depression; Discontinuation syndrome; Side effects.

Publication types

Review

MeSH terms

Animals
Antidepressive Agents / adverse effects*
Disease Models, Animal
Humans
Substance Withdrawal Syndrome / etiology*

Substances

Antidepressive Agents