The failure of anxiolytic therapies in early clinical trials: What needs to be done

Adam Michael Stewart, Michael Nguyen, Manoj K. Poudel, Jason E. Warnick, David J. Echevarria, Elliott A. Beaton, Cai Song, Allan V. Kalueff*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)


Introduction: Anxiety spectrum disorders (ASDs) are highly prevalent psychiatric illnesses that affect millions of people worldwide. Strongly associated with stress, common ASDs include generalized anxiety disorder, panic, social anxiety, phobias and drug-abuse-related anxiety. In addition to ASDs, several other prevalent psychiatric illnesses represent trauma/stressor-related disorders, such as post-traumatic stress disorder and acute stress disorder. Anxiolytic drugs, commonly prescribed to treat ASDs and trauma/stressor-related disorders, form a highly heterogenous group, modulating multiple neurotransmitters and physiological mechanisms. However, overt individual differences in efficacy and the potential for serious side-effects (including addiction and drug interaction) indicate a need for further drug development. Yet, over the past 50 years, there has been relatively little progress in the development of novel anxiolytic medications, especially when promising candidate drugs often fail in early clinical trials.Areas covered: Herein, the authors present recommendations of the Task Force on Anxiolytic Drugs of the International Stress and Behavior Society on how to improve anxiolytic drug discovery. These recommendations cover a wide spectrum of aspects, ranging from methodological improvements to conceptual insights and innovation.Expert opinion: In order to improve the success of anxiolytic drugs in early clinical trials, the goals of preclinical trials may need to be adjusted from a clinical perspective and better synchronized with those of clinical studies. Indeed, it is important to realize that the strategic goals and approaches must be similar if we want to have a smoother transition between phases.

Original languageEnglish
Pages (from-to)543-556
Number of pages14
JournalExpert Opinion on Investigational Drugs
Issue number4
Publication statusPublished - 1 Apr 2015
Externally publishedYes


  • Anxiolytic drug
  • Clinical trial
  • Experimental model
  • Model organism
  • Preclinical study


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