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Antidepressant Treatment in Anxiety Disorders

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Behavioral Neurobiology of Anxiety and Its Treatment

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 2))

Abstract

Antidepressant drug treatment is the clinical standard of care for all types of anxiety disorders. Broad efficacy of selective serotonin reuptake inhibitors suggests the importance of enhanced serotonergic function of the anxiolytic properties of current antidepressants. However, analysis of the preclinical evidence indicates that most conventional “anxiolytic” drug tests are not sensitive to antidepressants. Such dissociation is not surprising because of the traditional approach to validation of preclinical tests that is to a large extent based on establishing face validity as well as sensitivity to benzodiazepine anxiolytics. The present review argues for extending the cognitive model of antidepressant drug action to cover their anxiolytic properties as well. Such an approach is based on ambiguity or uncertainty in a broad sense as the hallmark of human stress that has different expressions ready for experimental modeling. These possibilities include schedule-induced behaviors that are directly based on intermittent reinforcement, conditioning to ambiguous stimuli, social stress where agonistic confrontations are possible but not predictable or controlled by the subject, and an even larger class of behaviors that are critically dependent on the inhibition of the prepotent responses in exchange for the ambiguous possibility of a later gain in reinforcement. Interestingly, in all these cases, antidepressant drug treatment is clearly effective in preclinical laboratory settings. One of the cognitive functions that appears to be affected by antidepressant drugs is inhibitory control. Inhibition of prepotent responding has beneficial effects in the “uncertainty” stress situations discussed above and therefore it is this cognitive function that may be critical for anxiolytic effects of antidepressants and novel anxiolytic drug development.

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Notes

  1. 1.

    First clinical reports suggested efficacy in the treatment of GAD but this evidence needs to be further extended by additional studies, with active comparisons as well as over longer periods of time (Stein et al. 2008).

  2. 2.

    First clinical studies indicated lack of clinical efficacy of CRF1 antagonists in the treatment of GAD (Coric et al. 2008; see also Steckler*** 2009). However, it may be too early to interpret this evidence because, even successful drug classes like SSRIs took several clinical trials to firmly establish their clinical usefulness.

  3. 3.

    It is of note that subchronic treatment with SSRIs like fluoxetine may attenuate stress-induced behaviors but has little or no effects on stress-induced increases in ACTH and corticosterone levels (Zhang et al. 2000).

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  1. Neuroscience Research, GPRD, Abbott, 21 08 05, 67008, Ludwigshafen, Germany

    Anton Y. Bespalov, Marcel M. van Gaalen & Gerhard Gross

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  1. Anton Y. Bespalov
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  2. Marcel M. van Gaalen
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Correspondence to Anton Y. Bespalov .

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  1. Dept. Psychiatry, University of California, San Diego, Gilman Drive 9500, La Jolla, 92093-0985, USA

    Murray B. Stein

  2. Research & Development, CNS - Affective Spectrum, Johnson & Johnson Pharmaceutical, Turnhoutseweg 30, Beerse, 2340, Belgium

    Thomas Steckler

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Bespalov, A.Y., van Gaalen, M.M., Gross, G. (2009). Antidepressant Treatment in Anxiety Disorders. In: Stein, M., Steckler, T. (eds) Behavioral Neurobiology of Anxiety and Its Treatment. Current Topics in Behavioral Neurosciences, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2009_3

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