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Antidepressant-induced jitteriness/anxiety syndrome: systematic review

Published online by Cambridge University Press:  02 January 2018

Lindsey I. Sinclair
Psychopharmacology Unit, University of Bristol, UK
David M. Christmas
Psychopharmacology Unit, University of Bristol, UK
Sean D. Hood
School of Psychiatry & Clinical Neurosciences (M521), The University of Western Australia, Perth, Australia
John P. Potokar
Psychopharmacology Unit, University of Bristol, UK
Andrea Robertson
Edinburgh (NHS) Community Health Partnership, Edinburgh, UK
Andrew Isaac
Warwickshire (NHS) Primary Care Trust, Warwick, UK
Shrikant Srivastava
Psychopharmacology Unit, University of Bristol, UK
David J. Nutt
Psychopharmacology Unit, University of Bristol, UK
Simon J. C. Davies*
Psychopharmacology Unit, University of Bristol, UK
Simon Davies, Psychopharmacology Unit, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK. Email:
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Early worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking.


To review systematically all evidence relating to jitteriness/ anxiety syndrome to identify: constituent symptoms; medications implicated; disorders in which it was reported; incidence; time course; management strategies; relationship of this syndrome to therapeutic response; distinction between syndrome and akathisia; relationship between syndrome and suicide; and genetic predispositions.


A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome.


Of 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome.


Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.

Review Article
Copyright © Royal College of Psychiatrists, 2009 


Declaration of interest

There are no direct conflicts of interest relating to any of the authors and the contents of this work. This study was not commissioned, funded or sponsored by any pharmaceutical company or other financial enterprise. Over the past 20 years D.J.N. and his research group (which during the period in which the review was designed and conducted has included S.J.C.D., S.D.H, D.M.C, S.S. A.R. and L.I.S) have received funds (research grants, speakers fees or consultancy payments) from every major pharmaceutical company with an interest in the psychiatric field. D.J.N. has also received legal fees from companies, medical defence organisations and the British Legal Aid board in relation to court cases regarding the effects of psychotropic drugs. He holds approximately 300 GlaxoSmithKline shares.


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