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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
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 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
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