title: Antidepressant-induced jitteriness/anxiety syndrome: systematic review.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Psychopharmacology Unit, University of Bristol, Dorothy Hodgkin Building, Bristol BS1 3NY, UK.
authors.forename: Lindsey I
authors.initials: LI
authors.lastname: Sinclair
authors.forename: David M
authors.initials: DM
authors.lastname: Christmas
authors.forename: Sean D
authors.initials: SD
authors.lastname: Hood
authors.forename: John P
authors.initials: JP
authors.lastname: Potokar
authors.forename: Andrea
authors.initials: A
authors.lastname: Robertson
authors.forename: Andrew
authors.initials: A
authors.lastname: Isaac
authors.forename: Shrikant
authors.initials: S
authors.lastname: Srivastava
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: Simon J C
authors.initials: SJ
authors.lastname: Davies
mesh_terms: D017109:Akathisia, Drug-Induced; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced*; D001008:Anxiety Disorders / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease; D006801:Humans; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013405:Suicide; D013577:Syndrome; D013997:Time Factors; D016312:Treatment Refusal
chemical_list: D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors