title: Correlates of therapeutic response in panic disorder presenting with palpitations: heart rate variability, sleep, and placebo effect.
abstract: OBJECTIVE
  To examine the correlates of therapeutic response of patients with panic disorder presenting with palpitations, we hypothesized that therapeutic response would correlate with heart rate variability (HRV) and sleep measures.
  
  
  METHODS
  After a 1-week placebo washout, 27 patients free of structural heart disease and not on cardioactive drugs were randomized in a double-blinded fashion to 4 weeks of treatment with clonazepam (a known antipanic agent) or placebo. We performed standard sleep measures and recorded HRV from 24-hour Holter acquisitions at baseline and end of study. We defined response to therapy as a 50% improvement in the Hamilton Anxiety Rating Scale (HARS) score, confirmed by questionnaires and reaction to sodium lactate infusion.
  
  
  RESULTS
  There were 12 responders and 15 nonresponders. Normalization of sleep pattern (including less stage 1 and rapid eye movement [REM] sleep) was observed in both drug and placebo responders (P = 0.011 and P = 0.05, respectively) and in placebo responders alone, compared with nonresponders (P = 0.006 and P = 0.013, respectively). Placebo responders were more likely to show less depression, but even after we controlled for depression, main sleep effects remained. None of the HRV measures correlated with response, but compared with placebo, clonazepam led to a decrease in all the time and frequency domain measures of HRV (all P < 0.05).
  
  
  CONCLUSIONS
  Central mechanisms are related to the therapeutic response of patients with panic disorder presenting with palpitations, but this does not directly correlate with HRV. Larger and longer studies may allow objective explanations of placebo response in panic disorder.
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario. brian.baker@utoronto.ca
authors.forename: Brian
authors.initials: B
authors.lastname: Baker
authors.forename: Yaariv
authors.initials: Y
authors.lastname: Khaykin
authors.forename: Gerald
authors.initials: G
authors.lastname: Devins
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
authors.forename: Colin
authors.initials: C
authors.lastname: Shapiro
authors.forename: David
authors.initials: D
authors.lastname: Newman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000209:etiology*; D002998:Clonazepam / Q000627:therapeutic use*; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000188:drug therapy* / Q000523:psychology*; D015990:Placebo Effect; D012720:Severity of Illness Index; D012890:Sleep; D011795:Surveys and Questionnaires
chemical_list: D000927:Anticonvulsants; D002998:Clonazepam