Archival Report| Volume 70, ISSUE 10, P985-991, November 15, 2011

Do Unexpected Panic Attacks Occur Spontaneously?


      Spontaneous or unexpected panic attacks, per definition, occur “out of the blue,” in the absence of cues or triggers. Accordingly, physiological arousal or instability should occur at the onset of, or during, the attack, but not preceding it. To test this hypothesis, we examined if points of significant autonomic changes preceded the onset of spontaneous panic attacks.


      Forty-three panic disorder patients underwent repeated 24-hour ambulatory monitoring. Thirteen natural panic attacks were recorded during 1960 hours of monitoring. Minute-by-minute epochs beginning 60 minutes before and continuing to 10 minutes after the onset of individual attacks were examined for respiration, heart rate, and skin conductance level. Measures were controlled for physical activity and vocalization and compared with time matched control periods within the same person.


      Significant patterns of instability across a number of autonomic and respiratory variables were detected as early as 47 minutes before panic onset. The final minutes before onset were dominated by respiratory changes, with significant decreases in tidal volume followed by abrupt carbon dioxide partial pressure increases. Panic attack onset was characterized by heart rate and tidal volume increases and a drop in carbon dioxide partial pressure. Symptom report was consistent with these changes. Skin conductance levels were generally elevated in the hour before, and during, the attacks. Changes in the matched control periods were largely absent.


      Significant autonomic irregularities preceded the onset of attacks that were reported as abrupt and unexpected. The findings invite reconsideration of the current diagnostic distinction between uncued and cued panic attacks.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Craske M.G.
        • Kircanski K.
        • Epstein A.
        • Wittchen H.U.
        • Pine D.S.
        • Lewis-Fernandez R.
        • et al.
        Panic disorder: A review of DSM-IV panic disorder and proposals for DSM-V.
        Depress Anxiety. 2010; 27: 93-112
        • Baillie A.J.
        • Rapee R.M.
        Panic attacks as risk markers for mental disorders.
        Soc Psychiatry Psychiatr Epidemiol. 2005; 40: 240-244
        • Goodwin R.D.
        • Hamilton S.P.
        Panic attack as a marker of core psychopathological processes.
        Psychopathology. 2001; 34: 278-288
        • Reed V.
        • Wittchen H.U.
        DSM-IV panic attacks and panic disorder in a community sample of adolescents and young adults: How specific are panic attacks?.
        J Psychiatr Res. 1998; 32: 335-345
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders.
        4th ed. American Psychiatric Association, Washington, DC1994
        • Klein D.F.
        • Klein H.M.
        The substantive effect of variations in panic measurement and agoraphobia definition.
        J Anxiety Disord. 1989; 3: 45-56
        • Freud S.
        Obsessions and phobias; their psychical mechanisms and their aetiology.
        in: Riviere Joan Collected Papers. vol. 1. Hogarth Press, London1924 ([Original work published in 1895])
        • Wilkinson D.J.C.
        • Thompson J.M.
        • Lambert G.W.
        • Jennings G.L.
        • Schwarz R.G.
        • Jefferys D.
        • et al.
        Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks.
        Arch Gen Psychiatry. 1998; 55: 511-520
        • Freedman R.R.
        • Ianni P.
        • Ettedgui E.
        • Puthezhath N.
        Ambulatory monitoring of panic disorder.
        Arch Gen Psychiatry. 1985; 42: 244-248
        • Cohen A.S.
        • Barlow D.H.
        • Blanchard E.B.
        Psychophysiology of relaxation-associated panic attacks.
        J AbnormPsychol. 1985; 94: 96-101
        • Lader M.
        • Mathews A.
        Physiological changes during spontaneous panic attacks.
        J Psychosom Res. 1970; 14: 377-382
        • Goetz R.R.
        • Klein D.F.
        • Gully R.
        • Kahn J.
        • Liebowitz M.R.
        • Fyer A.J.
        • Gorman J.M.
        Panic attacks during placebo procedures in the laboratory: Physiology and symptomatology.
        Arch Gen Psychiatry. 1993; 50: 280-285
        • Taylor C.B.
        • Telch M.J.
        • Havvik D.
        Ambulatory heart rate changes during panic attacks.
        J Psychiatr Res. 1982–; 17: 261-266
        • Taylor C.B.
        • Sheikh M.D.
        • Agras W.S.
        • Roth W.T.
        • Margraf J.
        • Ehlers A.
        • et al.
        Ambulatory heart rate changes in patients with panic attacks.
        Am J Psychiatry. 1986; 143: 478-482
        • Gaffney F.A.
        • Fenton B.J.
        • Lane L.D.
        • Lake C.R.
        Hemodynamic, ventilatory, and biochemical responses of panic patients and normal controls with sodium lactate infusion and spontaneous panic attacks.
        Arch Gen Psychiatry. 1988; 45: 53-60
        • Cameron O.G.
        • Lee M.A.
        • Curtis G.C.
        • McCann D.S.
        Endocrine and physiological changes during ‘spontaneous’ panic attacks.
        Psychoneuroendocrinology. 1987; 12: 321-331
        • Bystritsky A.
        • Craske M.
        • Maidenberg E.
        • Vapnik T.
        • Shapiro D.
        Ambulatory monitoring of panic patients during regular activity: A preliminary report.
        Biol Psychiatry. 1995; 38: 684-689
        • Klein D.F.
        False suffocation alarms, spontaneous panics, and related conditions.
        Arch Gen Psychiatry. 1993; 50: 306-317
        • Ley R.A.
        Blood, breath and fears: A hyperventilation theory of panic attacks and agoraphobia.
        Clin Psychol Rev. 1985; 5: 271-285
        • Hibbert G.
        • Pilsbury D.
        Hyperventilation in panic attacks: Ambulant monitoring of transcutaneous carbon dioxide.
        Br J Psychiatry. 1988; 153: 76-80
        • Garssen B.
        • Buikhuise M.
        • van Dyck R.
        Hyperventilation and panic attacks.
        Am J Psychiatry. 1996; 153: 513-518
        • Martinez J.M.
        • Papp L.A.
        • Coplan J.D.
        • Anderson D.E.
        • Mueller C.M.
        • Klein D.F.
        • Gorman J.M.
        Ambulatory monitoring of respiration in anxiety.
        Anxiety. 1996; 2: 296-302
        • Salkovskis P.M.
        • Warwick H.M.
        • Clark D.M.
        • Wessels D.J.
        A demonstration of acute hyperventilation during naturally occurring panic attacks.
        Behav Res Ther. 1986; 24: 91-94
        • Meuret A.E.
        • Wilhelm F.H.
        • Ritz T.
        • Roth W.T.
        Feedback of end-tidal pCO2 as a therapeutic approach for panic disorder.
        J Psychiatr Res. 2008; 42: 560-568
        • First M.B.
        • Spitzer R.L.
        • Gibbon M.
        • Williams J.B.W.
        Structured Clinical Interview for DSM–IV Axis I Disorders-Patient Edition (SCID-IP, Version 2.0). Biometrics Research Department, New York State Psychiatric Institute, New York1994
        • Shear M.K.
        • Brown T.A.
        • Barlow D.H.
        • Money R.
        • Sholomsskas D.E.
        • Woods S.W.
        • et al.
        Multicenter collaborative Panic Disorder Severity Scale.
        Am J Psychiatry. 1997; 154: 1571-1575
        • Chadha T.S.
        • Watson H.
        • Birch S.
        • Jenouri G.A.
        • Schneider A.W.
        • Cohn M.A.
        • Sackner M.A.
        Validation of respiratory inductive plethysmography using different calibration procedures.
        Am Rev Respir Dis. 1982; 125: 644-649
        • Wilhelm F.H.
        • Grossman P.
        Emotions beyond the laboratory: Theoretical fundaments, study design, and analytic strategies for advanced ambulatory assessment.
        Biol Psychol. 2010; 84: 552-569
        • Conrad A.
        • Isaac L.
        • Roth W.T.
        The psychophysiology of generalized anxiety disorder: 1.
        Psychophysiology. 2008; 45: 366-376
        • Lindquist M.A.
        • Waugh C.
        • Wager T.D.
        Modeling state-related fMRI activity using change-point theory.
        Neuroimage. 2007; 35: 1125-1141
        • Rosenfield D.
        • Zhou E.
        • Wilhelm F.H.
        • Conrad A.
        • Roth W.T.
        • Meuret A.E.
        Change point analysis for longitudinal physiological data: Detection of cardio-respiratory changes preceding panic attacks.
        Biol Psychol. 2010; 84: 112-120
        • Barlow D.H.
        • Brown T.A.
        • Craske M.G.
        Definitions of panic attacks and panic disorder in the DSM-IV: Implications for research.
        J Abnorm Psychol. 1994; 103: 553-564
        • Sinha S.
        • Papp L.A.
        • Gorman J.M.
        How study of respiratory physiology aided our understanding of abnormal brain function in panic disorder.
        J Affect Disord. 2000; 61: 191-200
        • Street L.L.
        • Craske M.G.
        • Barlow D.H.
        Sensations, cognitions and the perception of cues associated with expected and unexpected panic attacks.
        Behav Res Ther. 1989; 27: 189-198
        • Kenardy J.
        • Taylor C.B.
        Expected versus unexpected panic attacks: A naturalistic prospective study.
        J Anxiety Disord. 1999; 13: 435-445