Skip to main content Accessibility help
  • Print publication year: 2008
  • Online publication date: May 2010

32 - Panic disorder

from Part III - Specific treatments


Editor's note

Panic disorder is a relatively new diagnosis that did not exist formally before 1980, when it was first introduced into DSM-III. Its introduction divided the primary anxiety disorders into panic and generalized anxiety disorder. The assets of the diagnosis are also its handicaps. The experience of a panic attack is so profound that it cannot but be remembered starkly and clearly, and so the definition of a panic attack is remarkably easy. However, most psychiatrists never see someone having a severe panic attack, and so the reporting of symptoms is for the most part retrospective and possibly distorted by the experience. This has led to difficulty in defining panic disorder, and the official classifications of DSM and ICD differ to some extent in that ICD-10 maintains that the panic attacks in panic disorder ‘are not consistently associated with a specific symptom or object’ (as when they are symptoms forming part of a phobic disorder), whereas in DSM IV, the exclusion clause that ‘they are not better accounted for by another mental disorder’ is much more open to interpretation. Panic attacks are said to be ‘uncued’ (i.e. they come ‘out of the blue’), but increasingly, as this chapter illustrates, they are often associated with a variety of cues. It is a condition which is not so much treated, but prevented, as the successful treatments prevent the disorder (i.e. stop) the panic attacks rather than treat them.

American Psychiatric Association (APA) (1994). DSM-IV Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association.
American Psychiatric Association (APA) (1998). Practice guideline for the treatment of patients with panic disorder. Work Group on Panic Disorder. American Psychiatric Association. American Journal of Psychiatry, 155(5 Suppl), 1–34.
Arntz, A. & Hout, M. (1996). Psychological treatments of panic disorder without agoraphobia: cognitive therapy versus applied relaxation. Behaviour Research Therapy, 34(2), 113–21.
Aschenbrand, S. G., Kendall, P. C., Webb, A., Safford, S. M. & Flannery-Schroeder, E. (2003). Is childhood separation anxiety disorder a predictor of adult panic disorder and agoraphobia? A seven-year longitudinal study. Journal of the American Academy of Child and Adolescent Psychiatry, 42(12), 1478–85.
Bakker, A., Balkom, A. J. & Spinhoven, P. (2002). SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis. Acta Psychiatrica Scandinavica, 106(3), 163–7.
Barlow, D. H. (1988). Anxiety and its Disorders: The Nature and Treatment of Anxiety and Panic. New York, NY: Guilford Press.
Barlow, D. H. (2002). Anxiety and its Disorders: The Nature and Treatment of Anxiety and Panic. New York, NY: Guilford Press.
Barlow, D. H., Gorman, J. M., Shear, M. K. & Woods, S. W. (2000). Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: a randomized controlled trial. Journal of the American Medical Association, 283(19), 2529–36.
Barlow, J. H., Ellard, D. R., Hainsworth, J. M., Jones, F. R. & Fisher, A. (2005). A review of self-management interventions for panic disorders, phobias and obsessive-compulsive disorders. Acta Psychiatrica Scandinavica, 111(4), 272–85.
Barrett, P. M. L., Lock, S. & Farrell, J. (2005). Developmental differences in universal preventive intervention for child anxiety. Clinical Child Psychology and Psychiatry, 10(4), 539–55.
Bebbington, P. E., Brugha, T. S., Meltzer, al. (2000). Neurotic disorders and the receipt of psychiatric treatment. Psychological Medicine, 30(6), 1369–76.
Biederman, J., Faraone, S. V., Marrs, al. (1997). Panic disorder and agoraphobia in consecutively referred children and adolescents. Journal of the American Academy of Child and Adolescent Psychiatry, 36(2), 214–23.
Biederman, J., Petty, C., Faraone, S. al. (2005). Parental predictors of pediatric panic disorder/agoraphobia: a controlled study in high-risk offspring. Depression and Anxiety, 22(3), 114–20.
Bienvenu, O. J., Onyike, C. U., Stein, M. al. (2006). Agoraphobia in general population adults: incidence and longitudinal relationships with panic, with clinical reappraisal. British Journal of Psychiatry, 188, 432–8.
Block, R. I., Ghoneim, M. M., Fowles, D. C., Kumar, V. & Pathak, D. (1987). Effects of a subanesthetic concentration of nitrous oxide on establishment, elicitation, and semantic and phonemic generalization of classically conditioned skin conductance responses. Pharmacological and Biochemical Behaviour, 28(1), 7–14.
Bouton, M. E., Mineka, S. & Barlow, D. H. (2001). A modern learning theory perspective on the etiology of panic disorder. Psychological Review, 108(1), 4–32.
Bower, P. & Gilbody, S. (2005). Stepped care in psychological therapies: access, effectiveness and efficiency. Narrative literature review. British Journal of Psychiatry, 186, 11–17.
Boyer, W. (1995). Serotonin uptake inhibitors are superior to imipramine and alprazolam in alleviating panic attacks: a meta-analysis. International Clinical Psychopharmacology, 10(1), 45–9.
Bradwejn, J., Ahokas, A., Stein, D. J., Salinas, E., Emilien, G. & Whitaker, T. (2005). Venlafaxine extended-release capsules in panic disorder: flexible-dose, double-blind, placebo-controlled study. British Journal of Psychiatry, 187, 352–9.
Bruce, S. E., Vasile, R. G., Goisman, R. al. (2003). Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia? American Journal of Psychiatry, 160(8), 1432–8.
Bruce, S. E., Yonkers, K. A., Otto, M. al. (2005). Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. American Journal of Psychiatry, 162(6), 1179–87.
Carlbring, P., Nilsson-Ihrfelt, E., Waara, al. (2005). Treatment of panic disorder: live therapy vs. self-help via the Internet. Behavior Research Therapy, 43(10), 1321–33.
Charney, D. S., Woods, S. W., Goodman, W. al. (1986). Drug treatment of panic disorder: the comparative efficacy of imipramine, alprazolam, and trazodone. Journal of Clinical Psychiatry, 47(12), 580–6.
Clark, D. M. (1986). A cognitive approach to panic. Behaviour Research Therapy, 24(4), 461–70.
Clark, D. M., Salkovskis, P. M., Gelder, M. et al. (1988). Test of a cognitive theory of panic. In Panic and Phobias II: Treatments and Variables Affecting Course and Outcome, ed. Hand, I. & Wittchen, H. V., pp. 71–90. Berlin: Springer-Verlag.
Clark, D. M., Salkovskis, P. M., Hackmann, A., Wells, A., Ludgate, J. & Gelder, M. (1999). Brief cognitive therapy for panic disorder: a randomised controlled trial. Journal of Consulting and Clinical Psychology, 67, 583–9.
Craske, M. G. (1999). Anxiety Disorders: Psychological Approaches to Theory and Treatment. Boulder, CO: Westview Press.
Craske, M. G., Lang, A. J., Rowe, al. (2002). Presleep attributions about arousal during sleep: nocturnal panic. Journal of Abnormal Psychology, 111(1), 53–62.
Craske, M. G., Edlund, M. J., Sullivan, al. (2005). Perceived unmet need for mental health treatment and barriers to care among patients with panic disorder. Psychiatric Services, 56(8), 988–94.
Beurs, E., Lange, A., Dyck, R. & Koele, P. (1995). Respiratory training prior to exposure in vivo in the treatment of panic disorder with agoraphobia: efficacy and predictors of outcome. Australian and N Z Journal of Psychiatry, 29(1), 104–13.
Gardenswarz, C. & Craske, M. (2001). Prevention of panic. Behavior Therapy, 32, 725–38.
Garssen, C. & Dyck, R. (1992). Breathing retraining: a rational placebo? Clinical Psychology Review, 12(2), 141–53.
Goddard, A. W., Brouette, T., Almai, A., Jetty, P., Woods, S. W. & Charney, D. (2001). Early coadministration of clonazepam with sertraline for panic disorder. Archives of General Psychiatry, 58(7), 681–6.
Goddard, A. W., Mason, G. F., Almai, al. (2001). Reductions in occipital cortex GABA levels in panic disorder detected with 1h-magnetic resonance spectroscopy. Archives in General Psychiatry, 58(6), 556–61.
Goddard, A. W., Mason, G. F., Appel, al. (2004). Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder. American Journal of Psychiatry, 161(12), 2186–93.
Goisman, R. M., Goldenberg, I., Vasile, R. G. & Keller, M. B. (1995). Comorbidity of anxiety disorders in a multicenter anxiety study. Comparative Psychiatry, 36(4), 303–11.
Goodwin, R. D. & Hoven, C. W. (2002). Bipolar-panic comorbidity in the general population: prevalence and associated morbidity. Journal of Affective Disorders, 70(1), 27–33.
Gorman, J. M., Kent, J. M., Sullivan, G. M. & Coplan, J. D. (2000). Neuroanatomical hypothesis of panic disorder, revised. American Journal of Psychiatry, 157(4), 493–505.
Gould, R. A., Otto, M. & Pollack, M. (1995). A meta-analysis of treatment outcome for panic disorder. Clinical Psychology Review, 15, 819–44.
Greenberg, P. E., Sisitsky, T., Kessler, R. al. (1999). The economic burden of anxiety disorders in the 1990s. Journal of Clinical Psychiatry, 60(7), 427–35.
Heldt, E. M., Gisele, G., Kipper, L., Blaya, C., Isolan, L. & Otto, M. W. (2006). One-year follow-up of pharmacotherapy-resistant patients with panic disorder treated with cognitive-behavior therapy: Outcome and predictors of remission. Behaviour Research and Therapy, 44(5), 657–65.
Hope, D. A., Rapee, R. M., Heimberg, R. G. & Dombeck, M. J. (1990). Representations of the self in social phobia: vulnerability to social threat. Cognitive Therapy and Research, 14(2), 177–89.
Isensee, B., Wittchen, H. U., Stein, M. B., Hofler, M. & Lieb, R. (2003). Smoking increases the risk of panic: findings from a prospective community study. Archives in General Psychiatry, 60(7), 692–700.
Jacob, R. G., Furman, J. M., Clark, D. B. & Durrant, J. D. (1992). Vestibular symptoms, panic, and phobia: overlap and possible relationships. Annals of Clinical Psychiatry, 4(3), 163–74.
Kampman, M., Keijsers, G. P. J., Hoogduin, C. A. L. & Hendriks, G.-J. (2002). A randomized, double-blind, placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitive-behavioral therapy alone. Journal of Clinical Psychiatry, 63(9), 772–7.
Katon, W., Russo, J., Sherbourne, al. (2006). Incremental cost-effectiveness of a collaborative care intervention for panic disorder. Psychological Medicine, 36(3), 353–63.
Katschnig, H. & Amering, M. (1998). The long-term course of panic disorder and its predictors. Journal of Clinical Psychopharmacology, 18(6 Suppl. 2), 6S–11S.
Kenardy, J. A., Dow, M. G., Johnston, D. W., Newman, M. G., Thomson, A. & Taylor, C. B. (2003). A comparison of delivery methods of cognitive-behavioral therapy for panic disorder: an international multicenter trial. Journal of Consulting and Clinical Psychology, 71(6), 1068–75.
Kenardy, J. R. S. & Dob, R. (2005) Cognitive behaviour therapy for panic disorder: long-term follow-up. Cognitive Behaviour Therapy, 34(2), 75–8.
Kenardy, J. M. K. & Rosa, V. (2006). Internet-delivered indicated prevention for anxiety disorders: six-month follow-up. Clinical Psychologist, 10(1), 39–42.
Kendler, K. S. (2005). “A gene for” the nature of gene action in psychiatric disorders. American Journal of Psychiatry, 162(7), 1243–52.
Kent, J. M. & Rauch, S. L. (2003). Neurocircuitry of anxiety disorders. Current Psychiatry Reports, 5(4), 266–73.
Kent, J. M., Coplan, J. D., Mawlawi, al. (2005). Prediction of panic response to a respiratory stimulant by reduced orbitofrontal cerebral blood flow in panic disorder. American Journal of Psychiatry, 162(7), 1379–81.
Kessler, R., Stang, P., Wittchen, H., Ustun, B., Roy-Byrne, P. & Walters, E. (1998). Lifetime panic-depression comorbidity in the national comorbidity survey. Archives of General Psychiatry, 55, 801–8.
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R. and Walters, E. E. (2005a). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives in General Psychiatry, 62(6), 593–602.
Kessler, R. C., Chiu, W. T., Demler, O., Merikangas, K. R. & Walters, E. E. (2005b). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives in General Psychiatry, 62(6), 617–27.
Kessler, R. C., Chiu, W. T., Jin, R., Ruscio, A. M., Shear, K. & Walters, E. E. (2006). The Epidemiology of Panic Attacks, Panic Disorder, and Agoraphobia in the National Comorbidity Survey Replication. Archives of General Psychiatry, 63, 415–24.
Krystal, J. H., Deutsch, D. N. & Charney, D. S. (1996). The biological basis of panic disorder. Journal of Clinical Psychiatry, 57 (Suppl. 10), 23–31; discussion 32–3.
McNally, R. J. (2002). Anxiety sensitivity and panic disorder. Biological Psychiatry, 52(10), 938–46.
Marks, I. M., Swinson, R. P., Basoglu, al. (1993). Alprazolam and exposure alone and combined in panic disorder with agoraphobia. A controlled study in London and Toronto. British Journal of Psychiatry, 162, 776–87.
Marks, I. M., Kenwright, M., McDonough, M., Whittaker, M. & Mataix-Cols, D. (2004). Saving clinicians' time by delegating routine aspects of therapy to a computer: a randomized controlled trial in phobia/panic disorder. Psychological Medicine, 34(1), 9–17.
Massana, G., Gasto, C., Junque, al. (2002). Reduced levels of creatine in the right medial temporal lobe region of panic disorder patients detected with (1)H magnetic resonance spectroscopy. Neuroimage, 16(3 Pt 1), 836–42.
Massana, G., Serra-Grabulosa, J. M., Salgado-Pineda, al. (2003). Amygdala atrophy in panic disorder patients detected by volumetric magnetic resonance imaging. Neuroimage, 19(1), 80–90.
Mitte, K. (2005). A meta-analysis of the efficacy of psycho- and pharmacotherapy in panic disorder with and without agoraphobia. Journal of Affective Disorders, 88(1), 27–45.
Neumeister, A., Bain, E., Nugent, A. al. (2004). Reduced serotonin type 1 A receptor binding in panic disorder. Journal of Neuroscience, 24(3), 589–91.
NICE (2004). Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. London: National Collaborating Centre for Primary Care. (
Norton, C. R., Cox, B. J. & Malan, J. (1992). Nonclinical panickers: a critical review. Clinical Psychology Review, 12, 121–39.
Noyes, R. Jr, Anderson, D. J., Clancy, al. (1984). Diazepam and propranolol in panic disorder and agoraphobia. Archives in General Psychiatry, 41(3), 287–92.
Otto, M. W., Tuby, K. S., Gould, R. A., McLean, R. Y. & Pollack, M. H. (2001). An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder. American Journal of Psychiatry, 158(12), 1989–92.
Pignone, M. P., Gaynes, B. N., Rushton, J. al. (2002). Screening for depression in adults: a summary of the evidence for the U.S. Preventive Services Task Force. Annales of Internal Medicine, 136(10), 765–76.
Pitts, F. N. Jr. & McClure, J. N. Jr (1967). Lactate metabolism in anxiety neurosis. New England Journal of Medicine, 277(25), 1329–36.
Pollack, M. H., Allgulander, C., Bandelow, al. (2003). WCA recommendations for the long-term treatment of panic disorder. CNS Spectrums, 8(8 (Suppl. 1), 17–30.
Proudfoot, J., Ryden, C., Everitt, al. (2004). Clinical efficacy of computerised cognitive-behavioural therapy for anxiety and depression in primary care: randomised controlled trial. British Journal of Psychiatry, 185, 46–54.
Reiss, S. (1980). Pavlovian conditioning and human fear: an expectancy model. Behavior Therapy, 11(3), 380–96.
Rickels, K., Schweizer, E., Weiss, S. & Zavodnick, S. (1993). Maintenance drug treatment for panic disorder. II. Short- and long-term outcome after drug taper. Archives of General Psychiatry, 50(1), 61–8.
Rollman, B. L., Belnap, B. H., Reynolds, C. F., Schulberg, H. C. & Shear, M. K. (2003). A contemporary protocol to assist primary care physicians in the treatment of panic and generalized anxiety disorders. General Hospital Psychiatry, 25, 74–82.
Rosenbaum, J. F., Biederman, J., Hirshfeld-Becker, D. al. (2000). A controlled study of behavioral inhibition in children of parents with panic disorder and depression. American Journal of Psychiatry, 157(12), 2002–10.
Roth, M. (1984). Agoraphobia, panic disorder and generalized anxiety disorder: some implications of recent advances. Psychiatric Developments, 2(1), 31–52.
Roy-Byrne, P. P. & Cowley, D. S. (1995). Course and outcome in panic disorder: A review of recent follow-up studies. Anxiety, 1, 151–60.
Roy-Byrne, P. P., & Cowley, D. (2002). Pharamcologic treatments for panic disorder, generalized anxiety disorder, specific phobia and social anxiety disorders. In A Guide to Treatments that Work, ed. Nathan, P. E. and Gorman, J., pp. 337–65. New York: Oxford University Press.
Roy-Byrne, P. P., Geraci, M. & Uhde, T. W. (1986). Life events and the onset of panic disorder. American Journal of Psychiatry, 143(11), 1424–7.
Roy-Byrne, P. P., Stein, M. B., Russo, al. (1999). Panic disorder in the primary care setting: comorbidity, disability, service utilization, and treatment. Journal of Clinical Psychiatry, 60(7), 492–9.
Roy-Byrne, P. P., Katon, W., Cowley, D. al. (2000). Panic disorder in primary care: Biopsychosocial differences between recognized and unrecognized patients. General Hospital Psychiatry, 22, 405–11.
Roy-Byrne, P. P., Katon, W. J., Cowley, D. S. & Russo, J. (2001). A randomized trial of collaborative care for patients with panic disorder in primary care. Archives of General Psychiatry, 58, 869–76.
Roy-Byrne, P. P., Craske, M. G., Stein, M. al. (2005). A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder. Archives of General Psychiatry, 62(3), 290–8.
Roy-Byrne, P. P., Craske, M. G. & Stein, M. B. (2006). Panic disorder. Lancet, 368, 1023–32.
Sakai, Y., Kumano, H., Nishikawa, al. (2005). Cerebral glucose metabolism associated with a fear network in panic disorder. Neuroreport, 16(9), 927–31.
Sheehan, D. V., Davidson, J., Manschreck, T. & Fleet, Wyck J. (1983). Lack of efficacy of a new antidepressant (bupropion) in the treatment of panic disorder with phobias. Journal of Clinical Psychopharmacology, 3(1), 28–31.
Sheehan, D. V., Raj, A. B., Harnett-Sheehan, K., Soto, S. & Knapp, E. (1993). The relative efficacy of high-dose buspirone and alprazolam in the treatment of panic disorder: a double-blind placebo-controlled study. Acta Psychiatrica Scandinavica, 88(1), 1–11.
Sibille, E., Pavlides, C., Benke, D. & Toth, M. (2000). Genetic inactivation of the Serotonin(1A) receptor in mice results in downregulation of major GABA(A) receptor alpha subunits, reduction of GABA(A) receptor binding, and benzodiazepine-resistant anxiety. Journal of Neuroscience, 20(8), 2758–65.
Smits, J. A. J. O. C., Conall, M. & Otto, M. W. (2006). Combining cognitive-behavioral therapy and pharmacotherapy for the treatment of panic disorder. Journal of Cognitive Psychotherapy, 20(1), 75–84.
Stein, M. B., Walker, J. R., Anderson, al. (1996). Childhood physical and sexual abuse in patients with anxiety disorders and in a community sample. American Journal of Psychiatry, 153(2), 275–7.
Stein, M. B., Norton, G. R., Walker, J. R., Chartier, M. J. & Graham, R. (2000). Do SSRIs enhance the efficacy of very brief cognitive behavioral therapy for panic disorder? A pilot study. Psychiatry Research, 94, 191–200.
Stein, M. B., Sherbourne, C. D., Craske, M. al. (2004). Quality of care for primary care patients with anxiety disorders. American Journal of Psychiatry, 161(12), 2230–7.
Swinson, R. P., Soulios, C., Cox, B. J. & Kuch, K. (1992). Brief treatment of emergency room patients with panic attacks. American Journal of Psychiatry, 149(7), 944–6.
Telch, M. & Lucas, R. (1994). Combined pharmacological and psychological treatment of panic disorder: current status and future directions. In Treatment of Panic/Disorder: A Consensus Development Conference. American Psychiatric Press.
Telch, M. J., Schmidt, N. B., Jaimez, T. L., Jacquin, K. M. & Harrington, P. J. (1995). Impact of cognitive-behavioral treatment on quality of life in panic disorder patients. Journal of Consulting Clinical Psychology, 63(5), 823–30.
Trivedi, M., Fava, M., Wisniewski, S. al. (2006). Augmentation after the Failure of SSRIs for Depression. New England Journal of Medicine, 354(12), 1243–52.
Tsao, J. C. I., Mystkowski, J., Zucker, B. & Craske, M. G. (2002). Effects of cognitive-behavioral therapy for panic disorder on comorbid conditions: replication and extension. Behavior Therapy, 33, 493–509.
Uchida, R. R., Del-Ben, C. M., Santos, A. al. (2003). Decreased left temporal lobe volume of panic patients measured by magnetic resonance imaging. Brazilian Journal of Medical and Biological Research, 36(7), 925–9.
Wang, P. S., Berglund, P. & Kessler, R. C. (2000). Recent care of common mental disorders in the United States: prevalence and conformance with evidence-based recommendations. Journal of General Internal Medicine, 15(5), 284–92.
Watanabe, A., Nakao, K., Tokuyama, M. & Takeda, M. (2005). Prediction of first episode of panic attack among white-collar workers. Psychiatry and Clinical Neuroscience, 59(2), 119–26.
Westen, D. & Morrison, K. (2001). A multidimensional meta-analysis of treatments for depression, panic, and generalized anxiety disorder: an empirical examination of the status of empirically supported therapies. Journal of Consulting Clinical Psychology, 69(6), 875–99.
Wittchen, H. U., Reed, V. & Kessler, R. C. (1998). The relationship of agoraphobia and panic in a community sample of adolescents and young adults. Archives of General Psychiatry, 55(11), 1017–24.
Young, A. S., Klap, R., Sherbourne, C. D. & Wells, K. B. (2001). The quality of care for depressive and anxiety disorders in the United States. Archives of General Psychiatry, 58(1), 55–61.
Zimmermann, P., Wittchen, H. U., Hofler, M., Pfister, H., Kessler, R. C. & Lieb, R. (2003). Primary anxiety disorders and the development of subsequent alcohol use disorders: a 4-year community study of adolescents and young adults. Psychological Medicine, 33(7), 1211–22.