Biology and Pharmacological Treatment of Panic Disorder

  • T. W. Uhde
  • M. B. Stein


Considerable controversy exists regarding the etiologic nature of panic disorder. Predictably, proponents of psychological therapies posit psychological and experiential origins for panic disorder, while believers in psychopharmacological approaches put forward biological explanations. Who is correct?


Panic Disorder Panic Attack Dexamethasone Suppression Test Panic Disorder Patient Bioi Psychiatry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd ed, revised. American Psychiatric Association, WashingtonGoogle Scholar
  2. Amsterdam JD, Maislin G, Winokur A, Kling M, Gold P (1987) Pituitary and adrenocortical responses to the ovine corticotropin releasing hormone in depressed patients and healthy volunteers. Arch Gen Psychiatry 44: 775–781PubMedGoogle Scholar
  3. Arana GW, Baldessarini RJ, Ornsteen M (1985) The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Arch Gen Psychiatry 42: 1193–1204PubMedGoogle Scholar
  4. Avery DH, Osgood TB, Ishiki DM, Wilson LG, Kenny M, Dunner DL (1985) The DST in psychiatric outpatients with generalized anxiety disorder, panic disorder or primary affective disorder. Am J Psychiatry 139: 287–291Google Scholar
  5. Ballenger JC, Peterson GA, Laraia M, Hucek A, Lake CR, Jimerson D, Cox D, Trockman C, Shipe JR Jr, Wilkinson C (1984) A study of plasma catecholamines in agoraphobia and the relationship of serum tricyclic levels to treatment response. In: Ballenger JC (ed) Biology of agoraphobia. American Psychiatric Press, Washington, pp 28–63Google Scholar
  6. Beaudry P, Fontaine R, Chouinard G, Annable L (1986) Clonazepam in the treatment of patients with recurrent panic attacks. J Clin Psychiatry 47: 83–85PubMedGoogle Scholar
  7. Beck AT, Emery GD (1985) Anxiety disorders and phobias: a cognitive perspective. Basic, New YorkGoogle Scholar
  8. Boulenger J-P, Uhde TW, Wolff EA, Post RM (1984) Increased sensitivity to caffeine in patients with panic disorders: preliminary evidence. Arch Gen Psychiatry 41: 1067–1071PubMedGoogle Scholar
  9. Boulenger J-P, Salem N Jr, Marangos PJ, Uhde TW (1987) Plasma adenosine levels: measurement in humans and relationship to the anxiogenic effects of caffeine. Psychiatry Res 21: 247–255PubMedCrossRefGoogle Scholar
  10. Breier A, Albus M, Pickar D, Zahn TP, Wolkowitz OM, Paul SM (1987) Controllable and uncontrollable stress in humans: alterations in mood and neuroendocrine and psychophysiological function. Am J Psychiatry 144: 1410–1425Google Scholar
  11. Bridges M, Yeragani VK, Rainey JM, Pohl R (1986) Dexamethasone suppression test in patients with panic attacks. Biol Psychiatry 21: 853–855PubMedCrossRefGoogle Scholar
  12. Byrne S (1987) Verapamil in the treatment of irritable bowel syndrome (letter). J. Clin Psychiatry 48: 388PubMedGoogle Scholar
  13. Cameron OG, Smith CB, Hollingsworth PJ, Nesse RM, Curtis GC (1984) Platelet alpha-2adrenergic receptor binding and plasma catecholamines. Arch Gen Psychiatry 41: 1144–1148PubMedGoogle Scholar
  14. Casper RC, Frohman LA (1982) Delayed TSH release in anorexia nervosa following injection of thyrotropin-releasing hormone (TRH). Psychoneuroendocrinology 7: 59–68PubMedCrossRefGoogle Scholar
  15. Carroll BJ (1984) Dexamethasone suppression test. In: Hall RCW, Beresford TPP (eds) Handbook of psychiatric diagnostic procedures. Spectrum, Jamaica, vol 1, pp 3–28Google Scholar
  16. Charney DS, Heninger GR (1986) Abnormal regulation of noradrenergic function in panic disorders: effects of clonidine in healthy subjects and patients with agoraphobic and panic disorder. Arch Gen Psychiatry 43: 1042–1054PubMedGoogle Scholar
  17. Charney DS, Heninger GR, Jatlow PI (1985) Incdreased anxiogenic effects of caffeine in panic disorders. Arch Gen Psychiatry 42: 233–243PubMedGoogle Scholar
  18. Charney DS, Woods SW, Goodman WK, Krystal JH, Nagy LM, Heninger GR (1987) The efficacy of lorazepam in panic disorders. New Research Abstract 165. 140th Annual meeting of the American Psychiatric Association, Chicago, May 13, 1987Google Scholar
  19. Chouinard G, Annable L, Fontaine R, Solyom L (1982) Alprazolam in the treatment of generalized anxiety and panic disorders: a double-blind placebo-controlled study. Psychopharmacology (Berlin) 7: 229–233CrossRefGoogle Scholar
  20. Clark DM (1986) A cognitive approach to panic. Behav Res Ther 24: 461–470PubMedCrossRefGoogle Scholar
  21. Coryell WM, Noyes R Jr, Clancy J, Crowe R, Chaudhry D (1985) Abnormal escape from dexamethasone suppression in agoraphobia with panic attacks. Psychiatry Res 15: 301–311PubMedCrossRefGoogle Scholar
  22. Crowe RR, Noyes R, Pauls DL, Slymen D (1983) A family study of panic disorder. Arch Gen Psychiatry 40: 1065–1069PubMedGoogle Scholar
  23. Curtis GC, Nesse R, Buxton M, Lippman D (1978) Anxiety and plasma cortisol at the crest of the circadian cycle; reappraisal of a classical hypothesis. Psychosom Med 40: 368–378PubMedGoogle Scholar
  24. Curtis GC, Cameron OG, Nesse RM (1982) The dexamethasone suppression test in panic disorder and agoraphobia. Am J Psychiatry 139: 1043–1046PubMedGoogle Scholar
  25. Daly JW (1983) Role of ATP and adenosine receptors in physiologic process: summary and prospectus. In: Daly JW, Kuroda Y, Phillis JW, Shimizu H, Ui M (eds) Physiology and pharmacology of adenosine derivatives. Raven, New York, p 275Google Scholar
  26. Edlund MJ, Swann AC, Clothier J (1987) Patients with panic attacks and abnormal EEG results. Am J Psychiatry 144: 508–509PubMedGoogle Scholar
  27. Frohlich ED (1985) Role of calcium entry-blocking drugs in hypertension: a symposium. Am J Cardiol 56:1H–111HCrossRefGoogle Scholar
  28. Fyer AJ, Liebowitz MR, Gorman JM (1987) Discontinuation of alprazolam treatment in panic patients. Am J Psychiatry 144: 303–308PubMedGoogle Scholar
  29. Garbutt JC, Loosen PT, Tipermas A, Prange AJ Jr (1983) The TRH test in patients with borderline personality disorder. Psychiatry Res 9: 107–113PubMedCrossRefGoogle Scholar
  30. Gold PW, Loriaux LD, Roy A, Kling MA, Calabrese JR, Kellner CH, Nieman LK, Post RM, Pickar D, Gallucci W, Avgerinos P, Paul S, Oldfield EH, Cutler GB, Chrousos GP (1986) The corticotropin releasing factor stimulation test: implications for the diagnosis and pathophysiology of hypercortisolism in primary affective disorder and Cushing’s disease. N Engl J Med 314–1329–1335Google Scholar
  31. Goldstein AJ, Chambless DL (1978) A reanalysis of agoraphobia. Behav Ther 9: 47–59CrossRefGoogle Scholar
  32. Goldstein S, Halbreich U, Asnis G, Endicott J, Alvir J (1987) The hypothalamic-pituitary-adrenal system in panic disorder. Am J Psychiatry 144: 1320–1323PubMedGoogle Scholar
  33. Gorman JM, Fyer MR, Liebowitz MR, Klein DF (in press) Pharmacologic provocation of panic attacks. Am J PsychiatryGoogle Scholar
  34. Grunhaus L, Rabin D, Greden F (1986) Simultaneous panic and depressive disorder; response to antidepressant treatments. J Clin Psychiatry 47: 4–7PubMedGoogle Scholar
  35. Gwirtsman HE, Roy-Byrne PP, Yager J, Gerner RH (1983) Neuroendocrine abnormalities in bulimia. Am J Psychiatry 140: 559–563PubMedGoogle Scholar
  36. Hibbert GA (1984) Ideational components of anxiety. Br J Psychiatry 144: 618–624PubMedCrossRefGoogle Scholar
  37. Kahn RJ, McNair DM, Frankenthaler LM (1987) Tricyclic treatment of generalized anxiety disorder. J Affective Disord 13: 145–151CrossRefGoogle Scholar
  38. Klein DF (1964) Delineation of two drug-responsive anxiety syndromes. Psychopharmacologia 5: 397–408PubMedCrossRefGoogle Scholar
  39. Klein DF (1967) Importance of psychiatric diagnoses in prediction of clinical drug effects. Arch Gen Psychiatry 16: 118–126PubMedGoogle Scholar
  40. Klein DF (1981) Anxiety reconceptualized. In: Klein DF, Rabkin JG (eds) Anxiety: new research and changing concepts. Raven, New YorkGoogle Scholar
  41. Klein E, Uhde TW (in press) Verapamil in the treatment of panic disorder: a controlled study. Am J PsychiatryGoogle Scholar
  42. Klein E, Uhde TW, Post RM (1986) Preliminary evidence for the utility of carbamazepine in alprazolam withdrawal. Am J Psychiatry 143: 235–236PubMedGoogle Scholar
  43. Klein DF, Ross DC, Cohen P (1987) Panic and avoidance in agoraphobia: application of path analysis to treatment studies. Arch Gen Psychiatry 44: 377–385PubMedGoogle Scholar
  44. Koenigsberg HW, Pollak C, Sullivan T (1987) The sleep lactate infusion: arousal and the panic mechanism. Biol Psychiatry 22: 789–791PubMedCrossRefGoogle Scholar
  45. Lieberman JA, Brenner R, Lesser M, Coccaro E, Berenstein M, Kane JM (1983) Dexamethasone suppression tests in patients with panic disorder. Am J Psychiatry 140: 917–919PubMedGoogle Scholar
  46. Liebowitz MR, Fyer AJ, Gorman JM, Dillon D, Appleby IL, Levy G, Anderson S, Levitt M, Palij M, Davies SO, Klein DF (1984a) Lactate provocation of panic attacks: I. Clinical and Biology and Pharmacological Treatment of Panic Disorder 33 behavioral findings. Arch Gen Psychiatry 41: 764–770Google Scholar
  47. Liebowitz MR, Quitkin FM, Stewart JW, McGrath PJ, Harrison W, Rabkin J, Tricamo E, Markowitz JS, Klein DF (1984b) Penelzine versus imipramine in atypical depression: a preliminary report. Arch Gen Psychiatry 41: 669–677Google Scholar
  48. Liebowitz MR, Gorman JM, Fyer AJ, Levitt M, Dillon D, Levy G, Appleby IL, Anderson S, Palij M, Davies S, Klein DF (1985) Lactate provocation of panic attacks: II. Biochemical and physiological findings. Arch Gen Psychiatry 42: 709–719PubMedGoogle Scholar
  49. Loosen PT (1985) The TRH-induced TSH response in psychiatric patients: A possible neuroendocrine marker. Psychoneuroendocrinology 10: 237–260PubMedCrossRefGoogle Scholar
  50. Loosen PT, Prange AJ Jr (1982) Serum thyrotropin response to thyrotropin-releasing hormone in psychiatric patients; a review. Am J Psychiatry 139: 405–416PubMedGoogle Scholar
  51. Loosen PT, Prange AJ, Wilson IC (1979) TRH (protirelin) in depressed alcoholic men: behavioral changes and endocrine responses. Arch Gen Psychiatry 36: 540–547PubMedGoogle Scholar
  52. Lydiard RB (1987) Desipramine in agoraphobia with panic attacks: an open, fixed-dose study. J Clin Psychopharmacol 7: 258–260PubMedGoogle Scholar
  53. Lydiard RB, Ballenger JC (1987) Antidepressants in panic disorder and agoraphobia. J Aff Disord 13: 153–168CrossRefGoogle Scholar
  54. Lydiard RB, Laraia MT, Howell EF, Ballenger JC (1987) Emergence of depressive symptoms in patients receiving alprazolam for panic disorder. Am J Psychiatry 144: 664–665PubMedGoogle Scholar
  55. Marangos PJ, Boulenger J-P (1985) Basic and clinical aspects of adenosinergic neuromodulation. Neurosci Biobehav Rev 9: 421–430PubMedCrossRefGoogle Scholar
  56. Margraf J, Ehlers A, Roth WT (1986a) Sodium lactate infusions and panic attacks: a review and critique. Psychosom Med 48: 23–51Google Scholar
  57. Margraf J, Ehlers A, Roth WT (1986b) Panic attacks: theoretical models and empirical evidence. In: Hand I, Wittchen H-U (eds) Panic and phobias. Springer, Berlin Heidelberg New YorkGoogle Scholar
  58. Marks IM (1983) Are there anticompulsive or antiphobic drugs? Review of the evidence. Br J Psychiatry 143: 338–347PubMedCrossRefGoogle Scholar
  59. Marks IM (1987) Behavioral aspects of panic disorder. Am J Psychiatry 144: 1160–1165PubMedGoogle Scholar
  60. Marks IM, Gray S, Cohen D, Hill R, Mawson D, Ramm L, Stern RS (1983) Imipramine and brief therapist-aided exposure in agoraphobics having self-exposure homework. Arch Gen Psychiatry 40: 153–162PubMedGoogle Scholar
  61. Mavissakalian M, Barlow DH (eds) (1983) Phobia: psychological and pharmacological treatment. Guilford, New YorkGoogle Scholar
  62. Mavissakalian M, Michelson L (1986) Agoraphobia: relative and combined effectiveness of therapist-assisted in vivo exposure and imipramine. J Clin Psychiatry 47: 117–122PubMedGoogle Scholar
  63. Mavissakalian M, Michelson L, Dealy RS (1983) Pharmacological treatment of agoraphobia. Imipramine versus imipramine with programmed practice. Br J Psychiatry 143: 348–355PubMedCrossRefGoogle Scholar
  64. Mellman TA, Uhde TW (1987a) Obsessive-compulsive symptoms in panic disorder. Am J Psychiatry 144: 1573–1576Google Scholar
  65. Mellman TA, Uhde TW (1987b) Withdrawal syndrome with gradual tapering of alprazolam. Am J Psychiatry 143: 1464–1466Google Scholar
  66. Mellman TA, Uhde TW (1988) Electroencephalographic sleep in panic disorder: a focus on sleep-related panic attacks. Submitted for publicationGoogle Scholar
  67. Nesse RM, Cameron OG, Curtis GC, McCann DS, Huber-Smith MJ (1984) Adrenergic function in patients with panic anxiety. Arch Gen Psychiatry 41: 771–776PubMedGoogle Scholar
  68. Noyes R Jr, Clarkson C, Crowe RR, Yates WR, Mohesney CM (1987) A family study of generalized anxiety disorder. Am J Psychiatry 144: 1019–1024PubMedGoogle Scholar
  69. Peabody CA, Whiteford HA, Warner MD, Faull KF, Barchas JD, Berger PA (1987) TRH stimulation test in depression. Psych Res 22: 21–28CrossRefGoogle Scholar
  70. Peterson GA, Ballenger JC, Cox DP, Hucek A, Lydiard RB, Laraia MT, Trockman C (1985) The dexamethasone suppression test in agoraphobia. J Clin Psychopharmacol 5: 110–102CrossRefGoogle Scholar
  71. Pitts FN Jr, McClure JN (1967) Lactate metabolism in anxiety neurosis. N Engl J Med 277: 1329–1336PubMedCrossRefGoogle Scholar
  72. Redmond D Jr, Huang Y (1983) Current concepts II. New evidence for a locus coeruleus-norepinephrine connection with anxiety. Life Sci 25: 2149–2162CrossRefGoogle Scholar
  73. Reiman EM, Raichle ME, Robins E, Butler FK, Herscovitch P, Fox P, Perlmutter J (1986) The application of positron emission tomography to the study of panic disorder. Am J Psychiatry 143: 469–477PubMedGoogle Scholar
  74. Roy-Byrne PP, Uhde TW (in press) Exogenous factors in panic disorder: Clinical and research implications. J Clin PsychiatryGoogle Scholar
  75. Roy-Byrne PP, Bierer LM, Uhde TW (1985) The dexamethasone suppression test in panic disorder: comparison with normal controls. Biol Psychiatry 20: 1237–1240PubMedCrossRefGoogle Scholar
  76. Roy-Byrne PP, Uhde TW, Post RM, Gallucci WM, Chrousos GR (1986a) The corticotropinreleasing hormone stimulation test in patients with panic disorder. Am J Psychiatry 143: 896–899Google Scholar
  77. Roy-Byrne PP, Uhde TW, Rubinow DR, Post RM (1986b) Reduced TSH and prolactin responses to TRH in patients with panic disorder. Am J Psychiatry 143: 503–507Google Scholar
  78. Sachar EJ, Hellman L, Roffwarg HP, Halpern F, Fukashima D, Gallagher T (1973) Disrupted 24-hour patterns of cortisol secretion in psychotic depression. Arch Gen Psychiatry 28: 19–24PubMedGoogle Scholar
  79. Sheehan DV (1982) Panic attacks and phobias. N Engl J Med 307: 156–158PubMedCrossRefGoogle Scholar
  80. Sheehan DV (1987) Benzodiazepines in panic disorder and agoraphobia. J Affective Disord 13: 169–181CrossRefGoogle Scholar
  81. Sheehan DV, Ballenger JC, Jacobson G (1980) Treatment of endogenous anxiety with phobic, hysterical and hypochondriacal symptoms. Arch Gen Psychiatry 37: 51–59PubMedGoogle Scholar
  82. Sheehan DV, Claycomb JB, Surman OS, Baer L, Coleman J, Gelles L (1983) Panic attacks and the dexamethasone suppression test. Am J Psychiatry 140: 1063–1064PubMedGoogle Scholar
  83. Siever LJ, Uhde TW (1984) New studies and perspectives on the noradrenergic receptor system in depression: effects of the alpha-2adrenergic agonist clonidine. Biol Psychiatry 19: 131–156PubMedGoogle Scholar
  84. Solomon GD, Steel JG, Spaccavento LJ (1983) Verapamil prophylaxis of migraine: a double-blind, placebo-controlled study. JAMA 250: 2500–2502PubMedCrossRefGoogle Scholar
  85. Solyom C, Solyom L, Lapierre Y, Pecknold J, Morton L (1981) Phenelzine and exposure in the treatment of phobias. Biol Psychiatry 16: 239–247PubMedGoogle Scholar
  86. Spier SA, Tesar GE, Rosenbaum JF, Woods SW (1986) Treatment of panic disorder and agoraphobia with clonazepam. J Clin Psychiatry 47: 238–242PubMedGoogle Scholar
  87. Stein MB, Uhde TW (1988) Thyroid indices in panic disorder. Submitted for publicationGoogle Scholar
  88. Stein MB, Uhde TW (in press) Panic disorder and major depression: Lifetime relationship and biological markers. In: Ballenger JC (ed) Neurobiological aspects of panic disorder. Liss, New YorkGoogle Scholar
  89. Telch MJ, Agras WS, Taylor B, Roth WT, Gallen CC (1985) Combined pharmacological and behavioral treatment for agoraphobia. Behav Res Ther 23: 325–335PubMedCrossRefGoogle Scholar
  90. Torgerson S (1983) Genetic factors in anxiety disorders. Arch Gen Psychiatry 40: 1085–1092Google Scholar
  91. Uhde TW (1986) Treating panic and anxiety. Psychiatr Ann 16: 536–541Google Scholar
  92. Uhde TW (in press) Caffeine: Practical facts for the psychiatrist. In: Roy-Byrne PP (ed) Anxiety: new research findings for the clinician. APA Press, Washington, DCGoogle Scholar
  93. Uhde TW, Boulenger J-P (in press) Caffeine model of panic. In: Lerer B, Gershon S (eds) New directions in affective disordersGoogle Scholar
  94. Uhde TW, Nemiah JC (in press) Panic and generalized anxiety disorders. In: Kaplan HI, Sadock BJ (eds) Comprehensive textbook of psychiatry, 5th ed. Williams and Wilkins, BaltimoreGoogle Scholar
  95. Uhde TW, Tancer ME (in press) Pharmacological challenge paradigms in panic disorder. In: Tyrer P (ed) Proceedings of the British Association for Psychopharmacology symposium on anxiety. Oxford University Press, London Google Scholar
  96. Uhde TW, Boulenger J-P, Post RM, Siever LJ, Vittone BJ, Jimerson DC, Roy-Byrne PP (1984) Fear and anxiety: relationship to noradrenergic function. Psychopathology 17 (Suppl 3): 8–23PubMedCrossRefGoogle Scholar
  97. Uhde TW, Ballenger JC, Post RM (1985a) Carbamazepine: Treatment of affective illness and anxiety syndromes. In: Pichot P, Berner P, Wolf R, Than K (eds) Psychiatry: the state of the art, vol 3. Plenum, New York, pp 474–484Google Scholar
  98. Uhde TW, Boulenger J-P, Roy-Byrne PP, Geraci MF, Vittone BJ, Post RM (1985b) longitudinal course of panic disorder: clinical and biological considerations. Prog Neuropsychopharmacol Biol Psychiatry 9:39–51CrossRefGoogle Scholar
  99. Uhde TW, Roy-Byrne P, Post RM (1986a) Panic disorder and major depressive disorder: biological relationship. In: Shagass C, Josiassen RC, Bridger WH, Weiss KJ, Stoff D, Simpson GM (eds) Biological psychiatry 1985. Elsevier, New York, pp 463–465Google Scholar
  100. Uhde TW, Vittone BJ, Siever LJ, Kaye WH, Post RM (1986b) Blunted growth hormone response to clonidine in panic disorder patients. Biol Psychiatry 21: 1081–1085CrossRefGoogle Scholar
  101. Uhde TW, Stein MB, Post RM (1988a) Lack of efficacy of carbamazepine in the treatment of panic disorder. Submitted for publicationGoogle Scholar
  102. Uhde TW, Stein BM, Vittone BJ, Siever LJ, Boulenger J-P, Klein EM, Mellman TA, Post RM (1988b) Behavioral and physiological effects of acute and chronic response to clonidine in panic disorder. Submitted for publicationGoogle Scholar
  103. Uhde TW, Joffe RT, Jimerson DC, Post RM (in press) Normal urinary-free cortisol and plasma MHPG in panic disorder: clinical and theoretical implications. Biol PsychiatryGoogle Scholar
  104. Visser TJ (1985) Regulation of the release of TSH. Front Horm Res 14: 100–136Google Scholar
  105. Woods SW, Charney DS, Loke J, Goodman WK, Redmond DE, Heninger GR (1986) Carbon dioxide sensitivity in panic anxiety: ventilatory and anxiogenic responses to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment. Arch Gen Psychiatry 43: 900–909PubMedGoogle Scholar
  106. Zitrin CM, Klein DF, Woerner MG (1978) Beha-vior therapy, supportive psychotherapy, imipra-mine and phobias. Arch Gen Psychiatry 35: 307–316 Google Scholar
  107. Zitrin CM, Klein DF, Woerner MG (1980) Trea-ment of agoraphobia with group exposure in vivo and imipra. Arch Gen Psychiatry 37:63–72PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • T. W. Uhde
  • M. B. Stein

There are no affiliations available

Personalised recommendations