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A Risk-Benefit Assessment of Pharmacological Treatments for Panic Disorder

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  • Risk-Benefit Assessment
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Summary

Panic disorder, a psychiatric disorder characterised by frequent panic attacks, is the most common anxiety disorder, affecting 2 to 6% of the general population. No one line of treatment has been found to be superior, making a risk-benefit assessment of the treatments available useful for treating patients. Choice of treatment depends on a number of issues, including the adverse effect profile, efficacy and the presence of concomitant syndromes.

Tricyclic antidepressants (TCAs) are beneficial in the treatment of panic disorder. They have a proven efficacy, are affordable and are conveniently administered. Adverse effects, including jitteriness syndrome, bodyweight gain, anticholinergic effects and orthostatic hypotension are commonly associated with TCAs, but can be managed successfully.

Selective serotonin (5-hydroxytryptamine; 5HT) reuptake inhibitors are also potential first line agents and are well tolerated and effective, with a favourable adverse effects profile. There is little risk in overdose or of anticholinergic effects. Adverse effects include sedation, dyspepsia and headache early in treatment, and sexual dysfunction and increased anxiety, but these can be effectively managed with proper dosage escalation and management.

Benzodiazepines are an effective treatment, providing short-term relief of panic-related symptoms. Patients respond to treatment quickly, providing rapid relief of symptoms. Adverse effects include ataxia and drowsiness, and cognitive and psycho-motor impairment. There are reservations over their first-line use because of concerns regarding abuse and dependence.

Monoamine oxidase inhibitors, because of their adverse effects profile, potential drug interactions, dietary restrictions, gradual onset of effect and overdose risk, are not considered to be first-line agents. They are effective however, and should be considered for patients with refractory disease.

Valproic acid (valproate sodium), while not intensively studied, shows potential for use in panic disorder. More studies are needed in this area before the available data can be confirmed. As a supplement to drug therapy, cognitive behavioural therapy is effective. It is well tolerated, and may be beneficial in certain clinical situations. Its main drawback is the time commitment and effort needed to be made by the patient.

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References

  1. Myers JK, Weissman MM, Tischler GL, et al. Six month prevalence of psychiatric disorders in three communities: 1980–1982. Arch Gen Psychiatry 1984; 41: 959–67

    Article  PubMed  CAS  Google Scholar 

  2. Klein DV. Delineation of two drug responsive anxiety syndromes. Psychopharmacologia 1964; 5: 397–408

    Article  PubMed  CAS  Google Scholar 

  3. Klein DV. Importance of psychiatric diagnosis in prediction of clinical drug effects. Arch Gen Psychiatry 1967; 16: 118–26

    Article  PubMed  CAS  Google Scholar 

  4. Wilkerson G, Balestreri M, Ruggeri M, et al. Meta-analysis of double-blind placebo-controlled trials of antidepressants and benzodiazepines for patients with panic disorders. Psychol Med 1991; 21: 991–8

    Article  Google Scholar 

  5. Zitrin CM, Klein DF, Woerneer MG, et al. Treatment of phobias: I. Comparison of imipramine hydrochloride and placebo. Arch Gen Psychiatry 1983; 40: 125–38

    Article  PubMed  CAS  Google Scholar 

  6. Klerman GL. Drug treatment of panic disorder: comparative efficacy of alprazolam, imipramine, and placebo: cross national collaborative panic study second phase investigators. Br J Psychiatry 1992; 160: 191–202

    Article  Google Scholar 

  7. Den Boer JA, Westenberg HGM, Kamerbeck WDJ, et al. Effect of serotonin uptake inhibitors in anxiety disorders: a doubleblind comparison of clomipramine and fluvoxamine. Int Clin Psychopharmacol 1987; 2: 21–32

    Article  Google Scholar 

  8. Hoffart A, Due-Madsen J, Land B, et al. Clomipramine in the treatment of agoraphobia in patients resistant to behavioral therapy. J Clin Psychiatry 1993; 54: 481–7

    PubMed  CAS  Google Scholar 

  9. Fahy TH, O’Rourke D, Brophy J, et al. The Galway study of panic disorder I: clomipramine and lofepramine in DSM III-R panic disorder: a placebo controlled trial. J Affect Disord 1992; 25: 63–76

    Article  PubMed  CAS  Google Scholar 

  10. Modigh K, Westberg P, Erickson E. Superiority of clomipramine over imipramine in the treatment of panic disorder: a placebo controlled trial. J Clin Psychopharmacol 1992; 12: 251–61

    Article  PubMed  CAS  Google Scholar 

  11. Bahhenger JC, Peterson GA, Laraia M, et al. A study of plasma catecholamines in agoraphobia and the relationship of serum tricyclic levels to treatment response. In: Ballenger JC, editor. Biology of agoraphobia. Washington, DC: American Psychiatric Press, 1984: 28–63

    Google Scholar 

  12. Marks IM, Gray S, Cohen D, et al. Imipramine and brief therapist aided exposure in agoraphobics having self exposure homework. Arch Gen Psychiatry 1983; 40: 153–62

    Article  PubMed  CAS  Google Scholar 

  13. Nesse RM, Cameron OG, Curtis GC, et al. Adrenergic function in patients with panic anxiety. Arch Gen Psychiatry 1984; 41: 771–6

    Article  PubMed  CAS  Google Scholar 

  14. Mavissakalian M, Perel JM. Protective effects of imipramine maintenance treatment in panic disorder with agoraphobia. Am J Psychiatry 1992; 149: 1053–7

    PubMed  CAS  Google Scholar 

  15. Clark DM, Salkovskis DM, Hackman A, et al. A comparison of cognitive therapy applied relaxation and imipramine in the treatment of panic disorder. Br J Psychiatry 1994; 164: 759–69

    Article  PubMed  CAS  Google Scholar 

  16. Mavissakalian M, Perel JM. Clinical experiments in maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia. Arch Gen Psychiatry 1992; 49: 318–23

    PubMed  CAS  Google Scholar 

  17. Sheehan DV, Ballenger J, Jacobson G. Treatment of endogenous anxiety with phobic, hysterical and hypochondriacal symptoms. Arch Gen Psychiatry 1980; 37: 51–9

    Article  PubMed  CAS  Google Scholar 

  18. Keller MB, Lavori PW, Goldenberg IM, et al. Influence of depression on the treatment of panic disorder with imipramine, alprazolam, and placebo. J Affect Disord 1993; 28: 27–38

    Article  PubMed  CAS  Google Scholar 

  19. Schweizer E, Rickeis K, Weiss S, et al. Maintenance drug treatment of panic disorder I: results of a prospective, placebo controlled comparison of alprazolam and imipramine. Arch Gen Psychiatry 1993; 50: 51–60

    Article  PubMed  CAS  Google Scholar 

  20. Noyes R, Garvey MJ, Cook BL. Problems with tricyclic antidepressant use in patients with panic disorder or agoraphobia: results of a naturalistic follow up study. J Clin Psychiatry 1989; 50: 163–9

    PubMed  Google Scholar 

  21. Ballenger JC. Long-term pharmacologic treatment of panic disorder. J Clin Psychiatry 1991; 52 Suppl.: 18–23

    PubMed  Google Scholar 

  22. Lydiard RB, Ballenger JC. Antidepressants in panic disorder and agoraphobia. J Affect Disord 1987; 13: 153–68

    Article  PubMed  CAS  Google Scholar 

  23. Sheehan DV. Tricyclic antidepressants in the treatment of panic and anxiety disorders. Psychosomatics 1986; 27 Suppl. 11: 10–6

    PubMed  CAS  Google Scholar 

  24. Balon R, Yeragani VK, Pohl R, et al. Changes in appetite and weight during the pharmacological treatment of patients with panic disorder. Can J Psychiatry 1993; 38: 19–22

    PubMed  CAS  Google Scholar 

  25. Louie AK, Lewis TB, Lannon RA. Use of low dose fluoxetine in major depression and panic disorder. J Clin Psychiatry 1993; 54: 435–8

    PubMed  CAS  Google Scholar 

  26. Schatzberg AF, Ballenger JC. Decisions for the clinician in the treatment of panic disorder: When to treat, which treatment to use, and how long to treat. J Clin Psychiatry 1991; 52 Suppl. 2: 26–31

    PubMed  Google Scholar 

  27. Roy-Byrne P, Wingerson D, Cowley D, et al. Psychopharmacologic treatment of panic, generalized anxiety disorder and social phobia. Psychiatry Clin North Am 1993; 16: 719–35

    CAS  Google Scholar 

  28. Caplan JD, Gorman JM, Klein DF. Serotonin related functions in panic-anxiety: a critical overview. Neuropsychopharmacol 1992; 6: 189–200

    Google Scholar 

  29. Den Boer JA, Westenberg HG. Effect of serotonin and noradrenaline uptake inhibitor in panic disorder: a double-blind comparative study with fluvoxamine and maprotiline. Int Clin Psychopharmacol 1988; 3: 59–74

    Article  Google Scholar 

  30. Hoehn-Saric R, McLeod DR, Hipsley PA. Effect of fluvoxamine on panic disorder. J Clin Psychopharmacol 1993; 13: 321–6

    Article  PubMed  CAS  Google Scholar 

  31. Christiansen PE, Judge R, Ohrstrom JK. A double-blind, placebo-controlled parallel group study of paroxetine in combination with psychotherapy in treatment of patients with panic disorder (DSM III-R) [abstract]. 31st Annual Meeting of American College of Neuropsychopharmacology; 1992 Dec 14–18; San Juan, Puerto Rico: 149

    Google Scholar 

  32. Goddard AW, Woods SW, Sholomskas DE, et al. Effects of serotonin reuptake inhibitor fluvoxamine on yohimbine-induced anxiety in panic disorder. Psychiatry Res 1993; 48: 119–33

    Article  PubMed  CAS  Google Scholar 

  33. Rickels K, Schweizer EE. Benzodiazepines for the treatment of panic attacks: A new look. Psychopharmacol Bull 1986; 22: 93–9

    PubMed  CAS  Google Scholar 

  34. Jefferson WJ. Antidepressants in panic disorder. J Clin Psychiatry 1997; 58 Suppl. 2: 20–4

    PubMed  CAS  Google Scholar 

  35. Marshall JR. Panic disorder: a treatment update. J Clin Psychiatry 1997; 58; 36–42

    Article  PubMed  CAS  Google Scholar 

  36. Black DW, Wesner R, Gabal J. The abrupt discontinuation of fluoxetine in patients with panic disorder. J Clin Psychiatry 1993; 54: 146–9

    PubMed  CAS  Google Scholar 

  37. Gorman JM, Liebowitz MR, Fyer AJ, et al. An open trial of fluoxetine in the treatment of panic attacks. J Clin Psychopharmacol 1987; 7: 329–32

    Article  PubMed  CAS  Google Scholar 

  38. Davidson JRT. Use of benzodiazepines in panic disorder. J Clin Psychiatry 1997; 58 Suppl.2: 26–8

    PubMed  CAS  Google Scholar 

  39. McEvoy GK. AHFS Drug Information. Bethesda (MD): Benzodiazepines, 1955: 1581–606

    Google Scholar 

  40. Uhlenhuth EH, Matuzas W, Glass RM, et al. Response of panic disorder to fixed doses of alprazolam or imipramine. J Affect Disord 1989; 17: 261–70

    Article  PubMed  CAS  Google Scholar 

  41. Herman JB, Rosenbaum JF, Brotman AW. The alprazolam to clonazepam switch for the treatment of panic disorder. J Clin Psychopharmacol 1987; 7: 175–8

    Article  PubMed  CAS  Google Scholar 

  42. Tesar GE, Rosenbaum JF, Pollack MH, et al. Double-blind, placebo controlled comparison of clonazepam and alprazolam for panic disorder. J Clin Psychiatry 1991; 52: 69–76

    PubMed  CAS  Google Scholar 

  43. Tesar GE, Rosenbaum JF. Successful use of clonazepam in patients with treatment-resistant panic disorder. J Nerv Ment Dis 1986; 174: 477–82

    Article  PubMed  CAS  Google Scholar 

  44. Spier SA, Tesar GE, Rosenbaum JF, et al. Treatment of panic disorder and agoraphobia with clonazepam. J Clin Psychiatry 1986; 47: 238–42

    PubMed  CAS  Google Scholar 

  45. Greenblatt DJ, Miller LG, Shader RI. Clonazepam pharmacokinetics, brain uptake, and receptor interactions. J Clin Psychiatry 1987; 48 (10 Suppl.): 4–9

    PubMed  CAS  Google Scholar 

  46. Johnson MR, Lydiard RB, Ballenger JC. Panic disorder: pathophysiology and drug treatment. Drugs 1995; 49: 328–44

    Article  PubMed  CAS  Google Scholar 

  47. Chouinard G, Labonte A, Fontaine R, et al. New concepts in benzodiazepine therapy: rebound anxiety and new indications for more potent benzodiazepines. Prog Neuropsychopharmacol Biol Psychiatry 1983; 7: 669–73

    Article  PubMed  CAS  Google Scholar 

  48. Fontaine R, Chouinard G. Anti-panic effect of clonazepam [letter]. Am J Psychiatry 1984; 141: 149

    PubMed  CAS  Google Scholar 

  49. Beaudry P, Fontaine R, Chouinard G, et al. Clonazepam in the treatment of patients with recurrent panic attacks. J Clin Psychiatry 1986; 47: 83–5

    PubMed  CAS  Google Scholar 

  50. Beckett A, Fishman SM, Rosenbaum JF. Clonazepam blockade of spontaneous and C02 inhalation-provoked panic in a patient with panic disorder. J Clin Psychiatry 1986; 47: 475–6

    PubMed  CAS  Google Scholar 

  51. Pollack MH, Tesar GE, Rosenbaum JF, et al. Clonazepam in the treatment of panic disorder and agoraphobia: A one-year follow-up. J Clin Psychopharmacol 1986; 6: 302–4

    Article  PubMed  CAS  Google Scholar 

  52. Tesar GE, Rosenbaum JF, Pollack MH, et al. Clonazepam versus alprazolam in the treatment of panic disorder: interim analysis of data from a prospective, double-blind, placebocontrolled trial. J Clin Psychiatry 1987; 48 (19 Suppl.): 16–9

    PubMed  Google Scholar 

  53. Uhde TW, Boulenger JP, Roy-Byrne, et al. Longitudinal course of panic disorder: clinical and biological considerations. Prog Neuropsychopharmacol Biol Psychiatry 1985; 9: 39–51

    Article  PubMed  CAS  Google Scholar 

  54. Breier A, Charney DS, Heninger GR. The diagnostic validity of anxiety disorders and their relationship to depressive illness. Am J Psychiatry 1985; 142: 787–97

    PubMed  CAS  Google Scholar 

  55. Lesser IM, Rubin RT, Pecknold JC, et al. Secondary depression in panic disorder and agoraphobia: I: Frequency, severity, and response to treatment. Arch Gen Psychiatry 1988; 81: 830–1

    Google Scholar 

  56. Nikaido AM, Ellinwood EH, Heatherly DG, et al. Age-related increase in CNS sensitivity to benzodiazepines as assessed by task difficulty. Psychopharmacology 1990; 100: 90–7

    Article  PubMed  CAS  Google Scholar 

  57. Lader MH, Ron M, Petursson H. Computerized axial brain tomographic studies following long-term use of benzodiazepines. Psychol Med 1987; 17: 775–7

    Article  Google Scholar 

  58. Roy-Byrne PP, Cowley DS, Greenblatt D, et al. Reduced benzodiazepine sensitivity in panic disorder. Arch Gen Psychiatry 1990; 7: 534–8

    Article  Google Scholar 

  59. Lucki I, Rickels K, Geller AM. Chronic use of benzodiazepines and psychomotor and cognitive test performance. Psychopharmacology 1986; 88: 426–33

    Article  PubMed  CAS  Google Scholar 

  60. DSM TV. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association. 1994 Jul

  61. Ciraulo DA, Barnhill JC, Ciraulo AM, et al. Parental alcoholism as a risk factor in benzodiazepine abuse: a pilot study. Am J Psychiatry 1989; 146: 1333–5

    PubMed  CAS  Google Scholar 

  62. Pecknold JC, Swinson RP, Kuch K, et al. Alprazolam in panic disorder and agoraphobia: discontinuation effects. Arch Gen Psychiatry 1988; 45: 429–36

    Article  PubMed  CAS  Google Scholar 

  63. Pecknold JC. Discontinuation studies: short-term and long-term. Panic and anxiety: a decade of progress: 1990 Jun 19–22; Geneva

    Google Scholar 

  64. Woods SW, Nagy LM, Koleszar AS, et al. Controlled trial of alprazolam supplementation during imipramine treatment of panis disorder. J Clin Psychiatry 1992; 12: 32–8

    CAS  Google Scholar 

  65. Sergant W. The treatment of anxiety states and atypical depression by the monoamine oxidase inhibitor drugs. J Neuropsychiatry 1962; 3: 96–103

    Google Scholar 

  66. Norman TR, Burrows GD. Monamine oxidase, monoamine oxidase inhibitors, and panic disorder. J Neural Transm 1989; 28: 53–63

    CAS  Google Scholar 

  67. West ED, Dally PJ. Effects of iproniazid depressive syndromes. BMJ 1959; 1: 1491–4

    Article  PubMed  CAS  Google Scholar 

  68. Tyres P, Candy D, Kelly D. A study of the clinical effects of phenelzine and placebo in the treatment of phobic anxiety. Psychopharmacologia 1973; 32: 237–54.

    Article  Google Scholar 

  69. Ballenger JC, Sheehan DV, Jacobsen G, et al. Antidepressant treatment of severe phobic anxiety [abstract]. Abstracts of Scientific Proceedings of the 130th Annual Meeting of the American Psychiatric Association: 1977 May 2–6; Toronto, Canada

    Google Scholar 

  70. Mountjoy CQ, Roth M, Gartside RF. A clinical trial of phenelzine in anxiety, depressive and phobic neuroses. Br J Psychiatry 1977; 131: 486–92

    Article  PubMed  CAS  Google Scholar 

  71. Solyom C, Solyom L, LaPierre Y, et al. Phenelzine and exposure in the treatment of phobias. Biol Psychiatry 1981; 16: 239–47

    PubMed  CAS  Google Scholar 

  72. Laird LK, Benefield WH. Mood disorders I: major depressive disorders. In: Young LY, Koda-Kimble MA, editors. Applied therapeutics: the clinical use of drugs. 6th ed. Vancouver, WA: Applied Therapeutics, 1995: 76.1–76.24

    Google Scholar 

  73. Ballenger JC, Lydiard RB, Turner SM. Panic disorder and agoraphobia. In: Gabbard GO, editor. Treatment of psychiatric disorders. 2nd ed. Washington, DC: American Psychiatric Press, Inc, 1995: 1421–52

    Google Scholar 

  74. Rimmer EM, Richens A. An update on sodium valproate. Pharmacotherapy 1985, 5: 171–84

    PubMed  CAS  Google Scholar 

  75. Sanger DJ. Mini review: GABA and the behavioral effects of anxiolytic drugs. Life Sci 1985; 36: 1503–13

    Article  PubMed  CAS  Google Scholar 

  76. Shephard RA. Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action. Life Sci 1987; 40: 2429–36

    Article  PubMed  CAS  Google Scholar 

  77. Penfield W, Jasper H. Epilepsy and the functional anatomy of the human brain. Boston: Little Brown, 1954

    Google Scholar 

  78. Stern TA, Murray GB. Complex partial seizures presenting as a psychiatric illness. J Nerv Ment Dis 1984; 172: 625–7

    Article  PubMed  CAS  Google Scholar 

  79. Roy-Byrne PP. Anticonvulsants in anxiety and withdrawal syndromes: hypotheses for future research. In: McElroy SL, Pope Jr HG, editors. Use of anticonvulsants in psychiatry: recent advances. Clifton (NJ): Oxford Health Care, 1988: 155–68

    Google Scholar 

  80. McElroy SL, Keck Jr PE, Lawrence JL. Treatment of panic disorder and benzodiazepine withdrawal with valproate. J Neuropsychiatry Clin Neurosci 1991; 2: 232–3

    Google Scholar 

  81. Roberts JM, Malcolm R, Santos AB. Treatment of panic disorder and comorbid substance abuse with divalproex sodium [letter]. Am J Psychiatry 1994; 151: 1521

    PubMed  CAS  Google Scholar 

  82. Primeau F, Fontaine R, Beauclair L. Valproic acid and panic disorder. Can J Psychiatry 1990; 35: 248–50

    PubMed  CAS  Google Scholar 

  83. Keck Jr PE, Taylor VE, Tugrul KC, et al. Valproate treatment of panic disorder and lactate-induced panic attacks. Biol Psychiatry 1993; 33: 542–6

    Article  PubMed  Google Scholar 

  84. Keck Jr PE, McElroy SL, Tugrul KC, et al. Antiepileptic drugs for the treatment of panic disorder. Neuropsychobiology 1993; 27: 150–3

    Article  PubMed  Google Scholar 

  85. Woodman CL, Noyes R, Jr. Panic disorder: treatment with valproate. J Clin Psychiatry 1994; 55: 134–6

    PubMed  CAS  Google Scholar 

  86. Lum M, Fontaine R, Elie R, et al. Divalproex sodium antipanic effect in panic disorder: a placebo-controlled study. Biol Psychiatry 1990; 27: 164–5A

    Google Scholar 

  87. Dahlke F, Lohaus A, Gutzmann H. Reliability and clinical concepts underlying global judgements in dementia: implications for clinical research. Pyschopharmacol Bull 1992; 28: 425–32

    CAS  Google Scholar 

  88. Bruss GS, Gruenberg AM, Goldstein RD, et al. Hamilton anxiety rating scale interview guide: joint interview and test-re-test methods for interrater reliability. Psychiatry Res 1994; 53: 191–202

    Article  PubMed  CAS  Google Scholar 

  89. Derogatis LR, Lipman RS, Covi L. SCL-90: an outpatient psychiatric rating scale-preliminary report. Psychopharmacol Bull 1973; 9: 13–28

    PubMed  CAS  Google Scholar 

  90. Balon R, Petty F, Yergani VK, et al. Intravenous lactate decreases plasma GABA levels in man. Psychopharmacology 1993; 110: 368–70

    Article  PubMed  CAS  Google Scholar 

  91. Wood WD. An attempt to validate the psychoticism scale of the Brief Symptom Inventory. Br J Med Psychol 1982; 55: 367–73

    Article  PubMed  Google Scholar 

  92. Anon. Practical approaches to the treatment of panic disorder. J Clin Psychiatry 1996; 57: 45–52

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  1. Biological Psychiatry Program, Department of Psychiatry, University of Cincinnati College of Medicine and College of Pharmacy, Cincinnati, Ohio, USA

    Jerry A. Bennett, Molly Moioffer, Sean P. Stanton, Megan Dwight & Paul E. Keck Jr

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Bennett, J.A., Moioffer, M., Stanton, S.P. et al. A Risk-Benefit Assessment of Pharmacological Treatments for Panic Disorder. Drug-Safety 18, 419–430 (1998). https://doi.org/10.2165/00002018-199818060-00003

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