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Rapid tryptophan depletion following cognitive behavioural therapy for panic disorder

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Abstract

Objective

The aim of this study was to examine the effect of rapid tryptophan depletion (RTD) combined with a panicogenic challenge in patients with panic disorder who had responded to treatment with cognitive behavioural therapy (CBT). We hypothesised that RTD (compared with the control drink) would result in an increase in anxiety symptoms when provoked by a panicogenic challenge with the benzodiazepine antagonist, flumazenil.

Methods

Nine patients with panic disorder who had responded to CBT received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design. In addition, they received flumazenil and placebo infusions on each day.

Results

Our hypothesis regarding the effects of RTD was supported by findings of a significant interaction between RTD and flumazenil on measures from visual analogues scales (total) and the Spielberger State Anxiety inventory. A somewhat unexpected finding was that in this group of CBT responders, the panicogenic effect of flumazenil was not completely blocked by treatment. This meant that although four of the nine subjects (44%) reported a panicogenic effect of flumazenil on the RTD day, this was not significantly different from the rate of panic attacks in response to flumazenil on the control day.

Conclusion

We suggest that the partial return of symptoms in response to flumazenil reflects a vulnerability to RTD in this group of panic disorder patients who had responded to treatment with CBT.

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References

  • American Psychiatric Association for the Work Group on Panic Disorder (2009) Practice guideline for the treatment of patients with panic disorder (second edition). http://www.psychiatryonline.com/pracGuide/pracGuideTopic_9.aspx

  • Argyropoulos S, Hood SD, Adrover M, Bell CJ, Rich A, Nash JR, Rich NC, Witchel HJ, Nutt DJ (2004) Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder. Biol Psychiatry 56:503–509

    Article  CAS  PubMed  Google Scholar 

  • Barr LC, Goodman WK, McDougle CJ, Delgado PL, Heninger GR, Charney DS, Price LH (1994) Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors. Arch Gen Psychiatry 51:309–317

    CAS  PubMed  Google Scholar 

  • Battaglia M, Perna G (1995) The 35% CO2 challenge in panic disorder: optimization by receiver operating characteristic (ROC) analysis. J Psychiatr Res 29:111–119

    Article  CAS  PubMed  Google Scholar 

  • Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    CAS  PubMed  Google Scholar 

  • Bell C, Forshall S, Adrover M, Nash J, Hood S, Argyropoulos S, Rich A, Nutt DJ (2002) Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine. J Psychopharmacol (Oxf) 16:5–14

    Article  CAS  Google Scholar 

  • Bell CJ, Hood SD, Nutt DJ (2005) Acute tryptophan depletion. Part II: clinical effects and implications. Aust N Z J Psychiatry 39:565–574

    PubMed  Google Scholar 

  • Berney A, Sookman D, Leyton M, Young SN, Benkelfat C (2006) Lack of effects on core obsessive-compulsive symptoms of tryptophan depletion during symptom provocation in remitted obsessive-compulsive disorder patients. Biol Psychiatry 59:853–857

    Article  CAS  PubMed  Google Scholar 

  • Booij L, Van der Does W, Benkelfat C, Bremner JD, Cowen PJ, Fava M, Gillin C, Leyton M, Moore P, Smith KA, Van der Kloot WA (2002) Predictors of mood response to acute tryptophan depletion. A reanalysis. Neuropsychopharmacology 27:852–861

    Article  CAS  PubMed  Google Scholar 

  • Chambless DL, Caputo GC, Bright P, Gallagher R (1984) Assessment of fear of fear in agoraphobics: the body sensations questionnaire and the agoraphobic cognitions questionnaire. J Consult Clin Psychol 52:1090–1097

    Article  CAS  PubMed  Google Scholar 

  • Clark DM (1986) A cognitive approach to panic. Behav Res Ther 24:461–470

    Article  CAS  PubMed  Google Scholar 

  • Clark DM, Salkovskis PM, Hackmann A, Middleton H, Anastasiades P, Gelder M (1994) A comparison of cognitive therapy, applied relaxation and imipramine in the treatment of panic disorder. Br J Psychiatry 164:759–769

    Article  CAS  PubMed  Google Scholar 

  • Corchs F, Nutt DJ, Hood S, Bernik M (2009) Serotonin and sensitivity to trauma-related exposure in selective serotonin reuptake inhibitors-recovered posttraumatic stress disorder. Biol Psychiatry 66:17–24

    Article  CAS  PubMed  Google Scholar 

  • Coupland NJ, Lillywhite A, Bell CE, Potokar JP, Nutt DJ (1997) A pilot controlled study of the effects of flumazenil in posttraumatic stress disorder. Biol Psychiatry 41:988–990

    Article  CAS  PubMed  Google Scholar 

  • Coupland NJ, Bell C, Potokar JP, Dorkins E, Nutt DJ (2000) Flumazenil challenge in social phobia. Depress Anxiety 11:27–30

    Article  CAS  PubMed  Google Scholar 

  • Deakin JF, Graeff FG (1991) 5HT and mechanisms of defence. J Psychopharmacol (Oxf) 5:305–315

    Article  Google Scholar 

  • Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR (1990) Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Archives of General Psychiatry 47:411–418

    CAS  PubMed  Google Scholar 

  • Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, Mayberg H (2004) Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 61:34–41

    Article  PubMed  Google Scholar 

  • Gorman JM, Browne ST, Papp LA, Martinez J, Welkowitz L, Coplan JD, Goetz RR, Kent J, Klein DF (1997) Effect of antipanic treatment on response to carbon dioxide. Biol Psychiatry 42:982–991

    Article  CAS  PubMed  Google Scholar 

  • Gorman JM, Kent JM, Sullivan GM, Coplan JD (2000) Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 157:493–505

    Article  CAS  PubMed  Google Scholar 

  • Guy W (1976) ECDEU Assessment manual for psychopharmacology. US Department of Health, Education, and Welfare, Washington, DC

  • Haynes PL, McQuaid JR, Kelsoe J, Rapaport M, Gillin JC (2004) Affective state and EEG sleep profile in response to rapid tryptophan depletion in recently recovered nonmedicated depressed individuals. J Affect Disord 83:253–262

    Article  CAS  PubMed  Google Scholar 

  • Klein DF (1993) False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry 50:306–317

    CAS  PubMed  Google Scholar 

  • Mavissakalian MR, Perel JM, Talbott-Green M, Sloan C (1998) Gauging the effectiveness of extended imipramine treatment for panic disorder with agoraphobia. Biol Psychiatry 43:848–854

    Article  CAS  PubMed  Google Scholar 

  • McNally RJ, Riemann BC, Kim E (1990) Selective processing of threat cues in panic disorder. Behav Res Ther 28:407–412

    Article  CAS  PubMed  Google Scholar 

  • Miller HE, Deakin JF, Anderson IM (2000) Effect of acute tryptophan depletion on CO2-induced anxiety in patients with panic disorder and normal volunteers. Br J Psychiatry 176:182–188

    Article  CAS  PubMed  Google Scholar 

  • Neumeister A, Hu XZ, Luckenbaugh DA, Schwarz M, Nugent AC, Bonne O, Herscovitch P, Goldman D, Drevets WC, Charney DS (2006) Differential effects of 5-HTTLPR genotypes on the behavioral and neural responses to tryptophan depletion in patients with major depression and controls. Arch Gen Psychiatry 63:978–986

    Article  CAS  PubMed  Google Scholar 

  • Nutt DJ, Glue P, Lawson C, Wilson S (1990) Flumazenil provocation of panic attacks: evidence for altered benzodiazepine receptor sensitivity in panic disorder. Arch Gen Psychiatry 47:917–925

    CAS  PubMed  Google Scholar 

  • O’Reardon JP, Chopra MP, Bergan A, Gallop R, DR J, Crits-Christoph P (2004) Response to tryptophan depletion in major depression treated with either cognitive therapy or selective serotonin reuptake inhibitor antidepressants. Biol Psychiatry 55:957–959

    Article  PubMed  Google Scholar 

  • Perna G, Bertani A, Caldirola D, Gabriele A, Cocchi S, Bellodi L (2002) Antipanic drug modulation of 35% CO2 hyperreactivity and short-term treatment outcome. J Clin Psychopharmacol 22:300–308

    Article  CAS  PubMed  Google Scholar 

  • Prasko J, Horacek J, Zalesky R, Kopecek M, Novak T, Paskova B, Skrdlantova L, Belohlavek O, Hoschl C (2004) The change of regional brain metabolism (18FDG PET) in panic disorder during the treatment with cognitive behavioral therapy or antidepressants. Neuroendocrinol Lett 25:340–348

    PubMed  Google Scholar 

  • Rassovsky Y, Kushner MG, Schwarze NJ, Wangensteen OD (2000) Psychological and physiological predictors of response to carbon dioxide challenge in individuals with panic disorder. J Abnorm Psychology 109:616–623

    Article  CAS  Google Scholar 

  • Sakai Y, Kumano H, Nishikawa M, Sakano Y, Kaiya H, Imabayashi E, Ohnishi T, Matsuda H, Yasuda A, Sato A, Diksic M, Kuboki T (2006) Changes in cerebral glucose utilization in patients with panic disorder treated with cognitive-behavioral therapy. Neuroimage 33:218–226

    Article  PubMed  Google Scholar 

  • Schmidt NB, Trakowski JH, Staab JP (1997) Extinction of panicogenic effects of a 35% CO2 challenge in patients with panic disorder. J Abnorm Psychology 106:630–638

    Article  CAS  Google Scholar 

  • Schruers K, Klaassen T, Pols H, Overbeek T, Deutz NEP, Griez E (2000) Effects of tryptophan depletion on carbon dioxide provoked panic in panic disorder patients. Psychiatry Res 93:179–187

    Article  CAS  PubMed  Google Scholar 

  • Shear MK, Fyer AJ, Ball G, Josephson S, Fitzpatrick M, Gitlin B, Frances A, Gorman J, Liebowitz M, Klein DF (1991) Vulnerability to sodium lactate in panic disorder patients given cognitive-behavioral therapy. Am J Psychiatry 148:795–797

    CAS  PubMed  Google Scholar 

  • Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59:22–33

    PubMed  Google Scholar 

  • Smith KA, Fairburn CG, Cowen PJ (1997) Relapse of depression after rapid depletion of tryptophan. Lancet 349:915–919

    Article  CAS  PubMed  Google Scholar 

  • Spielberger C, Gorsuch R, Lushene R (1970) Manual for the state trait anxiety inventory. Consulting Psychologists Press, Palo Alto

    Google Scholar 

Download references

Acknowledgements

We would like to acknowledge study participants, CBT therapists Ruth Williams and Jo Hurst, Mike Franklin for measurement of plasma tryptophan, David Wilcox and Hannah Slattery who helped with data entry, the Wellcome Trust and Avon and Wiltshire Partnership Trust.

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Authors and Affiliations

  1. University of Otago, Christchurch, New Zealand

    Caroline Bell & Chris Frampton

  2. Psychopharmacology Unit, University of Bristol, Bristol, UK

    John Potokar, Jon Nash, Ann Rich, Spilios Argyropoulos & David Nutt

  3. School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, Australia

    Sean Hood & Dana Hince

  4. Long Stay Unit, Hospital Psiquiatrico (GESMA), Palma de Mallorca, Spain

    Mariona Adrover

  5. Imperial College London, London, UK

    David Nutt

  6. Department of Psychological Medicine, University of Otago, Christchurch, P.O. Box 4345, Christchurch, New Zealand

    Caroline Bell

Authors
  1. Caroline Bell
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  2. Sean Hood
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  3. John Potokar
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  4. Jon Nash
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  7. Dana Hince
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  8. Ann Rich
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  9. Spilios Argyropoulos
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  10. David Nutt
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Correspondence to Caroline Bell.

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Bell, C., Hood, S., Potokar, J. et al. Rapid tryptophan depletion following cognitive behavioural therapy for panic disorder. Psychopharmacology 213, 593–602 (2011). https://doi.org/10.1007/s00213-009-1696-z

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  • DOI: https://doi.org/10.1007/s00213-009-1696-z

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