Background: Nonresponsiveness to therapy is generally acknowledged, but only a few studies have tested switching to psychotherapy. This study is one of the first to examine the malleability of treatment-resistant patients using acceptance and commitment therapy (ACT). Methods: This was a randomized controlled trial that included 43 patients diagnosed with primary panic disorder and/or agoraphobia (PD/A) with prior unsuccessful state-of-the-art treatment (mean number of previous sessions = 42.2). Patients were treated with an ACT manual administered by novice therapists and followed up for 6 months. They were randomized to immediate treatment (n = 33) or a 4-week waiting list (n = 10) with delayed treatment (n = 8). Treatment consisted of eight sessions, implemented twice weekly over 4 weeks. Primary outcomes were measured with the Panic and Agoraphobia Scale (PAS), the Clinical Global Impression (CGI), and the Mobility Inventory (MI). Results: At post-treatment, patients who received ACT reported significantly more improvements on the PAS and CGI (d = 0.72 and 0.89, respectively) than those who were on the waiting list, while improvement on the MI (d = 0.50) was nearly significant. Secondary outcomes were consistent with ACT theory. Follow-up assessments indicated a stable and continued improvement after treatment. The dropout rate was low (9%). Conclusions: Despite a clinically challenging sample and brief treatment administered by novice therapists, patients who received ACT reported significantly greater changes in functioning and symptomatology than those on the waiting list, with medium-to-large effect sizes that were maintained for at least 6 months. These proof-of-principle data suggest that ACT is a viable treatment option for treatment-resistant PD/A patients. Further work on switching to psychotherapy for nonresponders is clearly needed.

Keywords:
Nonresponders, Treatment-resistant patients, Therapy switching, Acceptance and commitment therapy, Panic disorder, Agoraphobia
1.
Barlow DH, Gorman JM, Shear MK, Woods SW: Cognitive-behavioral therapy, imipramine, or their combination for panic disorder - a randomized controlled trial. JAMA 2000;283:2529-2536.
2.
Fava GA, Rafanelli C, Ottolini F, Ruini C, Cazzaro M, Grandi S: Psychological well-being and residual symptoms in remitted patients with panic disorder and agoraphobia. J Affect Disord 2001;65:185-190.
3.
Pollack MH, Otto MW, Roy-Byrne PP, Coplan JD, Rothbaum BO, Simon NM, Gorman JM: Novel treatment approaches for refractory anxiety disorders. Depress Anxiety 2008;25:467-476.
4.
van Balkom AJ, Emmelkamp PM, Eikelenboom M, Hoogendoorn AW, Smit JH, van Oppen P: Cognitive therapy versus fluvoxamine as a second-step treatment in obsessive-compulsive disorder nonresponsive to first-step behavior therapy. Psychother Psychosom 2012;81:366-374.
5.
Palatnik A, Frolov K, Fux M, Benjamin J: Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. J Clin Psychopharm 2001;21:335-339.
6.
Rodrigues H, Figueira I, Goncalves R, Mendlowicz M, Macedo T, Ventura P: CBT for pharmacotherapy non-remitters - a systematic review of a next-step strategy. J Affect Disord 2011;129:219-228.
7.
Fava GA, Savron G, Zielezny M, Grandi S, Rafanelli C, Conti S: Overcoming resistance to exposure in panic disorder with agoraphobia. Acta Psychiatr Scand 1997;95:306-312.
8.
White KS, Payne LA, Gorman JM, Shear MK, Woods SW, Saksa JR, Barlow DH: Does maintenance CBT contribute to long-term treatment response of panic disorder with or without agoraphobia? A randomized controlled clinical trial. J Consult Clin Psychol 2013;81:47-57.
9.
Kazdin AE: Mediators and mechanisms of change in psychotherapy research. Annu Rev Clin Psychol 2007;3:1-27.
10.
Fava GA, Tomba E, Tossani E: Innovative trends in the design of therapeutic trials in psychopharmacology and psychotherapy. Prog Neuropsychopharmacol Biol Psychiatry 2013;40:306-311.
11.
Gloster AT, Wittchen HU, Einsle F, Lang T, Helbig-Lang S, Fydrich T, Fehm L, Hamm AO, Richter J, Alpers GW, Gerlach AL, Strohle A, Kircher T, Deckert J, Zwanzger P, Hofler M, Arolt V: Psychological treatment for panic disorder with agoraphobia: a randomized controlled trial to examine the role of therapist-guided exposure in situ in CBT. J Consult Clin Psychol 2011;79:406-420.
12.
Gloster AT, Klotsche J, Wittchen HU, Helbig-Lang S, Lang T, Gerlach AL, Richter J, Alpers GW, Fehm L, Kircher T, Hamm AO, Ströhle A, Deckert J: Timing matters: mediators of outcomes in cognitive behavioral therapy for panic disorder with agoraphobia depend on the stage of treatment. J Consult Clin Psychol, in press.
13.
Deacon B, Kemp JJ, Dixon LJ, Sy JT, Farrell NR, Zhang AR: Maximizing the efficacy of interoceptive exposure by optimizing inhibitory learning: a randomized controlled trial. Behav Res Ther 2013;51:588-596.
14.
Fava GA, Ruini C, Rafanelli C: Sequential treatment of mood and anxiety disorders. J Clin Psychiatry 2005;66:1392-1400.
15.
Fava GA, Fabbri S, Sonino N: Residual symptoms in depression: an emerging therapeutic target. Prog Neuropsychopharmacol Biol Psychiatry 2002;26:1019-1027.
16.
Hayes SC, Strosahl KD, Wilson KG: Acceptance and Commitment Therapy, ed 2. New York, Guilford Press, 2012.
17.
Hayes SC, Luoma JB, Bond FW, Masuda A, Lillis J: Acceptance and commitment therapy: model, processes and outcomes. Behav Res Ther 2006;44:1-25.
18.
Dalrymple KL, Herbert JD: Acceptance and commitment therapy for generalized social anxiety disorder - a pilot study. Behav Modif 2007;31:543-568.
19.
Eifert GH, Forsyth JP, Arch J, Espejo E, Keller M, Langer D: Acceptance and commitment therapy for anxiety disorders: three case studies exemplifying a unified treatment protocol. Cogn Behav Pract 2009;16:368-385.
20.
Arch JJ, Eifert GH, Davies C, Plumb Vilardaga JC, Rose RD, Craske MG: Randomized clinical trial of cognitive behavioral therapy (CBT) versus acceptance and commitment therapy (ACT) for mixed anxiety disorders. J Consult Clin Psychol 2012;80:750-765.
21.
Chambless DL, Caputo GC, Jasin SE, Gracely EJ, Williams C: The mobility inventory for agoraphobia. Behav Res Ther 1985;23:35-44.
22.
Shear MK, Vander Bilt J, Rucci P, Endicott J, Lydiard B, Otto MW, Pollack MH, Chandler L, Williams J, Ali A, Frank DM: Reliability and validity of a structured interview guide for the Hamilton Anxiety Rating Scale (SIGH-A). Depress Anxiety 2001;13:166-178.
23.
Bandelow B, Zohar J, Hollander E, Kasper S, Moller HJ, Allgulander C, Ayuso-Gutierrez J, Baldwin D, Bunevicius R, Cassano G, Fineberg N, Gabriels L, Hindmarch I, Kaiya H, Klein DF, Lader M, Lecrubier Y, Lepine JP, Liebowitz MR, Lopez-Ibor JJ, Marazziti D, Miguel EC, Oh KS, Preter M, Rupprecht R, Sato M, Starcevic V, Stein DJ, van Ameringen M, Vega J; WFSBP Task Force on Treatment Guidelines for Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders: World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision. World J Biol Psychiatry 2008;9:248-312.
24.
Arzneimittelkommission der deutschen Ärzteschaft: Empfehlungen zur Therapie von Angst- und Zwangsstörungen. Arzneiverordnung in der Praxis 2003;30:(suppl 4):1-22.
25.
Eifert GH, Forsyth JP: Acceptance and Commitment therapy for Anxiety Disorders: A Practitioner's Treatment Guide to Using Mindfulness, Acceptance, and Values-Based Behavior Change Strategies. Oakland, New Harbinger Publications, 2005.
26.
Gloster AT, Klotsche J, Chaker S, Hummel KV, Hoyer J: Assessing psychological flexibility: what does it add above and beyond existing constructs? Psychol Assess 2011;23:970-982.
27.
Gloster AT, Hummel KV, Lyudmirskaya I, Hauke C, Sonntag RF: Exposure Therapy: Rethinking the Model - Refining the Method. New York, Springer Science + Business Media, 2012, pp 127-152.
28.
McGrath KB: Validation of the Drexel University ACT/tCBT Adherence and Competence Rating Scale: Revised for Use in a Clinical Population. Philadelphia, Drexel University, 2012.
29.
Bandelow B: Panik- und Agoraphobieskala (PAS). Göttingen, Hogrefe, 1997.
30.
Bandelow B: Assessing the efficacy of treatments for panic disorder and agoraphobia. II. The Panic and Agoraphobia Scale. Int Clin Psychopharmacol 1995;10:73-81.
31.
Guy W: ECDEU Assessment Manual for Psychopharmacology. Rockville, Department of Health, Education, and Welfare, 1976.
32.
Chambless DL, Caputo GC, Jasin SE, Gracely EJ, Williams C: The mobility inventory for agoraphobia. Behav Res Ther 1985;23:35-44.
33.
Essau CA, Wittchen HU: An overview of the Composite International Diagnostic Interview (CIDI). Int J Methods Psychiatr Res 1993;3:79-85.
34.
Lachner G, Wittchen HU, Perkonigg A, Holly A, Schuster P, Wunderlich U, Turk D, Garczynski E, Pfister H: Structure, content and reliability of the Munich Composite International Diagnostic Interview (M-CIDI) substance use sections. Eur Addict Res 1998;4:28-41.
35.
Reed V, Gander F, Pfister H, Steiger A, Sonntag H, Trenkwalder C, Sonntag A, Hundt W, Wittchen HU: To what degree does the Composite International Diagnostic Interview (CIDI) correctly identify DSM-IV disorders? Testing validity issues in a clinical sample. Int J Methods Psychiatr Res 1998;7:142-155.
36.
Robins LN, Wing J, Wittchen HU, Helzer JE, Babor TF, Burke J, Farmer A, Jablenski A, Pickens R, Regier DA, Sartorius N, Towle LH: The composite international diagnostic interview - an epidemiologic instrument suitable for use in conjunction with different diagnostic systems and in different cultures. Arch Gen Psychiatry 1988;45:1069-1077.
37.
Wittchen HU: Reliability and validity studies of the WHO - Composite International Diagnostic Interview (CIDI) - a critical review. J Psychiatr Res 1994;28:57-84.
38.
Wittchen HU, Pfister H: Instruktionsmanual zur Durchführung von Dia-X Interviews. Frankfurt, Swets and Zeitlinger, 1997.
39.
Chambless DL, Caputo GC, Bright P, Gallagher R: Assessment of fear of fear in agoraphobics - the body sensations questionnaire and the agoraphobic cognitions questionnaire. J Consult Clin Psychol 1984;52:1090-1097.
40.
Reiss S, Peterson RA, Gursky DM, McNally RJ: Anxiety sensitivity, anxiety frequency and the prediction of fearfulness. Behav Res Ther 1986;24:1-8.
41.
Beck AT, Steer RA, Brown GK: BDI-II, Beck Depression Inventory: Manual. San Antonio, Psychological Corporation, 1996.
42.
Beck AT, Steer RA: Manual for the Beck Anxiety Inventory. San Antonio, Psychological Corporation, 1990.
43.
Gratz KL, Roemer L: Multidimensional assessment of emotion regulation and dysregulation: development, factor structure, and initial validation of the difficulties in emotion regulation scale. J Psychopathol Behav 2004;26:41-54.
44.
Wegner DM, Zanakos S: Chronic thought suppression. J Pers 1994;62:615-640.
45.
Baer RA, Smith GT, Allen KB: Assessment of mindfulness by self-report - the Kentucky inventory of mindfulness skills. Assessment 2004;11:191-206.
46.
Herzberg KN, Sheppard SC, Forsyth JP, Crede M, Earleywine M, Eifert GH: The Believability of Anxious Feelings and Thoughts Questionnaire (BAFT): a psychometric evaluation of cognitive fusion in a nonclinical and highly anxious community sample. Psychol Assess 2012;24:877-891.
47.
van Buuren S, Groothuis-Oudshoorn K: MICE: Multivariate imputation by chained equations in R. J Stat Softw 2011;45:1-67.
48.
Pinheiro J, Bates D: Mixed-Effects Models in S and S-Plus. New York, Springer, 2002.
49.
Gloster AT, Hauke C, Hofler M, Einsle F, Fydrich T, Hamm A, Sthrohle A, Wittchen HU: Long-term stability of cognitive behavioral therapy effects for panic disorder with agoraphobia: a two-year follow-up study. Behav Res Ther 2013;51:830-839.
50.
Durham RC, Higgins C, Chambers JA, Swan JS, Dow MGT: Long-term outcome of eight clinical trials of CBT for anxiety disorders: symptom profile of sustained recovery and treatment-resistant groups. J Affect Disord 2012;136:875-881.
51.
Schlaepfer TE, Agren H, Monteleone P, Gasto C, Pitchot W, Rouillon F, Nutt DJ, Kasper S: The hidden third: improving outcome in treatment-resistant depression. J Psychopharmacol 2012;26:587-602.
52.
Arch JJ, Ayers CR: Which treatment worked better for whom? Moderators of group cognitive behavioral therapy versus adapted mindfulness based stress reduction for anxiety disorders. Behav Res Ther 2013;51:434-442.
53.
Kenny MA, Williams JMG: Treatment-resistant depressed patients show a good response to mindfulness-based cognitive therapy. Behav Res Ther 2007;45:617-625.
54.
Fava GA: Well-being therapy: conceptual and technical issues. Psychother Psychosom 1999;68:171-179.
55.
Hofmann SG, Smits JAJ: Cognitive-behavioral therapy for adult anxiety disorders: a meta-analysis of randomized placebo-controlled trials. J Clin Psychiatry 2008;69:621-632.
56.
Gould RA, Otto MW, Pollack MH: A meta-analysis of treatment outcome for panic disorder. Clin Psychol Rev 1995;15:819-844.
57.
Taylor S, Abramowitz JS, McKay D: Non-adherence and non-response in the treatment of anxiety disorders. J Anxiety Disord 2012;26:583-589.
58.
Taylor S, Abramowitz JS, McKay D: Non-adherence and non-response in the treatment of anxiety disorders. J Anxiety Disord 2012;26:583-589.
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