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Original Research

A Randomized Trial of Cognitive-Behavioral Therapy or Selective Serotonin Reuptake Inhibitor or Both Combined for Panic Disorder With or Without Agoraphobia: Treatment Results Through 1-Year Follow-Up

Franske J. van Apeldoorn, MSc; Marieke E. Timmerman, PhD; Peter Paul A. Mersch, PhD; Wiljo J. P. J. van Hout, PhD; Sako Visser, PhD; Richard van Dyck, MD, PhD; and Johan A. den Boer, MD, PhD

Published: May 15, 2010

Article Abstract

Objective: To establish the long-term effectiveness of 3 treatments for DSM-IV panic disorder with or without agoraphobia: cognitive-behavioral therapy (CBT), pharmacotherapy using a selective serotonin reuptake inhibitor (SSRI), or the combination of both (CBT + SSRI). As a secondary objective, the relationship between treatment outcome and 7 predictor variables was investigated.

Method: Patients were enrolled between April 2001 and September 2003 and were randomly assigned to treatment. Academic and nonacademic clinical sites participated. Each treatment modality lasted 1 year. Pharmacotherapists were free to choose between 5 SSRIs currently marketed in The Netherlands. Outcome was assessed after 9 months of treatment (posttest 1), after discontinuation of treatment (posttest 2), and 6 and 12 months after treatment discontinuation (follow-up 1 and follow-up 2).

Results: In the sample (N = 150), 48% did not suffer from agoraphobia or suffered from only mild agoraphobia, while 52% suffered from moderate or severe agoraphobia. Patients in each treatment group improved significantly from pretest to posttest 1 on the primary outcome measures of level of anxiety (P < .001), degree of coping (P < .001), and remitter status (P < .001), as well as on the secondary outcome measures of depressive symptomatology (P < .001), and from pretest to posttest 2 for health-related quality of life (P < .001). Gains were preserved from posttest 2 throughout the follow-up period. Some superiority of CBT + SSRI and SSRI as compared with CBT was observed at posttest 1. However, at both follow-ups, differences between treatment modalities proved nonsignificant. Client satisfaction appeared to be high at treatment endpoint, while patients receiving CBT + SSRI appeared slightly (P < .05) more satisfied than those receiving CBT only.

Conclusions: No fall-off in gains was observed for either treatment modality after treatment discontinuation. SSRIs were associated with adverse events. Gains produced by CBT were slower to emerge than those produced by CBT + SSRI and SSRI, but CBT ended sooner.

Trial Registration: Netherlands Trial Register ( Identifier: ISRCTN8156869

J Clin Psychiatry 2010;71(5):574-586

Submitted: September 5, 2008; accepted April 20, 2009.

Corresponding author: Franske J. van Apeldoorn, MSc, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands (

Volume: 71

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