Elsevier

Comprehensive Psychiatry

Volume 48, Issue 5, September–October 2007, Pages 419-425
Comprehensive Psychiatry

Three-year medication prophylaxis in panic disorder: to continue or discontinue? A naturalistic study

https://doi.org/10.1016/j.comppsych.2007.04.003Get rights and content

Abstract

Objective

Little is known about maintenance treatment for panic disorder. The purpose of this naturalistic study is to compare outcomes of remitted panic disorder patients continued on versus those successfully discontinued from maintenance medication.

Methods

After 3 years of sustained remission with medication in a naturalistic setting, 168 patients were continued on, whereas 37 successfully discontinued from medication. Continued and discontinued groups were followed for an additional 4 to 8 years and compared for differences in treatment outcome using χ2 and Wilcoxon rank sum tests. Times to relapse were analyzed using the Kaplan-Meier product-limit method, and risk factors for relapse were assessed using Cox proportional hazards regression.

Results

The discontinued group was healthier at baseline but had a significantly worse outcome compared with the continued group. Panic-free survival probabilities for the continued group at 1, 2, 3, and 4 years were 0.87, 0.81, 0.71, and 0.64, respectively, and were significantly higher than respective probabilities of 0.53, 0.35, 0.29, and 0.15 for the discontinued group. Median survival time in the continued group was significantly longer, at 5.67 years, than in the discontinued group, at 1.17 years. Cognitive behavioral therapy significantly reduced hazard in the discontinued but not in the continued group. Residual symptoms in either group at time of assignment predicted poorer outcome.

Conclusion

Our small study suggests that relapse of panic disorder in routine clinical practice occurs even after long-standing remission on maintenance medication, and that relapse risk appears to be markedly higher after medication discontinuation. Discontinuation may be more successful in candidates who received cognitive behavioral therapy and have minimal residual symptoms.

Introduction

Panic disorder is a common psychiatric illness with a lifetime prevalence of 4.7% in the United States [1]. It is characterized by a chronic, fluctuant course and is highly comorbid with other psychiatric disorders, including substance abuse and dependence [2], mood disorders [3], [4], other anxiety disorders [5], and personality disorders [6]. Panic disorder is increasingly recognized as a major mental health problem with a high degree of functional impairment [7], [8], [9], poor quality of life [10], [11], [12], and increased risk of suicide [13], [14], [15].

Panic disorder responds well to tricyclic antidepressants (TCAs), serotonin-reuptake inhibitors, or combination treatment with benzodiazepines [16]. After successful treatment, how long do patients need to remain on medication? The American Psychiatric Association (APA) practice guideline recommends at least 1 year of maintenance after 12 weeks of acute stabilization [16], but this recommendation is based on limited empirical data. Controlled discontinuation studies have found a wide range of relapse rates, from 30% with sertraline [17] to more than 70% with alprazolam [18]. Patients from these studies may not be representative of individuals in the community because they were participants in a research treatment protocol before the discontinuation phrase. Available naturalistic studies have generally used retrospective data obtained from a one-time follow-up visit many years after the acute treatment period [19], limiting their ability to characterize treatment course over time. In this context, the optimal duration of maintenance therapy after acute stabilization remains unclear.

The purpose of this study was to compare the treatment outcome of patients who were continued on versus those successfully discontinued from medication after 3 years of panic-free remission. Although previous studies have noted a lower survival probability in patients who discontinued medication [17], [20], we did not expect any difference in survival probabilities in our patients because we hypothesized that 3 years of maintenance treatment—a period that is significantly longer than that of previous studies—would be sufficient prophylaxis against relapse. To our knowledge, this is the only naturalistic, longitudinal study to date in which medication discontinuation was systematically attempted after 3 years of maintenance treatment, and patients were followed for an additional 4 to 8 years in clinical practice.

Section snippets

Study patients

Patients (N = 217) in the study were receiving routine clinical care at Freedom from Fear. Freedom from Fear (Staten Island, NY) is a mental illness advocacy organization and an urban community clinic that specializes in the treatment of anxiety disorders. Patients met Diagnostic and Statistical Manual of Mental Disorders, Third Edition, (DSM-III) diagnosis of panic disorder with or without agoraphobia. Diagnosis was determined by consensus from 2 clinicians as part of routine assessment during

Assignment, demographics, baseline symptoms, and treatment profiles

Of the 217 participants, 168 choose to remain on medication (the continued group), 37 successfully completed medication taper (the discontinued group), and 12 failed to discontinue medication because of severe anxiety during the taper period. A total of 30 patients were lost to follow-up (14.6%): 2 from the discontinued group and 28 from the continued group. These patients were included in the analysis and categorized as terminated well based on their last visit.

There was no significant

Discussion

The main finding in our study was that patients who successfully discontinued from medication had a poorer treatment outcome compared with those who remained on medication. The median survival time of patients who discontinued medication was only one fifth of that enjoyed by patients continued on medication, and their risk of relapse was significantly higher at 4 years follow-up (85% vs 36%). Although these results were unexpected as we had hoped that 3 years of maintenance treatment would be

Acknowledgments

The authors thank Freedom from Fear, a mental illness advocacy organization for their support with this project. Many thanks to the staff at the Freedom from Fear for their assistance in the administrative aspects of the study. We also greatly appreciate the following physicians for their help in data collection: Sunil Khushalani, MD; Wieslawa Tomaszewska, MD; Michael Z. Sobel, MD; Alexandria Hallin, MD; R. Sandlin Lowe, MD; R. Todd Lafargue MD; Gita Vaid, MD. We are very grateful to Carole

References (41)

  • R.C. Kessler

    The prevalence of psychiatric morbidity

  • M.B. Keller et al.

    Remission and relapse in subjects with panic disorder and panic with agoraphobia: a prospective short-interval naturalistic follow-up

    J Nerv Ment Dis

    (1994)
  • M.H. Pollack et al.

    Longitudinal course of panic disorder: findings from the Massachusetts General Hospital Naturalistic Study

    J Clin Psychiatry

    (1990)
  • J.S. Markowitz et al.

    Quality of life in panic disorder

    Arch Gen Psychiatry

    (1989)
  • M. Mogotsi et al.

    Quality of life in the anxiety disorders

    Harv Rev Psychiatry

    (2000)
  • P.J. Candilis et al.

    Quality of life in patients with panic disorder

    J Nerv Ment Dis

    (1999)
  • W. Coryell et al.

    Excess mortality in panic disorder. A comparison with primary unipolar depression

    Arch Gen Psychiatry

    (1982)
  • M.M. Weissman et al.

    Suicidal ideation and suicide attempts in panic disorder and attacks

    N Engl J Med

    (1989)
  • J. Gorman et al.

    Practice guideline for the treatment of patients with panic disorder

  • M.H. Rapaport et al.

    Sertraline treatment of panic disorder: results of a long-term study

    Acta Psychiatr Scand

    (2001)
  • Cited by (0)

    This study was not supported by any outside grant or sponsored by any pharmaceutical companies. Study was completed at the Freedom from Fear, 308 Seaview Avenue, Staten Island, NY 10305.

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