Gauging the Effectiveness of Extended Imipramine Treatment for Panic Disorder with Agoraphobia

doi:10.1016/S0006-3223(97)00376-4

Biological Psychiatry

Volume 43, Issue 11, 1 June 1998, Pages 848-854

https://doi.org/10.1016/S0006-3223(97)00376-4 Get rights and content

Abstract

Background: Imipramine has proven efficacy for panic disorder. This study assesses the net effectiveness of systematic, open imipramine treatment in a homogenous sample of panic disorder patients with agoraphobia.

Methods: One hundred and ten consecutive patients with DSM-III-R moderate to severe panic disorder with agoraphobia were treated with a fixed regimen of imipramine 2.25 mg/kg/day for 24 weeks. No instructions or encouragement for self-directed exposure to phobic situations or other coping strategies with panic or fear were given. Assessments were conducted at the end of the 2-week placebo run-in and at weeks 8, 16, and 24 of treatment.

Results: Overall, 53% had a marked and stable response. Most measures revealed that substantial improvement continued beyond week 8 of treatment. Treatment success was accompanied with significant improvements in anxiety sensitivity, dysphoric mood, and functional well-being.

Conclusions: These results provide a clinically relevant reference with which to compare the effectiveness of alternative treatments in providing nearly complete symptom remission in patients with primary panic disorder with agoraphobia.

Introduction

Imipramine is the most extensively studied pharmacologic treatment of panic disorder. Large placebo controlled studies (Cross-National Collaborative Panic Study, Second Phase Investigators 1992) have firmly established the efficacy of imipramine in panic disorder in general and panic disorder with agoraphobia in particular (Maier et al 1991). A recent dose-ranging study (Mavissakalian and Perel 1995) in panic disorder with agoraphobia has provided incontrovertible evidence for imipramine’s specific antipanic and antiphobic effects in this more fully developed and usually more severe syndromal form of the disorder. Further evidence suggests that imipramine’s effects become consolidated over 6 months of treatment Zitrin et al 1980, Telch et al 1985, Clark et al 1994, Schweizer et al 1993 and that continued treatment maintains treatment gains over extended periods of time (Mavissakalian and Perel 1992).

The aim of the present paper was to determine the net effectiveness of systematic, open imipramine treatment in panic disorder with agoraphobia patients and to characterize the 6-month treatment outcome in salient symptom and quality of life domains. Because this protocol aimed to transfer optimal pharmacologic treatment in terms of dosing and duration into this large sample, the present results provide a useful reference with which to gauge the effectiveness of newer, primarily nonbenzodiazepine, pharmacologic agents in panic disorder with agoraphobia.

Section snippets

Subjects

Subjects included the first 110 consecutive patients with a diagnosis of panic disorder with agoraphobia who gave informed consent and who started the active open imipramine treatment planned for 24-weeks overall. This protocol preceded an ongoing placebo-controlled, 12-month maintenance phase trial. Subjects, aged 18–65 years, contacted the Phobia and Anxiety Disorders Clinic either through clinical referrals or in response to media coverage or advertisement. In addition to meeting DSM-III-R

Net effectiveness of treatment

Of the 110 patients started on imipramine, 77 completed week 8, 66 completed week 16, and 59 went on to week 24 in stable remission, yielding a net effectiveness of 53%. Table 1 presents the proportion of patients meeting three categories of response based on the ESF scale at weeks 8, 16, and 24 of treatment, respectively. Three analyses of interest were applied to these data. First, Bowker’s test of symmetry showed that between weeks 8 and 16 responder status was more likely to improve than to

Discussion

With the advent of newer antidepressants (Preskorn 1994) that share common active mechanisms with imipramine and have more favorable side effect profiles, treatment selection may shift from efficacy-based considerations to practical emphasis on effectiveness (i.e., the likelihood that patients started on a given treatment can take it without adversity and have a successful outcome). This study indicates a net effectiveness of 53% for imipramine in the treatment of panic disorder with

Acknowledgements

Supported by National Institute of Mental Health Grant MH42730 and National Institute of Mental Health Clinical Research Center Grant MH30915. We acknowledge the assistance of Michael Fligner, Ph.D., for the statistical analysis and of Nicholas Votolato, R.Ph., in pharmacy support, and Cross-National Collaborative Panic Study, Second Phase Investigators of Dev Pathak, Ph.D., for his helpful suggestions regarding the pharmacoeconomic assessments.

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Original ArticlesGauging the Effectiveness of Extended Imipramine Treatment for Panic Disorder with Agoraphobia

Abstract

Introduction

Section snippets

Subjects

Net effectiveness of treatment

Discussion

Acknowledgements

J Chromatogr

J Behav Ther Exp Psychiatry

Behav Res Ther

Behav Res Ther

J Chromatogr

Diagnostic and Statistical Manual of Mental Disorders

An inventory for measuring depression

Arch Gen Psychiatry

A comparison of cognitive therapy, applied relaxation and imipramine in the treatment of panic disorder

Br J Psychiatry

Drug treatment of panic disorderComparative efficacy of alprazolam, imipramine, and placebo