Elsevier

Biological Psychiatry

Volume 44, Issue 5, 1 September 1998, Pages 348-360
Biological Psychiatry

Review Articles
Implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression

https://doi.org/10.1016/S0006-3223(98)00110-3Get rights and content

Abstract

This is a review article that describes current data, issues, and controversies regarding long-term maintenance treatment of depression. The authors suggest that the issues represent a public health crisis. This paper will identify the need, from both a health-care and economic perspective, for more research on the efficacy of maintenance treatment for this pernicious and lifelong disorder. Data will be reviewed on the natural course of unipolar depression, focusing on clinical predictors that increase the risk of a relapse or recurrence. This review will include new data from the National Institute of Mental Health Collaborative Depression Study. Failing to achieve adequate maintenance treatment for unipolar recurrent major depression has psychopathological and psychosocial consequences, decreasing work productivity and the quality of a person’s life. Published double-blind placebo-controlled studies on continuation treatment of major depression will be reviewed. The two competed double-blind placebo-controlled long-term maintenance studies of recurrent unipolar major depression will be discussed in detail. Despite the positive findings from research done to date, there remain many unresolved questions relating to the maintenance treatment of recurrent unipolar major depression, and the need for research in this area is critical. The paper concludes with recommendations for long-term maintenance treatment of unipolar major depression.

Introduction

This article focuses on the implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression. The background will start with a brief review of data on the natural course of unipolar major depression. This review will then include a discussion of several topics: the epidemiology of unipolar major depression; the cumulative probability of time to recovery, including episode duration and likelihood of chronicity; and specification of clinical predictors that increase the risk of a relapse/recurrence after recovery from unipolar major depression. Data will be presented on associated comorbidity, including comparison with data from other chronic and recurrent medical illnesses, and morbidity and mortality from suicide.

Published data will be presented, and recently analyzed findings from the National Institute of Mental Health (NIMH) Collaborative Depression Study (CDS) that have not yet been accepted for publication will be discussed. This paper will also briefly review data on the probability of patients with unipolar major depression to receive the correct treatment in sufficient duration and dosage. The purpose of this review is to quantify the importance of this public health crisis. Furthermore, this review will identify the need, from both a healthcare and economic perspective, to show the efficacy of maintenance treatment for this pernicious and lifelong disorder.

Data from patients in the CDS, and findings from Angst’s long-term prospective study of mood disorders (Angst 1986), will be used to show the consequences of failing to achieve adequate maintenance treatment for unipolar recurrent major depression. Such a failure can have not only psychopathological, but also psychosocial consequences, decreasing work productivity and the quality of a person’s life. The lack of a control group in this study places important caveats on interpreting the data; however, it does give many insights into the natural course in the largest cohort of people whose depression led them to seek inpatient and outpatient treatment in university-based medical centers, and who were then followed up prospectively at short intervals. This cohort has been systematically and comprehensively assessed, at least annually, for a minimum of 18 years. Recent NIMH funding will extend the follow-up to at least 23 years on all subjects.

This paper will then identify and examine the current unresolved questions relating to the maintenance treatment of recurrent unipolar major depression. In doing so, this paper will analyze published data, presented in peer-reviewed journals, on randomized controlled clinical trials of continuation and maintenance studies of recurrent unipolar major depression.

Section snippets

Epidemiology of major depression

The most recent epidemiologic study estimates the lifetime prevalence rate of major depression in the United States at 17.1%, and the rate of unipolar major depression at approximately 16% (Kessler et al 1994). This is consistent with several other epidemiologic studies conducted in different regions of the world since 1988 Weissman et al 1992, Hwu et al 1989.

Morbidity and mortality from unipolar major depression

Available data show that the morbidity and mortality from major depressive disorder and major depressive symptoms are comparable to that

Duration of treatment

What duration of treatment is appropriate for recurrent unipolar major depression? Possible durations include the following: 1) 6 months, the conventional duration of the continuation phase; 2) 1 year, a length supported by at least three continuation studies; 3) 2 years, which is supported by two treatment studies; and 4) 5 years, the duration of one treatment study (Kupfer et al 1992). The 5-year study randomized 20 subjects to active treatment or placebo after they had been maintained in a

Summary

This paper attempts to: 1) present the state of knowledge about long-term treatment of recurrent unipolar major depression; 2) stress the crucial need for continued research in this area; and 3) specify the opportunities for antidepressants that display long-term maintenance efficacy. To answer the unresolved questions presented in this paper, a study would be required with an adequate sample size needed (600–800 subjects) and a reasonable duration of maintenance treatment (3–5 years).

Acknowledgements

The authors acknowledge the invaluable assistance of Ms. Laura Hitt, MA, in the preparation of the manuscript, including literature review and editing of the text.

This work was presented at the Neuroscience Discussion Forum “A Decade of Serotonin Research” held at Amelia Island, Florida in November 1997. The conference was sponsored by the Society of Biological Psychiatry through an unrestricted educational grant provided by Eli Lilly and Company.

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