Diagnostic conversion from depression to bipolar disorders: results of a long-term prospective study of hospital admissions

Abstract

Objectives: To analyse the time course and some risk factors for a diagnostic change from major depression to bipolar disorders (BP) over an average of 20 years from the onset of the disorders. Methods: Patients (406) with major mood disorders hospitalised at some time between 1959 and 1963 were followed-up until 1985. The analysis also included the course prior to hospitalisation. Survival analyses and Cox regression models were applied. Results: A diagnostic change from depression to bipolar I occurred in about 1% of the patients per year and to bipolar II disorders in about 0.5% per year. Risk factors for a change from depression to BP-I disorder were male sex and an early onset of the disorder; risk factors for a change from depression to BP-II disorder were female sex, a later onset of the disorder and a positive family history of mania. Conclusions: Across the entire lifetime, every new episode of depression brings a new risk for mania; more than half of our severe mood disorder cases became bipolars. The risk of depression developing into bipolar disorder remains constant lifelong. Limitations: The diagnostic classification of ICD-9 met RDC criteria for bipolar disorder in only 90% of cases. Part of the data collected in retrospect may be less reliable; the prospective data were only collected every 5 years from 1965 to 1985 using multiple sources; mild manifestations between the follow-ups may have been partially missed. The sample of subsequent hospital admissions for major depression and mania represents a severe group of patients and generalisations to ambulatory cases may not be possible. Not all risk factors for diagnostic conversion described in the literature could be assessed in this study.

Introduction

The homogeneity and unity of manic-depressive disorders (Kraepelin, 1898) were disproved in the late 1960s by three monographs Angst, 1966, Perris, 1966, Winokur et al., 1969 and the distinction between bipolar disorder (BP) (Falret, 1851) and depression was re-introduced. Since then, a persistent problem has been the uncertain diagnosis of depressive disorder, since it is clear that the group of recurrent depressives includes hidden bipolar subjects whose depression may develop into hypomania or mania at any time. One consequence of this is the long time elapsing between the onset of depression and a diagnosis of BP. This period was more than 7.5 years in the retrospective study of Ghaemi et al. (1999) and 8 years in a national survey of the NDMDA (1993) in the United States. Underdiagnosis of minor bipolar syndromes is the rule.

Although there have been many reports on the rates of diagnostic changes from depression to bipolar disorder (reviewed by Angst, 1988), few of them have taken the length of follow-up into account. On the basis of four large studies Kinkelin, 1954, Marneros et al., 1991, Coryell et al., 1995, Angst and Preisig, 1995a, we estimated a mean diagnostic change rate of 1% per year of observation (Angst, 2000). Coryell et al. (1995), for instance, found 5.0% diagnostic changes from depression to hypomania and 5.2% to mania over 10 years of follow-up; 7.5% of bipolar II patients developed mania.

The rates recently reported by Goldberg et al. (2001) in a 15-year follow-up of 74 initially hospitalised patients were higher, with the diagnosis changing from depression to hypomania in 26% and from depression to mania in 19% of patients. Their survival analyses suggested a constant (linear) risk of diagnostic change.

This paper will not deal with the risk of depressive episodes switching into hypomania or mania, and will therefore not discuss the hypothesis that antidepressants are risk factors for such a switch (Goodwin and Jamison, 1990). Nor will it analyse the time-point of such switches within a depressive episode.

The goal of this paper is to specifically describe the risks of long-term diagnostic conversion from depression to bipolar disorder (bipolar I and bipolar II) as a function of time, and in relation to age of onset, number of depressive episodes, sex and family history for bipolar disorder. In contrast to earlier analyses of the course (Angst and Preisig, 1995a), this paper applies survival techniques for the description of the time course of diagnostic changes over lifetime, including 26 years of prospective follow-up.