Research report
Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP)

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Abstract

Background: This paper presents the methodology and clinical data in mid-stream from a French multi-center study (EPIDEP) in progress on a national sample of patients with DSM-IV major depressive episode (MDE). The aim of EPIDEP is to show the feasibility of validating the spectrum of soft bipolar disorders by practising clinicians. In this report, we focus on bipolar II (BP-II). Method: EPIDEP involves training 48 French psychiatrists in 15 sites; construction of a common protocol based on the criteria of DSM-IV and Akiskal (Soft Bipolarity), as well as criteria modified from the work of Angst (Hypomania Checklist), the Ahearn-Carroll Bipolarity Scale, HAM-D and Rosenthal Atypical Depression Scale; Semi-Structured Interview for Evaluation of Affective Temperaments (based on Akiskal-Mallya), self-rated Cyclothymia Scale (Akiskal), family history (Research Diagnostic Criteria); and prospective follow-up. Results: Results are presented on 250 (of the 537) MDE patients studied thus far during the acute phase. The rate of BP-II disorder which was 22% at initial evaluation, nearly doubled (40%) by systematic evaluation. As expected from the selection of MDE by uniform criteria, inter-group comparison between BP-II vs unipolar showed no differences on the majority of socio-demographic parameters, clinical presentation and global intensity of depression. Despite such uniformity, key characteristics significantly differentiated BP-II from unipolar: younger age at onset of first depression, higher frequency of suicidal thoughts and hypersomnia during index episode, higher scores on Hypomania Checklist and cyclothymic and irritable temperaments, and higher switching rate under current treatment. Eighty-eight percent of cases assigned to cyclothymic temperament by clinicians (with a cut-off of 10/21 items on self-rated cyclothymia) were recognized as BP-II. Evaluation of this temperament by clinician and patient correlated at a highly significant level (r=0.73; p<0.0001). Cyclothymia and hypomania were also correlated significantly (r=0.51; p<0.001). Limitation: In a study conducted in diverse clinical settings, it was not possible to assure that clinicians making affective diagnoses were blind to the various temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. Conclusion: With a systematic search for hypomania, 40% of major depressive episodes were classified as BP-II, of which only half were known to the clinicians at study entry. Cyclothymic temperamental dysregulation emerged as a robust clinical marker of BP-II disorder. These data indicate that clinicians in diverse practice settings can be trained to recognize soft bipolarity, leading to changes in diagnostic practice at a national level.

Introduction

Between the extremes of full-blown manic-depressive illness (BP-I disorder) and strictly defined unipolar depression (UP disorder), there exists a prevalent spectrum of `soft' bipolar conditions characterized by major depressive episodes with less than syndromal mania (Akiskal, 1983). Bipolar-II disorder (BP-II) defined by major depressive episodes with recurrent hypomanic episodes and/or cyclothymic temperament is the prototype of the soft bipolar spectrum (Akiskal, 1996). Despite its inclusion in DSM-IV, the diagnosis of BP-II is still difficult to make in practice (Dunner and Tay, 1993): clinicians trained to recognize it appear better in diagnosing it than those using structured interviewing.

Patients suffering from a BP-II disorder usually seek help when depressed and most of them are recognized as `unipolar' and treated with antidepressants without any protection against such potential negative effects as mood switching, cycling, mixed states, chronicization and associated treatment resistance (Koukopoulous et al., 1980, Akiskal and Mallya, 1987, Wehr and Goodwin, 1987, Stoll et al., 1994, Altschuler et al., 1995). European psychiatrists are in some disadvantage in this regard, because ICD-10 (in common use in Europe), tends to equate bipolarity with more or less clear-cut mania (World Health Organization, 1992). We felt that in this context, an awareness of the clinical presentations of the entire soft bipolar spectrum represents an important issue in clinical practice. The clinical and public health significance of this issue is further underscored by emerging data on the very high prevalence of this spectrum of disorders (Akiskal and Mallya, 1987, Koukopoulous et al., 1990, Goodwin and Jamison, 1990, Cassano et al., 1992, Benazzi, 1997).

Section snippets

Aim

The over-arching purpose of the EPIDEP, and its companion EPIMAN (Akiskal et al., 1998), studies is to assist practising psychiatrists, whether in private, community or university settings, to recognize bipolarity in all of its varieties: especially psychotic, mixed manic, and bipolar II forms.

Preparatory to the ambitious aim of obtaining national French data on the full spectrum of bipolar disorders, between April 1992 and December 1994, the first author (EGH) held 40 round-tables in 26

General characteristics

Sixty-two percent of patients with MDE were out-patients. Seventy-four percent were female, and mean age (±SD) was 46 (±13) years. For 74% of patients, the current episode was part of a recurrent illness, and 50% had been previously hospitalized.

Diagnostic distribution at visit I

Classification of mood disorders at the end of Visit I was as follows: 48% recurrent UP, 24% first MDE, 22% BP-II, and 6% BP-I. The mean score (±SD) on HAM-D scale was 27 (±6), and on the Rosenthal additive scale 8 (±3).

Assessment and diagnostic distribution at visit II

By this visit, the mean score

Discussion

The main finding of this study is the high prevalence of BP-II in the total cohort of major depressive in- and/or outpatients examined by 48 investigators in 15 different regions of France. Apart from the 22% of patients previously known to have BP-II disorder, a systematic search for hypomanic episodes revealed that an additional 26.5% of `unipolar'patients (20% of those with first MDE and 30% of those with recurrent MDE) could be diagnosed as BP-II. This yielded a total prevalence of 40% for

Conclusion

Many clinical investigators (Endicott et al., 1985, Akiskal, 1983, Akiskal, 1994, Coryell et al., 1995) have argued for the distinct nature of BP-II disorder, within the bipolar spectrum, culminating in the DSM-IV acceptance of BP-II two decades after its initial delineation (Dunner et al., 1976). The EPIDEP study was designed to help clinicians in their daily practice to make precise and astute subtyping of bipolar disorders. Results on the first 250 patients entered showed that

Acknowledgements

Professor H.S. Akiskal (San Diego, USA) was the international advisor in collaboration with a French scientific committee, which included Professor J.F. Allilaire (Paris), Professor J.M. Azorin (Marseille), Professor M.L. Bourgeois (Bordeaux), and Professor D. Sechter (Besançon). The study is coordinated by Doctor E.G. Hantouche (Paris) in collaboration with Drs. J.P. Fraud (now retired) and L. Châtenet-Duchêne (both from CNS Department-Sanofi), and supported by an unrestricted grant from

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