2-year course of bipolar disorder type I patients in outpatient care: Factors associated with remission and functional recovery

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Abstract

EMBLEM is a 2-year, prospective, observational study that enrolled patients initiating/changing oral treatment for an acute manic/mixed episode. This paper analysed remission and functional recovery in 1656 patients who entered the 2-year long-term phase. Cox models identified variables significantly associated with achieving remission and functional recovery at 2 years. Of these patients, 64% achieved remission and 34% achieved functional recovery. Patients with a higher CGI-BP overall score at baseline, who had depressive episodes in the year before inclusion and who had poor social functioning (work or social impairment, not living independently or without a spouse/partner) were less likely to achieve remission or recovery. Prescription of typical antipsychotics and prescription of antidepressants at the first visit of the long-term treatment phase (12 weeks) were independent predictors of lower remission and recovery rates. In conclusion, functional recovery occurred in approximately half of those who achieved remission. Impairment of work and social functioning was consistently associated with lower remission and recovery rates.

Introduction

Bipolar disorder is a chronic illness that is characterised by recurrent episodes of mania and depression that cause impairments in functioning and health-related quality of life (Rosa et al., 2008). Patients with bipolar disorder require both acute and maintenance therapy. The primary goal of acute treatment in manic patients is to improve symptoms whereas the primary goal of maintenance therapy is to achieve recovery and to prevent (or delay the time to) relapse (American Psychiatric Association, 2002, Keck, 2006, Rybakowski, 2007).

Recovery is a multidimensional concept in bipolar disorder which includes both symptomatic recovery and functional recovery. Symptomatic recovery (remission) is the resolution of the symptoms of the disorder, which should disappear or at least decrease to a minimal level. Functional recovery is the ability to return to an adequate level of functioning and includes an assessment of occupational status and living situation (Tohen et al., 2000, Tohen et al., 2003, Harvey, 2006). Previous studies have indicated that the majority of patients achieve symptomatic recovery but less than half achieve functional recovery within 24 months of a first manic/mixed episode (Tohen et al., 2000, Tohen et al., 2003). However, recovery rates are dependent on the criteria used to define recovery, the scales used to measure outcome, and the patient population studied (Martinez-Arán et al., 2007). For example, among patients with a first hospitalisation for affective psychosis, only 35% of patients achieved symptomatic recovery or had functional recovery during the 12-month follow-up (Strakowski et al., 1998).

Numerous factors may influence the course of illness in patients with bipolar disorder (see Nolen et al., 2004 for a review of predictors of outcome), but there is a lack of data from longitudinal studies in the naturalistic setting and most of the available data is from first-episode patients. Substance abuse and low socioeconomic status have been associated with delayed symptomatic recovery, whereas a higher socioeconomic status and good pre-morbid functioning (e.g. living independently, forming relationships, etc) was associated with faster functional recovery (Strakowski et al., 1998).

Analysis of the frequency and modifiers of remission and recovery requires studies with long follow-up periods. EMBLEM (European Mania in Bipolar Evaluation of Medication) is a large-scale 2-year European prospective observational study designed to evaluate the clinical, functional and economic outcomes of pharmacological treatment of patients with an acute manic or mixed episode of bipolar disorder.

The aims of the present paper are: (i) to describe those subgroups of patients with bipolar disorder who achieved remission and functional recovery following acute mania, and (ii) to determine the factors associated with remission and functional recovery during 2 years of follow-up.

Section snippets

Study design and patients

The EMBLEM study design, patient sample and baseline characteristics have been described in detail elsewhere (Goetz et al., 2007, Haro et al., 2006). Briefly, this was a 2-year prospective observational study conducted by 530 investigators across 14 European countries. The study enrolled 3459 eligible patients and consisted of two phases: (i) an acute treatment phase from baseline to 12 weeks, and (ii) a long-term treatment phase lasting up to 24 months post-baseline, with a maximum of 10 data

Results

A total of 1656 patients entered the long-term treatment phase of the study and had CGI-BP overall ratings available. Of these patients, 1060 (64%) achieved remission and 558 (34%) achieved functional recovery within the 2 years of follow-up. The number of completers in the study was 1538 (93%) at 12 months, 1458 (88%) at 18 months and 1338 (81%) at 2 years.

Table 1 summarises the socio-demographic and clinical characteristics of all eligible patients and the subgroups of patients achieving

Discussion

In recent years, efforts have been made to improve our understanding of the course of bipolar disorder by measuring remission and recovery in terms symptomatic and functional aspects, although there is still no consensus on the definitions of these terms (Martinez-Arán et al., 2007). In EMBLEM, we carefully defined these terms for the study population and found that a large proportion of patients achieved remission (64%), whereas only 34% achieved functional recovery during the 2 years of

Role of the funding source

The EMBLEM study was funded and supported by Eli Lilly and Company. Eli Lilly and Company was involved in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Contributors

All authors were involved in the initial study design. Data analysis was conducted by Jordan Bertsch. All authors contributed to the interpretation of the data and the preparation of this manuscript. All authors critically reviewed the manuscript.

Conflict of interest

Josep Maria Haro has consulted for Astra-Zeneca, Eli Lilly, Glaxo-Smith-Kline, and Lundbeck.

Ana González-Pinto has received grant support, acted as consultant, or given presentations for the following pharmaceutical companies: Almirall (Barcelona, Spain), Astra-Zeneca, Bristol-Myers-Squibb, Otsuka, Eli Lilly, Glaxo-Smith-Kline, Janssen-Cilag, Sanofi-Aventis, Lundbeck, Novartis, Organon and Pfizer.

Eduard Vieta received honoraria as member of the EMBLEM Advisory Board from Eli Lilly and Co, and

Acknowledgements

The authors would like to thank the EMBLEM Advisory Board for their participation in the design and conduct of the study. The EMBLEM Advisory Board included Prof. Bernard Sabbe (Belgium); Dr Jens Knud Larsen (Denmark); Prof. Hannu Koponen (Finland); Dr Isabelle Gasquet, Prof. Jean Michel Azorin (France); Dr Heinz Grunze (Germany); Prof. Willem Nolen, Prof. Jim van Os (The Netherlands); Dr Trond Aarre (Norway); Prof. Dr med Jules Angst (Switzerland); Dr John Cookson, Prof. Martin Knapp (UK); Dr

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