The effects of centralised and specialised combined pharmacological and psychological intervention compared with decentralised and non-specialised treatment in the early course of severe unipolar and bipolar affective disorders--design of two randomised clinical trials

Lars Vedel Kessing, Hanne Vibe Hansen, Ellen Margrethe Christensen, Henrik Dam, Christian Gluud, Jørn Wetterslev, Early Intervention Affective Disorders (EIA) Group, D Klaus, Ejnar B Larsen, Martin B Jørgensen, Maj Vinberg, Rikke Engel, Flemming M Nilsson, Nana Hengstenberg, Birgitte B Bendsen, Hans M Jensen, Rie L Mikkelsen, Birgit Straasø, Jens Abraham, Lars Vedel Kessing, Hanne Vibe Hansen, Ellen Margrethe Christensen, Henrik Dam, Christian Gluud, Jørn Wetterslev, Early Intervention Affective Disorders (EIA) Group, D Klaus, Ejnar B Larsen, Martin B Jørgensen, Maj Vinberg, Rikke Engel, Flemming M Nilsson, Nana Hengstenberg, Birgitte B Bendsen, Hans M Jensen, Rie L Mikkelsen, Birgit Straasø, Jens Abraham

Abstract

Background: In unipolar, and bipolar affective disorders, there is a high risk of relapse that increases as the number of episodes increases. Naturalistic follow-up studies suggest that the progressive development of the diseases is not prevented with the present treatment modalities. It is not known whether centralised and specialised secondary care intervention initiated early after the onset of the diseases can prevent the progression and thereby improve the prognosis.

Methods: Two randomised clinical multi-centre trials comparing a centralised and specialised outpatient intervention program consisting of combined pharmacological and psychological intervention with standard decentralised psychiatric treatment. Patients discharged from their first, second, or third hospitalisation due to a manic episode or bipolar disorder (trial 1) or to a single depressive episode or recurrent depressive disorder (trial 2) were randomised. Central randomization for both trials were stratified for the number of hospitalisations and treatment centre. The primary outcome measure for the two trials is time to re-hospitalisation with an affective episode.

Discussion: These trials are the first to evaluate the effect of a centralised and specialised intervention in patients with early severe affective disorders. The trials used a pragmatic design comparing a specialised mood disorder clinic intervention with decentralised, non-specialised standard psychiatric treatment.

Trial registration: ClinicalTrials.gov: NCT00253071.

Figures

Figure 1
Figure 1
Anticipated statistical power estimations in Trials I and II. The anticipated power in the trials on the x-axis as a function of the sample size of the trials on the y-axis based on α = 0.05 and an anticipated hazard ratio of 0.65 and 6 month median time from randomisation to re-admission to hospital in the control group, 48 month inclusion period, and at least a 12 month follow up of all patients.

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