The effects of centralised and specialised intervention in the early course of severe unipolar depressive disorder: a randomised clinical trial

Hanne Vibe Hansen, Ellen Margrethe Christensen, Henrik Dam, Christian Gluud, Jørn Wetterslev, Lars Vedel Kessing, Early Intervention Affective Disorders (EIA) Trial Group, Klaus Damgård Jakobsen, Ejnar Bundgaard Larsen, Martin Balslev Jørgensen, Maj Vinberg, Rikke Engel, Flemming Mørkeberg Nilsson, Nana Hengstenberg, Birgitte Bjerg Bendsen, Hans Mørch Jensen, Rie Lambæk Mikkelsen, Birgit Straasø, Jens Abraham, Hanne Vibe Hansen, Ellen Margrethe Christensen, Henrik Dam, Christian Gluud, Jørn Wetterslev, Lars Vedel Kessing, Early Intervention Affective Disorders (EIA) Trial Group, Klaus Damgård Jakobsen, Ejnar Bundgaard Larsen, Martin Balslev Jørgensen, Maj Vinberg, Rikke Engel, Flemming Mørkeberg Nilsson, Nana Hengstenberg, Birgitte Bjerg Bendsen, Hans Mørch Jensen, Rie Lambæk Mikkelsen, Birgit Straasø, Jens Abraham

Abstract

Background: Little is known on whether centralised and specialised combined pharmacological and psychological intervention in the early phase of severe unipolar depression improve prognosis. The aim of the present study was to assess the benefits and harms of centralised and specialised secondary care intervention in the early course of severe unipolar depression.

Methods: A randomised multicentre trial with central randomisation and blinding in relation to the primary outcome comparing a centralised and specialised outpatient intervention program with standard decentralised psychiatric treatment. The interventions were offered at discharge from first, second, or third hospitalisation due to a single depressive episode or recurrent depressive disorder. The primary outcome was time to readmission to psychiatric hospital. The data on re-hospitalisation was obtained from the Danish Psychiatric Central Register. The secondary and tertiary outcomes were severity of depressive symptoms according to the Major Depression Inventory, adherence to medical treatment, and satisfaction with treatment according to the total score on the Verona Service Satisfaction Scale-Affective Disorder (VSSS-A). These outcomes were assessed using questionnaires one year after discharge from hospital.

Results: A total of 268 patients with unipolar depression were included. There was no significant difference in the time to readmission (unadjusted hazard ratio 0.89, 95% confidence interval 0.60 to 1.32; log rank: χ(2) = 0.3, d.f. = 1, p = 0.6); severity of depressive symptoms (mood disorder clinic: median 21.6, quartiles 9.7-31.2 versus standard treatment: median 20.2, quartiles 10.0-29.8; p = 0.7); or the prevalence of patients in antidepressant treatment (73.9% versus 80.0%, p = 0.2). Centralised and specialised secondary care intervention resulted in significantly higher satisfaction with treatment (131 (SD 31.8) versus 107 (SD 25.6); p<0.001).

Conclusions: Centralised and specialised secondary care intervention in the early course of severe unipolar depression resulted in no significant effects on time to rehospitalisation, severity of symptoms, or use of antidepressants, but increased patient satisfaction.

Trial registration: ClinicalTrials.gov NCT00253071.

Conflict of interest statement

Competing Interests: LVK has been a consultant for Bristol-Myers Squibb, Eli Lilly, Lundbeck, AstraZenica, Pfizer, Wyeth, Servier, and Janssen-Cilag. HVH, EMC, HD, CG and JW have no competing interests. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Consort flow diagram.
Figure 1. Consort flow diagram.
Figure 2. Time to readmission for patients…
Figure 2. Time to readmission for patients treated in the mood disorder clinic versus standard care (all patients, N = 268).
Figure 3. Time to readmission for patients…
Figure 3. Time to readmission for patients treated in the mood disorder clinic versus standard care (only patients with two or more prior hospitalisations, N = 80).

References

    1. Kessing LV, Hansen MG, Andersen PK, Angst J. The predictive effect of episodes on the risk of recurrence in depressive and bipolar disorders - a life-long perspective. Acta Psychiatr Scand. 2004;109(5):339–344.
    1. Solomon DA, Keller MB, Leon AC, Mueller TI, Lavori PW, et al. Multiple recurrences of major depressive disorder. Am J Psychiatry. 2000;157(2):229–233.
    1. Tohen M, Hennen J, Zarate CM, Jr, Baldessarini RJ, Strakowski SM, et al. Two-year syndromal and functional recovery in 219 cases of first-episode major affective disorder with psychotic features. Am J Psychiatry. 2000;157(2):220–228.
    1. Kessing LV. Cognitive impairment in the euthymic phase of affective disorder. Psychol Med. 1998;28(5):1027–1038.
    1. Kessing LV, Nilsson FM. Increased risk of developing dementia in patients with major affective disorders compared to patients with other medical illnesses. J Affect Disord. 2003;73(3):261–269.
    1. Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry. 2006;63(5):530–538.
    1. Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet. 2003;361(9358):653–661.
    1. Jacobsen JC, Hansen JL, Storebø OJ, Simonsen E, Gluud C. The effect of cognitive therapy versus ‘treatment as usual’ in patients with major depressive disorder. A systematic review of randomized clinical trials with meta-analysis and trial sequential analysis. PLoS One. 2011;6(8):e22890. doi: .
    1. Kessing LV, Hansen MG, Andersen PK, Angst J. The predictive effect of episodes on the risk of recurrence in depressive and bipolar disorders - a life-long perspective. Acta Psychiatr Scand. 2004;109(5):339–344.
    1. Kessing LV, Hansen MG, Andersen PK. Course of illness in depressive and bipolar disorders. Naturalistic study, 1994–1999. Br J Psychiatry. 2004;185:372–377.
    1. Solomon DA, Keller MB, Leon AC, Mueller TI, Lavori PW, et al. Multiple recurrences of major depressive disorder. Am J Psychiatry. 2000;157(2):229–233.
    1. Demyttenaere K, Adelin A, Patrick M, Walthere D, Katrien dB, et al. Six-month compliance with antidepressant medication in the treatment of major depressive disorder. Int Clin Psychopharmacol. 2008;23(1):36–42.
    1. Maj M, Veltro F, Pirozzi R, Lobrace S, Magliano L. Pattern of recurrence of illness after recovery from an episode of major depression: a prospective study. Am J Psychiatry. 1992;149(6):795–800.
    1. Melfi CA, Chawla AJ, Croghan TW, Hanna MP, Kennedy S, et al. The effects of adherence to antidepressant treatment guidelines on relapse and recurrence of depression. Arch Gen Psychiatry. 1998;55(12):1128–1132.
    1. Hansen HV, Kessing LV. Adherence to antidepressant treatment. Expert Rev Neurother. 2007;7(1):57–62.
    1. Von KM, Goldberg D. Improving outcomes in depression. BMJ. 2001;323(7319):948–949.
    1. Badamgarav E, Weingarten SR, Henning JM, Knight K, Hasselblad V, et al. Effectiveness of disease management programs in depression: a systematic review. Am J Psychiatry. 2003;160(12):2080–2090.
    1. Oxman TE, Dietrich AJ, Schulberg HC. The depression care manager and mental health specialist as collaborators within primary care. Am J Geriatr Psychiatry. 2003;11(5):507–516.
    1. Dietrich AJ, Oxman TE, Williams JW, Jr, Schulberg HC, Bruce ML, et al. Re-engineering systems for the treatment of depression in primary care: cluster randomised controlled trial. BMJ. 2004;329(7466):602.
    1. van Os TW, van den Brink RH, Tiemens BG, Jenner JA, van der MK, et al. Are effects of depression management training for General Practitioners on patient outcomes mediated by improvements in the process of care? J Affect Disord. 2004;80(2–3):173–179.
    1. Wells K, Sherbourne C, Schoenbaum M, Ettner S, Duan N, et al. Five-year impact of quality improvement for depression: results of a group-level randomized controlled trial. Arch Gen Psychiatry. 2004;61(4):378–386.
    1. Warner-Schmidt JL, Duman RS. Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus. 2006;16(3):239–249.
    1. Kessing LV, Sondergard L, Forman JL, Andersen PK. Antidepressants and dementia. J Affect Disord. 2009;117(1–2):24–29.
    1. Berk M, Hallam K, Lucas N, Hasty M, McNeil CA, Conus P, et al. Early intervention in bipolar disorders: opportunities and pitfalls. Med J Aust. 2007;187(7 Suppl):S11–S14.
    1. Zwarenstein M, Treweek S, Gagnier JJ, Altman DG, Tunis S, et al. Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ. 2008;337:a2390.
    1. Kessing LV, Hansen HV, Christensen EM, Dam H, Gluud C, et al. 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. Trials. 2011;12(1):32.
    1. Kessing LV, Hansen HV, Hougaard E, Hvenegaard A, Albæk J. Preventive outpatient treatment in affective disorders. 2006. Results from a Health Tecnology Assessment (HTA). Copenhagen: National Board of Health DCfEaHTA, editor. Ref Type: Report.
    1. Dam H, Bendsen BB, Jakobsen K, Larsen EB, Nilsson FM, et al. [Large differences in treatment of depression between departments of psychiatry]. Ugeskr Laeger. 2010;172(46):3183–3187.
    1. National Board of Health. Reference program for adults with unipolar depression (in Danish: Referenceprogram for unipolar depression hos voksne). 2007. Ref Type: Report.
    1. Bauer M, Whybrow PC, Angst J, Versiani M, Moller HJ. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and continuation treatment of major depressive disorder. World J Biol Psychiatry. 2002;3(1):5–43.
    1. Bauer M, Whybrow PC, Angst J, Versiani M, Moller HJ. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance treatment of major depressive disorder and treatment of chronic depressive disorders and subthreshold depressions. World J Biol Psychiatry. 2002;3(2):69–86.
    1. Munk-Jorgensen P, Mortensen PB. The Danish Psychiatric Central Register. Dan Med Bull. 1997;44(1):82–84.
    1. Klassifikation af sygdomme. Systematisk del. International Statistical Classification of Diseases and Health Related Problems. 1993. Tenth revision (Danish). Munksgaard, editor. Copenhagen.
    1. Bech P, Olsen LR. [Discovering depression]. Ugeskr Laeger. 2001;163(14):1980–1982.
    1. Bech P, Rasmussen NA, Olsen LR, Noerholm V, Abildgaard W. The sensitivity and specificity of the Major Depression Inventory, using the Present State Examination as the index of diagnostic validity. J Affect Disord. 2001;66(2–3):159–164.
    1. Olsen LR, Jensen DV, Noerholm V, Martiny K, Bech P. The internal and external validity of the Major Depression Inventory in measuring severity of depressive states. Psychol Med. 2003;33(2):351–356.
    1. Hirschfeld RM, Williams JB, Spitzer RL, Calabrese JR, Flynn L, et al. Rapport DJ, Russell JM, Sachs GS, Zajecka J: Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157(11):1873–1875.
    1. Hirschfeld RM, Holzer C, Calabrese JR, Weissman M, Reed M, et al. Validity of the mood disorder questionnaire: a general population study. Am J Psychiatry. 2003;160(1):178–180.
    1. Ruggeri M, Lasalvia A, Bisoffi G, Thornicroft G, Vazquez-Barquero JL, et al. Satisfaction with mental health services among people with schizophrenia in five European sites: results from the EPSILON Study. Schizophr Bull. 2003;29(2):229–245.
    1. Kessing LV, Hansen HV, Ruggeri M, Bech P. Satisfaction with treatment among patients with depressive and bipolar disorders. Soc Psychiatry Psychiatr Epidemiol. 2006;41(2):148–155.
    1. Wing JK, Babor T, Brugha T, Burke J, Cooper JE, et al. SCAN. Schedules for Clinical Assessment in Neuropsychiatry. Arch Gen Psychiatry. 1990;47(6):589–593.
    1. Bock C, Bukh JD, Vinberg M, Gether U, Kessing LV. Validity of the diagnosis of a single depressive episode in a case register. Clin Pract Epidemiol Ment Health. 2009;5:4.:4.
    1. Kessing LV, Hansen MG, Andersen PK, Angst J. The predictive effect of episodes on the risk of recurrence in depressive and bipolar disorders - a life-long perspective. Acta Psychiatr Scand. 2004;109(5):339–344.
    1. de Maat SM, Dekker J, Schoevers RA, de JF. Relative efficacy of psychotherapy and combined therapy in the treatment of depression: a meta-analysis. Eur Psychiatry. 2007;22(1):1–8.
    1. Keller MB, McCullough JP, Klein DN, Arnow B, Dunner DL, et al. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med. 2000;342(20):1462–1470.
    1. Burns T. End of the road for treatment-as-usual studies? - Br J Psychiatry. 2009;195(1):5–6.
    1. NICE. Depression: Management of depression in primary and secondary care. 2004. NICE, National Institute for Clinical Excellence.
    1. Danish National Board of Health. 2007. Guidelines for treatment of unipolar disorder (Danish: Referenceprogram for unipolar depression hos voksne)
    1. Hirschfeld RM, Williams JB, Spitzer RL, Calabrese JR, Flynn L, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157(11):1873–1875.
    1. Hirschfeld RM, Holzer C, Calabrese JR, Weissman M, Reed M, et al. Hazard E: Validity of the mood disorder questionnaire: a general population study. Am J Psychiatry. 2003;160(1):178–180.

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