Depression relapse: importance of a long-term perspective
Authors: Roger Mulder
Journal: The Lancet (2015)

Emil Kraepelin's demarcation between dementia praecox and manic depressive illness defined affective disorder as a remitting and recurring disease. He considered that only long-term outcome was useful in assessing accuracy of diagnosis and treatment response in patients.1Kraepelin E Dementia praecox and paraphrenia. E & S Livingstone, Edinburgh1919Google Scholar The more recent interest in the outcome of single mood episodes probably indicates motives to register and market drugs rather than assisting clinical practice. This interest has resulted in many 4–8 week randomised trials but few well designed long-term studies in patients with depression. There is now increasing evidence that Kraepelin was right. Mood disorders are generally recurring, and the relevant measure of clinical success is long-term functioning rather than the outcome of a single mood episode.2Andrews G Should depression be managed as a chronic disease?.BMJ. 2001; 322: 419-421Crossref PubMed Scopus (199) Google Scholar In secondary and tertiary care, less than a third of patients recover and remain well in the 18 months after an episode of depression,3Mulder RT Frampton CM Luty SE Joyce PR Eighteen months of drug treatment for depression: predicting relapse and recovery.J Affect Disord. 2009; 114: 263-270Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar whereas in general practice and community studies, the proportion of patients with recurrence is between 35% and 65%.4Steinert C Hofmann M Kruse J Leichsenring F The prospective long-term course of adult depression in general practice and the community. A systematic literature review.J Affect Disord. 2014; 152–54: 65-75Summary Full Text Full Text PDF Scopus (101) Google Scholar Treatment needs to focus on maintenance and prevention of relapse as well as on the acute mood episode. The most established treatment for prevention of relapse and recurrence is maintenance antidepressant medication. Studies have consistently reported a reduction in the odds of relapse of about 50–70%.5Geddes JR Carney SM Davies C et al.Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review.Lancet. 2003; 361: 653-661Summary Full Text Full Text PDF PubMed Scopus (692) Google Scholar, 6Borges S Chen Y Laughren T et al.Review of maintenance trials for major depressive disorder: a 25-year perspective from the US Food and Drug Administration.J Clin Psychiatry. 2014; 75: 205-214Crossref PubMed Google Scholar However, many patients might not wish to remain on medication or cannot tolerate the side-effects. Alternative non-medication strategies would obviously be desirable. Mindfulness-based cognitive therapy (MBCT) was developed as an explicit intervention to reduce relapse and recurrence in depression. MBCT teaches people who have had depression that negative feelings and thoughts will recur and that, rather than worrying or ruminating about these experiences, it is possible to become aware of and disengage from them, thereby preventing a downward spiral into depression.7Segal ZV Williams JMG Teasdale JD Mindfulness-based cognitive therapy for depression: a new approach to preventing relapse. Guilford Press, New York2002Google Scholar Although cognitive behavioural therapy and interpersonal therapy also have evidence of efficacy in the prevention of relapse in depressed patients8Beshai S Dobson KS Bockting CL Quigley L Relapse and recurrence prevention in depression: current research and future prospects.Clin Psychol Rev. 2011; 31: 1349-1360Crossref PubMed Scopus (103) Google Scholar neither were developed specifically for this purpose. Willem Kuyken and colleagues' study,9Kuyken W Hayes R Barrett B et al.Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.Lancet. 2015; (published online April 21.)http://dx.doi.org/10.1016/S0140-6736(14)62222-4PubMed Google Scholar published in The Lancet, of mindfulness-based cognitive therapy in the prevention of depressive relapse or recurrence is therefore timely. It is a pragmatic long-term study done in general practice, where most depression is treated. The randomised trial compared MBCT with maintenance antidepressants in a large sample of patients with recurrent depression in the UK. 212 patients were randomly assigned to MBCT and 212 to maintenance antidepressant treatment, and the time to relapse or recurrence of depression did not differ between treatment groups over 24 months (hazard ratio 0·89, 95% CI 0·67–1·18). The authors' interpretation of the findings is carefully worded: there is no support for MBCT being superior to maintenance antidepressants in preventing depressive relapse. Despite this apparent negative result, the findings have substantial clinical significance. Kuyken and colleagues' findings, if benchmarked against the studies of maintenance antidepressant therapy, provide evidence that MBCT might offer a similar ongoing protective effect as that of maintenance antidepressants. MBCT therefore provides an alternative effective treatment for patients who cannot tolerate or do not wish to have maintenance antidepressant therapy. Because it is a group treatment that reduces costs and the number of trained staff needed, it might be feasible to offer MBCT as a choice to patients in general practice. Pooling all trial data comparing MBCT and maintenance antidepressant treatment (which is limited to three studies), as Kuyken and colleagues did,9Kuyken W Hayes R Barrett B et al.Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.Lancet. 2015; (published online April 21.)http://dx.doi.org/10.1016/S0140-6736(14)62222-4PubMed Google Scholar resulted in a risk reduction of 24% for MBCT compared with maintenance antidepressants (risk ratio 0·76 95% CI 0·59–0·98). Perhaps all patients with recurrent depression should be offered MBCT. We therefore have a promising new treatment that is reasonably cost effective and applicable to the large group of patients with recurrent depression. The next obvious question is whether there are specific effects of MBCT that confer this decreased risk of relapse or whether any structured group psychotherapy would produce similar results. Ongoing studies of mechanism of action are promised by the authors. If the research in long-term treatment of personality disorders is any guide, they are likely to find that general factors such as a manualised approach, active supportive therapists, a focus on patients' sense of agency and management of life situations are most important,10Bateman AW Gunderson J Mulder R Treatment of personality disorder.Lancet. 2015; 385: 735-743Summary Full Text Full Text PDF PubMed Scopus (190) Google Scholar rather than specific factors related to mindfulness theory. Depression remains a disabling condition with high prevalence and a large clinical burden. Despite the increased use of drugs, the long-term outcome of mood disorders has not improved in the modern era.11Mulder RT Frampton CM Outcome of mood disorders before psychopharmacology: a systematic review.Aust N Z J Psychiatry. 2014; 48: 224-236Crossref PubMed Scopus (14) Google Scholar Having an alternative non-medication strategy to reduce relapse is an important means to help patients with depression. I declare no competing interests. Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trialWe found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the prevention of depressive relapse in individuals at risk for depressive relapse or recurrence. Both treatments were associated with enduring positive outcomes in terms of relapse or recurrence, residual depressive symptoms, and quality of life. Full-Text PDF Open Access