Long-term effects of depression treatment
Authors: Rudolf Uher, Barbara Pavlova
Journal: The Lancet Psychiatry (2016)

In most cases, depression is a recurrent or chronic condition that affects individuals over the course of their lifetime.1Judd LL Akiskal HS Maser JD et al.A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders.Arch Gen Psychiatry. 1998; 55: 694-700Crossref PubMed Scopus (691) Google Scholar The realisation that depression needs long-term treatment2Andrews G Should depression be managed as a chronic disease?.BMJ. 2001; 322: 419-421Crossref PubMed Scopus (195) Google Scholar has not been matched by adequate evidence of the long-term effects of specific treatments, leaving a major gap in evidence for the clinical practice of psychiatry. The most commonly used long-term treatment is maintenance antidepressants. However, for most antidepressant drugs, the efficacy of treatment lasting more than 1 year is unknown. The absence of evidence of the long-term therapeutic effects of antidepressant drugs leaves uncertainty and invites controversy. In The Lancet Psychiatry, the Article by Nicola Wiles and colleagues3Wiles NJ Thomas L Turner N et al.Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial.Lancet Psychiatry. 2016; (published online Jan 6.)http://dx.doi.org/10.1016/S2215-0366(15)00495-2Google Scholar brings perhaps the most substantial body of evidence of the long-term effects of a treatment of major depressive disorder: a comprehensive report of the effectiveness and cost-effectiveness of adjunctive cognitive behavioural therapy (CBT) in a 3·5 year follow-up of the CoBalT trial. In the CoBalT trial, 469 primary care patients with depressive symptoms of at least moderate severity despite adherence to antidepressant treatment were randomly allocated to be offered a course of 12 to 18 sessions of individual CBT or to continue their usual care that included antidepressants. Most participants had chronic and severe depression with comorbid anxiety disorders. Those who were offered the adjunctive CBT had fewer depressive symptoms and were more likely to fulfil criteria for response at 6 and 12 month follow-up.4Wiles N Thomas L Abel A et al.Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial.Lancet. 2013; 381: 375-384Summary Full Text Full Text PDF PubMed Scopus (227) Google Scholar In the present study, Wiles and colleagues report the results of a 46 months follow-up. Outcomes were available from roughly 60% of participants. They showed that the benefits of CBT were fully maintained. More than 3 years after the end of treatment, participants who were allocated to CBT continued to do better on several self-reported outcomes and the effect sizes were similar to those at 6 and 12 months. Participants who received CBT scored roughly four points lower on the Beck Depression Inventory (mean score of 19·2 with CBT vs 23·4 without CBT), two points lower on the Patient Health Questionnaire, had fewer anxiety symptoms, and were twice as likely to meet criteria for response or remission. These differences in outcomes were maintained for more than 3 years whereas four-fifths of participants in both groups continued to take antidepressant drugs. An accompanying health economic analysis shows that add-on individual CBT provides exceptionally good value for money. The CoBalT findings are in agreement with previous smaller studies5Fava GA Ruini C Rafanelli C Finos L Conti S Grandi S Six-year outcome of cognitive behavior therapy for prevention of recurrent depression.Am J Psychiatry. 2004; 161: 1872-1876Crossref PubMed Scopus (247) Google Scholar, 6Paykel ES Scott J Cornwall PL et al.Duration of relapse prevention after cognitive therapy in residual depression: follow-up of controlled trial.Psychol Med. 2005; 35: 59-68Crossref PubMed Scopus (106) Google Scholar that suggested that the effects of CBT for depression can last for years. Although antidepressant drugs and brain stimulation treatments are effective only as long as the treatment is continued, CBT provides long-term benefits without continued treatment or booster sessions, which is probably because the participants learn skills that they continue practising after the treatment stops. Consequently, discontinued CBT might be as effective as continued treatment with antidepressant medication and more effective than antidepressant medication that is discontinued.7Cuijpers P Hollon SD van Straten A Bockting C Berking M Andersson G Does cognitive behaviour therapy have an enduring effect that is superior to keeping patients on continuation pharmacotherapy? A meta-analysis.BMJ Open. 2013; (published online April 26)https://doi.org/10.1136/bmjopen-2012-002542Crossref PubMed Scopus (170) Google Scholar CBT has been shown to improve functional outcomes, including employment.8Fournier JC DeRubeis RJ Amsterdam J Shelton RC Hollon SD Gains in employment status following antidepressant medication or cognitive therapy for depression.Br J Psychiatry. 2015; 206: 332-338Crossref PubMed Scopus (27) Google Scholar The present study adds strong evidence that the lasting therapeutic effects of CBT are maintained even in individuals with severe, chronic, and comorbid depression who did not respond well to antidepressants. In combination with previous smaller studies, the results of the long-term follow-up of CoBalT suggest that CBT should be routinely offered to individuals with major depressive disorder who do not have satisfactory improvement with antidepressants alone. This conclusion leaves a quandary about the availability of high quality CBT in routine clinical setting. The fact that very few CoBalT participants received CBT as part of their usual care during the 3·5 year follow-up reflects poorly on the availability of structured evidence-based therapies even in a country that invested substantially in their provision. Questions might be raised about whether similar long-term benefits might be achieved with other types of psychological treatments or with less intensive forms of therapy delivery, such as group, self-help, computerised, or internet-delivered psychological treatments. However, no similar evidence for long-term efficacy in severely affected individuals is available for any less intensive treatment, and the one similar long-term study9Frank E Kupfer DJ Perel JM et al.Three-year outcomes for maintenance therapies in recurrent depression.Arch Gen Psychiatry. 1990; 47: 1093-1099Crossref PubMed Scopus (920) Google Scholar of another psychological therapy suggested that, even with regular booster sessions, interpersonal psychotherapy did not match the maintenance effect of a continued antidepressant. Individual CBT is presently the only psychological treatment with robust evidence for improving long-term outcomes of major depressive disorder. Notwithstanding the positive results, the CoBalT trial also reminds us that even a combination of antidepressants and individual CBT does not provide a complete solution for major depressive disorder.4Wiles N Thomas L Abel A et al.Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial.Lancet. 2013; 381: 375-384Summary Full Text Full Text PDF PubMed Scopus (227) Google Scholar Years after receiving individual CBT and continued antidepressant treatment, the average CoBalT participant still scored 19 points on the Beck Depression Inventory, which puts them into the moderately depressed range. Although data for functional outcomes such as employment are missing, these symptoms probably continue to seriously affect quality of life and productivity. Therefore, clinicians and researchers should focus on strategies to increase the efficacy of the existing treatments and on developing more effective treatments for major depressive disorder. We declare no competing interests. Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trialCBT as an adjunct to usual care that includes antidepressants is clinically effective and cost effective over the long-term for individuals whose depression has not responded to pharmacotherapy. In view of this robust evidence of long-term effectiveness and the fact that the intervention represented good value-for-money, clinicians should discuss referral for CBT with all those for whom antidepressants are not effective. Full-Text PDF Open Access