By Ellen Feldman, MD
Altru Health System, Grand Forks, ND
Dr. Feldman reports no financial relationships relevant to this field of study.
SYNOPSIS: Maintenance antidepressants or mindfulness-based cognitive therapy aimed at tapering or discontinuing antidepressants are both effective interventions for prevention of recurrent depression.
SOURCE: Kuyken W, 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;386:63-73.
Summary Points
- This study compared both clinical efficacy and cost-effectiveness of maintenance antidepressants and structured group therapy (aimed at reducing or discontinuing antidepressant use) in a population of U.K. adults at risk for recurrent depression.
- Both interventions reduce expected rates of remission in depression; there is no clear statistical evidence of superiority for either intervention.
- In this British study, mindfulness-based cognitive therapy (MBCT-TS) was not more cost-effective than maintenance antidepressants.
- MBCT-TS may show more effectiveness in patients with a history of childhood abuse (potential area of further study).
“Good morning, Pooh Bear,” said Eeyore gloomily. “If it is a good morning,” he said. “Which I doubt,” said he.
“Why, what’s the matter?”
“Nothing, Pooh Bear, nothing. We can’t all, and some of us don’t. That’s all there is to it.”
“Can’t all what?” said Pooh, rubbing his nose.
“Gaiety. Song-and-dance. Here we go round the mulberry bush.”
From Winnie the Pooh by A.A. Milne
Untreated depression has chronic health and wellness implications. Relapse risk following an episode of acute depression can approach 80%.1,2 The current recommendation for prevention of recurrent depression is to maintain antidepressant treatment for 2 years from symptom relief.3 Recognizing that some patients prefer or require alternatives to conventional treatment and that adherence to antidepressant regimes tend to be problematic, this 2-year study compared efficacy and cost-effectiveness of antidepressant maintenance therapy with a structured non-pharmacologic alternative: group sessions of mindfulness-based cognitive therapy aimed at discontinuing or tapering antidepressants (MBCT-TS). The original aim of the study was to see if this psycho-social intervention would be more effective in preventing relapse than maintenance antidepressant medication.
Mindfulness-based cognitive therapy (MBCT) blends the teachings of cognitive-behavioral therapy with the meditative techniques of mindfulness-based stress reduction.4 MBCT is typically a group intervention delivered in a standardized manner with a focus on recognizing and addressing specific thought patterns that impact recurrent depressive episodes. It is meant to be utilized during episodes of remission (not during actively depressed periods.)
Studies of MBCT have shown this technique has promise in reducing depression relapse rates in more chronically depressed and higher-risk patients.5,6,7 This is the first study attempting a head-to-head comparison of MBCT-TS with maintenance antidepressants. In this study, MBCT-TS was delivered in the standard group format and combined with a medication-tapering regime delivered in conjunction with primary care.
Participants were recruited from general practice populations across diverse areas of the United Kingdom. Eligibility criteria included adults with a diagnosis of major depressive disorder in full or partial remission, three or more past episodes of major depression, and currently taking a therapeutic dose of an antidepressant. Exclusion criteria included most comorbidities (medical and psychiatric), as well as persistent self-harm, current major depression, and current formal psychotherapy.
Of the initial 424 patients in the study, 212 were each assigned to one of two groups: maintenance antidepressant therapy via regular visits with a family physician over the 2-year period or MBCT-TS group therapy with one of four therapists (eight groups weekly for 8 weeks then four refresher sessions approximately every quarter over the 2- year period.) Participants in the MBCT-TS group also met regularly with their family physician over the study period to taper antidepressants and monitor response.
All patients were re-assessed for evidence of recurrence of depression at five set time intervals during the study period. A relapse was defined as symptoms that met DSM-IV criteria for major depression. The relapse rate for both groups was comparable and less than expected without intervention. The researchers also noted and studied the number of depression-free days, any residual depressive symptoms not meeting full criteria, any medical or psychiatric comorbidities, quality of life, and cost-effectiveness.
Of the 424 participants in this 2-year study, 366 remained active in the study at the last data collection point. Numbers were remarkably similar for each group at each time interval. In the maintenance antidepressant group, 162 remained on a therapeutic dose of antidepressants throughout the study period. In the MBCT-TS group, 176 completed four or more group MBCT sessions. Of these, 124 discontinued their medication entirely, 29 reduced the total dose (no specifics given), and 23 did not change their dose of antidepressant medication. (See Figures 1 and 2.)
Figure 1: Maintenance Antidepressant Group |
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Figure 2: MBCT-TS Group |
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176 completing ≥ 4 MBCT sessions
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There was no statistical significance between primary or secondary outcome results between the groups. Ninety-four patients (44%) in the original MBCT-TS group relapsed as did 100 patients (47%) in the original antidepressant maintenance group. None of the secondary measures showed a standardized mean difference of > 0.4 at any of the five follow-up time points.
There was a noted interaction involving the presence of childhood abuse. MBCT-TS patients with self-reported childhood abuse had a lower risk of relapse when compared to the maintenance antidepressant group (49 of 105 [47%] patients relapsed compared vs 65 of 111 [59%] patients relapse.) On the other hand, the patients with a low severity of childhood abuse in the MBCT-TS treatment group did not perform as well as their counterparts in the maintenance antidepressant group (44 of 105 [42%] relapse vs 35 of 101 [35%] relapse). (See Figure 3.)
Figure 3: Relapse in Specific Groups: High vs Low Risk Based on Childhood Abuse |
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When determining cost effectiveness, these authors looked at several different measures, including total health care costs and societal costs, which included out-of-pocket and productivity costs for patients. P values ranging from 0.681 to 0.800 indicated the absence of statistical significance between these groups when looking at these designated parameters.
COMMENTARY
The results of this study are important on several levels and raise several questions, not the least of which revolves around the importance of considering an “exit strategy” when initiating antidepressant treatment.
A primary message appears fairly straightforward: There exists an effective alternative to maintenance antidepressants in the treatment of recurrent depression. Why is this important? In 2014, the Rochester Epidemiology Project looked at several facets of antidepressant use. The researchers calculated the prevalence of use in their adult population (year 2011) at 14.4%, representing an increase from 10.8% in 2005.8
A different study in late 2013 looking at patterns and trends in adult antidepressant use found an overall significant increase in prevalence of antidepressant use in U.S. adults during the first decade of 2000.9
Most relevant today is that this increase was strongest for long-term use of antidepressants in adults treated by general medical providers, who currently prescribe the bulk of antidepressants in the United States.10 It is not much of a stretch to extrapolate that this trend could be affected if clear alternatives to the use of long-term antidepressants are found effective. Chief among concerns for patients on long-term antidepressants is an emerging concern about the potential for weight gain and development of type 2 diabetes.11
However, before switching patients from maintenance antidepressants, physicians should consider several points. Recall that this study included two groups — one group met regularly with physicians to maintain antidepressant dosage and the other group engaged in MBCT but also met regularly with physicians to taper antidepressants. The design of the study failed to include a group of patients who attempted to taper or discontinue antidepressants without MBCT, but still with the assistance of their primary care practitioner. Thus, it is difficult to definitively state that the MBCT-TS is responsible for the success of this second group at reducing the rate of recurrent depression.
The cost-effectiveness analysis in this study may not be globally applicable. Health care costs, out-of-pocket costs, and medication costs in the United Kingdom may differ from such costs in the United States and other countries. Regional availability of MBCT-TS or even of cognitive-behavioral therapists may differ not only across the United States, but globally as well. In the United States, out-of-pocket and societal costs will vary with specific health care plans. Nevertheless, the approach taken by this team of researchers to analyze costs bears merit as long it is understood in context.
The importance of this study lies in alerting practitioners to consider a role for specific group therapy (MBCT-TS) as an alternative to maintenance antidepressants when treating patients to prevent recurrent depression. The findings imply the most effective use of this therapy is found with patients who have had significant history of childhood abuse; this is consistent with other studies examining the use of MBCT in treating recurrent depression. The author’s future goal to try to identify the specific mechanism(s) of action of MBCT should help bring more clarity to this point.
An in-depth review of the study leads to a consideration that a course of careful tapering of antidepressants in low-risk patients with recurrent depression may also have a role in the prevention of recurrent episodes of depression. As work is done in this area, more potential choices and definitive algorithms of treatment should emerge, allowing a more targeted approach to treating and preventing depression from a chronic and debilitating course.
REFERENCES
- Derek R. Prevalence and clinical course of depression: A review. Clin Psychol Rev 2011;31:1117-1125.
- Mulder RT, et al. Eighteen months of drug treatment for depression: Predicting relapse and recovery. J Affect Disord 2009;114:263-270.
- Borges S, 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;75:205-214.
- Segal ZV, et al. Mindfulness-based Cognitive Therapy for Depression: A New Approach to Preventing Relapse. New York: Guilford Press; 2002.
- Teasdale JD, et al. Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. J Consult Clin Psychol 2000;68:615-623.
- Piet J, Hougaard E. The effect of mindfulness-based cognitive therapy for prevention of relapse in recurrent major depressive disorder: A systematic review and meta-analysis. Clin Psychol Rev 2011;31:1032-1040. doi:10.1016/j.cpr.2011.05.002.
- Williams JMG, et al. Mindfulness-based cognitive therapy for preventing relapse in recurrent depression: A randomized dismantling trial. J Consult Clin Psychol 2014;82:275-286.
- Zhong W, et al. Time trends of antidepressant drug prescriptions in men versus women in a geographically defined US population. Arch Woman’s Mental Health 2014; 17:485-492. doi: 10.1007/s00737-014-0450-7. Epub 2014 Aug 13.
- Mojtabai R, Olfson M. National trends in long-term use of antidepressant medications: Results from the US National Health and Nutrition Examination Survey. J Clin Psychiatry 2014;75:169-177.
- Barkil-Oteo A. Collaborative care for depression in primary care: How psychiatry could “troubleshoot” current treatments and practices. Yale J Biol Med 2013;86:139-146.
- Wu C, et al. Long-term antidepressant use and the risk of type 2 diabetes mellitus: A population-based, nested case-control study in Taiwan. J Clin Psychiatry 2014;75:31-38.
Maintenance antidepressants or mindfulness-based cognitive therapy aimed at tapering or discontinuing antidepressants are both effective interventions for prevention of recurrent depression.
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