December 9, 2010 — Mindfulness-based cognitive therapy (MBCT) is as effective in preventing relapse in patients with recurrent major depressive disorder (MDD) as maintenance antidepressant monotherapy, the current standard of care, new research suggests.

In this study, 84 patients with MDD were randomized after achieving remission to receive continued antidepressant use, MBCT, or placebo. For the patients deemed "unstable remitters" with periodic symptom flurries, the relapse rates during 18 months of follow-up did not differ between the MBCT and antidepressant groups (28% vs 27%) but was significantly higher in the placebo group (71%).

"We were very pleased to find that [MBCT] could hold its own against active pharmacotherapy," lead study author Zindel V. Segal, PhD, head of the Cognitive Behavior Therapy Clinic in the Clinical Research Department at the Center for Addiction and Mental Health (CAMH) in Toronto, Ontario, Canada, and professor of psychiatry at the University of Toronto, told Medscape Medical News.

Dr. Zindel V. Segal

He noted that "this makes it an important option" for a number of different subpopulations who become depressed, such as pregnant women. "Coming off medication can trigger a relapse. But now people can come off their medication knowing that there is an option that is nonpharmacological and protects them to the same degree," said Dr. Segal.

The investigators write that the findings also highlight "the importance of maintaining at least 1 long-term active treatment" in unstable remitters.

"I think the take-home message is that clinicians need to consider sequential treatment of mood disorders, where one treatment approach such as an antidepressant can be used in the acute phase to get people well and then people can be switched to another approach that's maybe psychological in nature to help them stay well," said Dr. Segal.

"This would give patients a larger envelope of care so they can deal with acute symptoms and also engage in lifestyle and behaviors that will increase wellness over the long term."

The study was published in the December issue of Archives of General Psychiatry.

40% Discontinuation

"Relapse and recurrence after recovery from [MDD] are common and debilitating outcomes that carry enormous personal, familial, and societal costs," write the researchers.

They note that although maintenance with antidepressant monotherapy is the current standard of care for prevention of relapse, up to 40% of MDD patients don't take their medication.

"Data from the community suggest that many depressed patients discontinue antidepressant medication far too soon, either because of an unwillingness to take medicine for years or side effects that have become unbearable, such as sexual side effects. So the importance of having alternatives to continued antidepressant use is a priority," said Dr. Zindel.

MBCT is a nonpharmacological, group-based intervention that teaches patients how to monitor for possible relapse triggers, changing automatic reactions associated with depression into opportunities for useful reflection. They also practice "health-enhancing behaviors" such as meditation or yoga.

"It's learning how to pay attention to present moment experiences and to ground oneself in an awareness of what is going on with both emotions and body," Dr. Zindel explained.

"People often aren't aware that emotional triggers can start a downward spiral of depression," he added. "In [MBCT], people learn how to regulate their emotions more effectively by paying attention and to work with their feelings in ways that don't involve pushing issues aside. Instead, it gives them more options for dealing with emotions in an adaptive way, making relapse less likely."

For this study, 160 patients between the ages of 18 and 65 years with recurrent MDD were enrolled at outpatient clinics at CAMH and at St. Joseph's Healthcare in Hamilton, Ontario, Canada.

Of these, 84 (63% female; mean age, 44 years; mean number of previous MDD episodes, 4.7) met remission criteria after 8 months of antidepressant monotherapy. Remission was defined for this study as a score of 7 or less on the Hamilton Rating Scale for Depression (HRSD).

Although 51% of these patients were classified as unstable remitters, defined as individuals who had intermittently higher scores on the HRSD, their average scores were low enough to qualify for remission. The other 49% were classified as stable remitters because their HRSD scores were consistently low.

All remitted patients were then randomized to receive either continued use of antidepressant monotherapy (n = 28), tapered use of antidepressant for 4 weeks plus placebo with clinical management (n = 30), or tapered use of antidepressant plus 8 weekly group sessions of MBCT (n = 26).

In addition to their group sessions, the MBCT patients received daily homework assignments consisting of taped awareness exercises and developing an action plan for ways to respond to early warning signs of relapse/recurrence. They were also offered an optional monthly refresher class at the conclusion of the weekly sessions.

Psychiatric visits and clinical assessments were conducted for all patients at regular intervals throughout 18 months of follow-up. Relapse was defined as a return of MDD symptoms for at least 2 weeks.

Equal Relapse Protection

Results showed no significant between-group differences in relapse rates for all study patients: 38% for MBCT, 46% for antidepressant maintenance, and 60% for placebo (P = .66).

However, both MBCT and antidepressant maintenance significantly reduced the risk for subsequent relapse in unstable remitters compared with placebo (P = .01 and P = .03, respectively).

Compared with placebo, the hazard ratio for MBCT for the unstable remitters was 0.26 (95% confidence interval [CI], 0.09 – 0.79), whereas antidepressant therapy had a hazard ratio of 0.24 (95% CI, 0.07 – 0.89). There was no change in risk between the 2 active treatment groups.

For stable remitters, there was no significant difference in relapse rates between the 3 groups: 62% for MBCT, 59% for antidepressant maintenance, and 50% for placebo.

"For those unwilling or unable to tolerate maintenance antidepressant treatment, MBCT offers equal protection from relapse during an 18-month period," write the study authors.

"Sequential intervention may keep more patients in treatment and thereby reduce the high risk of recurrence that is characteristic of this disorder," Dr. Segal added.

He noted that "this is still a relatively novel approach" and is not available in many centers outside larger cities. "Given the effectiveness of this approach, I think our next challenge is to find out how to get more people either trained in this treatment or to provide ways of delivering it perhaps online so that patients can have greater access to it.

"Taking antidepressants may seem to be the easier treatment for patients, as we're asking them to devote 20 to 30 minutes of their day to practicing mindfulness. But in the long run I think this approach will pay real dividends," said Dr. Segal.

Exciting Alternative

Dr. Stuart J. Eisendrath

"These are very exciting findings," Stuart J. Eisendrath, MD, professor of clinical psychiatry at the University of California–San Francisco (UCSF), director of the UCSF Depression Center, and director of clinical services at Langley Porter Psychiatric Hospitals and Clinics, told Medscape Medical News.

"[MDD] is a relapsing disorder, so finding ways of preventing that is crucial and finding alternatives to medication is very important," said Dr. Eisendrath, who was not involved with this study. "For a variety of reasons, some people don't like to take medications on an ongoing basis, so having an alternative intervention that could help individuals prevent relapse is exciting."

He added that this treatment approach "also enhances the individual's self-efficacy. It gives them a way that they can feel they have some control over their own likelihood of relapsing or not."

However, Dr. Eisendrath noted that he found the way the authors characterized remission in the patients "was interesting" in that any of the 3 interventions were equally effective for those with a stable remission, including placebo. "What was the nature of the support of the nonspecific effects of the various interventions? It would be interesting to see further studies that would tease that information out."

Still, overall, "I think the takeaway point is that if people have an unstable remission, it's crucial that they have a maintenance strategy to prevent relapse. And this study points out that [MBCT] is equally effective to maintenance antidepressants as 1 such strategy," he concluded.

The study was funded by a grant from the National Institute of Mental Health. The study authors and Dr. Eisendrath reported no relevant financial relationships. This study was presented in part at the 43rd Annual Meeting of the Association for Behavioral and Cognitive Therapies.

Arch Gen Psychiatry. 2010;67:1256-1264.