Naturalistic studies of depressed outpatients suggest that many will stop medication prematurely on their own despite recommendations for continuation4
. Another group of patients may be unsuitable for long term antidepressant treatment because of emergent clinical issues such as pregnancy or drug interactions5,15,35
. We studied a preventive MBCT intervention in recurrently depressed patients who were discontinued from antidepressant medication after achieving full remission and compared their long term outcomes to those who stayed on medication or received placebo. Our findings indicated that the quality of remission achieved during the acute phase interacted with the type of prevention treatment patients received to determine relapse outcomes during the subsequent maintenance phase. For patients whose acute phase remission was marked by periodic symptoms flurries20,21
, discontinuing ADM and receiving MBCT or continuing with M-ADM significantly lowered relapse risk compared to discontinuation to PLA. These results are in accord with previous reports that the temporal features of remission or the presence of residual symptoms are correlated with poorer acute and maintenance phase outcomes36,37
and that reduction of this risk with targeted treatment is beneficial34,38,39
. Of note, in this group of patients in need of continued intervention, MBCT and M-ADM were equally effective.
Surprisingly, for patients whose acute phase remission was stable, there was no differential impact on survival between the treatments we studied. While the 50% relapse rate in PLA is in line with other studies in which antidepressants were discontinued following continuation treatment (e.g. Keller et al,40
: 47.3%, Montgomery et al.,41
: 55%), the protective effects of active treatment were smaller. What explains this discrepancy? First, since sample characteristics are known to vary across studies it makes it difficult to compare absolute relapse rates from other trials. Second, stable and unstable remitters did not differ on a number of demographic or clinical history variables known to impact relapse risk. One possibility is that stable remitters may have had lower motivation to comply with treatment in the maintenance phase where, having shown a robust clinical response, they faced a two out of three chance of discontinuation. Secondary analyses of treatment mediators may help to clarify these group differences.
In spite of its growing evidence base, exactly how MBCT exerts its preventive effect is not fully understood. Because the daily practice of mindfulness invariably cues exposure to negative emotions, patients learn how to uncouple their habitual responses to dysphoria-triggering cues26,42
in favor of responses informed by a metacognitive relationship to the very same mental contents. Data on the neural changes associated with mindfulness training support this view. Mindfulness practitioners demonstrated less neural reactivity to sadness provocation relative to a group of novices, as seen via both reduced activation of posterior cortical midline structures and in reduced suppression of right viscerosomatic networks such as the insula and right lateral prefrontal cortex27
. Reduced suppression in the insula and subgenual ACC have also been observed in depressed patients treated with cognitive therapy43
and may point to a common locus of effect. The affect regulation afforded by these growing capacities, may make it easier for patients to adopt lifestyle and behavioural strategies that support recovery, a sine qua non of any effective maintenance treatment.
This study had a number of limitations. Reporting a lack of difference between M-ADM and MBCT in both stable and unstable remitters raises the risk of Type II error, in which, due to low power, an important effect may be missed. One way to address this involves calculating E44
, the expected number of relapse events required to replicate the reported hazard ratios for the comparisons between M-ADM and MBCT. The analysis revealed that in both stable and unstable groups, detecting hazard ratios different from one would require extremely large samples (N > 1000). This suggests that the lack of significance between M-ADM and MBCTs is less likely attributable to under sampling, and more likely due to a very small measured effect.
As with any long term treatment study, there is a possibility for bias through differential retention of patients. Only slightly more than half of the patients initially enrolled were eligible for randomization into the maintenance phase, most due to nonresponse but also because once having achieved remission they declined to move into the maintenance phase. This raises the question of how closely the randomized sample represents the initial group. Although we relied on randomization to equate the treatment groups on baseline characteristics, differential retention cannot be fully ruled out for clinical features we did not consider.
It is well established that patients with recurrent depression require care past the point of episode remission. For those, unwilling or unable to tolerate maintenance antidepressant treatment our data suggest that MBCT offers equal protection from relapse over 18 months and highlights the importance of maintaining at least one active long term treatment in unstable remitters.