This meta-analytic review of the world's published literature provides current answers to four questions about preventing relapse–recurrence in MDD. First, we found that relapse–recurrence is quite common among responders to A-CT. We estimate that about half of responders to A-CT (54%) will relapse–recur within 2 years if they do not receive continuation-phase treatment. Second, we nonetheless found that A-CT reduces relapse–recurrence significantly compared with acute-phase pharmacotherapy discontinued, whether A-CT is combined with acute-phase pharmacotherapy (22% reduction) or not (23% reduction). This is important because whereas prescribers continue pharmacotherapy, patients frequently do not (Olfson, Marcus, Tedeschi, & Wan, 2006
). We recommend that patients, clinicians, and authors of treatment guidelines consider the preventive effect of A-CT compared with pharmacotherapy in their acute-phase treatment selection.
Expressing our findings as NNT informs expectations about the impact of CT on a patient population. NNT specifies the average number of patients that clinicians would need to treat with the more effective treatment (e.g., A-CT) instead of with the less effective treatment (e.g., pharmacotherapy alone) to realize a savings of 1 patient's relapse–recurrence. We found that for every 4 to 5 patients treated with A-CT, instead of or in addition to acute-phase pharmacotherapy, 1 additional patient's relapse–recurrence would be prevented. The potential public health significance of this effect becomes apparent when considering the incidence of depression. For example, if we assume, using current epidemiological data, that (a) ~35,000,000 people have MDD each year in the United States (Kessler et al., 2003
), (b) ~16% (5,600,000) of persons with depression receive adequate pharmacotherapy (A. S. Young, Klap, Sherbourne, & Wells, 2001
), (c) ~50% (2,800,000) of patients with depression respond to acute-phase treatment (Hollon, Jarrett, et al., 2005
), and (d) ~72% (2,016,000) of patients discontinue pharmacotherapy within 90 days (Olfson et al., 2006
), then the potential savings achieved by treating these patients with A-CT is roughly 448,000 relapses–recurrences annually.
Although A-CT prevents some relapse–recurrence compared with acute-phase pharmacotherapy, the high rate of relapse–recurrence after acute treatments supports the need for continuation-phase treatments. Third, we found that C-CT reduces relapse–recurrence significantly compared with nonactive comparison conditions (i.e., assessment-only) over the period that the continuation-phase treatment is in effect (21% reduction) and after continuation-phase discontinuation at later follow-ups (29% reduction). Finally, we found that C-CT reduces relapse–recurrence compared with other active continuation-phase treatments (e.g., pharmacotherapy) at similar levels at the end of continuation-phase treatment (12% reduction) and at later follow-up (14% reduction). We recommend that patients and clinicians consider C-CT after remission during acute treatments to reduce risk for relapse, and perhaps recurrence. For every 4 to 5 patients treated with C-CT instead of discontinuing acute treatment, and for every 8 to 9 patients treated with C-CT instead of other continuation-phase treatments (treatment as usual and/or pharmacotherapy), 1 additional patient's relapse–recurrence would be prevented. Future research is necessary before recommendations can be made regarding the effects of maintenance-phase CT in delaying or preventing recurrence.
The quantity and quality of data available for meta-analysis temper our recommendations and suggest improvements needed in future clinical trials. Of importance, the number of studies available for some contrasts was small (e.g., three to five studies). Consequently, some conclusions about CT's effects on relapse–recurrence may shift substantially (e.g., relapse–recurrence after A-CT vs. other depression-specific psychotherapies) as future research becomes available. Moreover, studies included in our analyses treated mostly White patients, leaving open questions of the generalizability of our findings to other ethnic groups. Additional clinical trials investigating the effects of CT on relapse and recurrence compared with other treatments, and including ethnically diverse samples, would be clear and important contributions to the field.
Several variables moderated estimates of relapse–recurrence after A-CT in our meta-analysis. As more studies become available, researchers may be able to clarify the unique effects of these design and analysis issues on relapse–recurrence estimates. In the meantime, we report moderators of relapse–recurrence estimates for consideration in the design and interpretation of clinical trials. For example, studies that provided relapse–recurrence estimates using categorical proportions rather than longitudinal survival estimates, and studies with assessment strategies leaving gaps rather than completing covering the follow-up period, had lower relapse–recurrence rates. Clearly, studies with longer follow-up periods had higher relapse–recurrence rates.
Because the concepts of relapse and recurrence are inherently longitudinal, assessment and statistical methods also must be longitudinal. We recommend that researchers use instruments such as the Longitudinal Interval Follow-up Evaluation (Keller et al., 1987
) to capture relapse–recurrence events more completely than do static assessments (e.g., an assessment at 12 months post acute-phase treatment focusing on symptoms during the past month) that may miss patients who relapse–recur but then remit. Similarly, we recommend that researchers consider time-to-event (“survival”) analyses (e.g., Kaplan–Meier product-limit and Cox proportional hazard models) to estimate relapse–recurrence rates and remain vigilant to improved or supplemental methodologies for longitudinal analysis. Survival analyses provide more accurate estimates of relapse–recurrence than do simple proportions when data sets contain patients who do not relapse–recur by the end of the follow-up period or attrit (“censored” cases; Cohen, Cohen, West, & Aiken, 2003
; Keller, Shapiro, Lavori, & Wolfe, 1982
). Different rates of attrition between conditions, especially, have the potential to bias comparisons of CT with other treatments and increase the need for survival analyses.
Only about half of the studies in our review documented adherence and/or competence in CT, and we recommend that future researchers use standard instruments (e.g., Hollon et al., 1988
; Liese, Barber, & Beck, 1995
; J. Young & Beck, 1980
) to do so. Moreover, some otherwise excellent studies did not meet our inclusion criteria because they reported data inconsistently with consensus definitions of relapse and recurrence (Frank et al., 1991
; Rush et al., 2006
). Consistent with our analyses, we recommend that the term relapse
(e.g., meeting MDE criteria) be applied only to patients who have first achieved some level of remission
(e.g., several weeks with minimal depressive symptoms and no MDE) and that recurrence
(e.g., meeting MDE criteria) be applied only to patients who have first achieved recovery
(e.g., several months without meeting criteria for MDE). Idiosyncratic strategies for reporting depressive symptom data may limit the accumulation of knowledge across studies.
Several studies reported internal moderators that clinicians and researchers should consider. Not surprisingly, C-CT may be more necessary for patients at higher risk for relapse–recurrence, including those with a history of more MDEs (Bockting et al., 2005
; Ma & Teasdale, 2004
; Teasdale et al., 2000
), an earlier onset of MDD (Jarrett et al., 2001
), and unstable remission during A-CT (Jarrett et al., 2001
). Developing knowledge of moderators is useful clinically because A-CT appears to have an enduring, albeit likely finite, effect for about half of the A-CT responders. For example, clinicians can advise responders finishing a course of A-CT about their chances of relapse–recurrence with and without C-CT given their level of residual symptoms (Jarrett, Vittengl, & Clark, 2005
, in preparation). Certainly, attention to documenting the number of MDEs patients have experienced previously is essential in studying relapse and recurrence.
A number of studies excluded details about the amount of treatment received by patients, including CT sessions completed and extraprotocol treatment. These variables have the potential to influence interpretation of CT's benefits significantly. Our reading of the literature suggests that research reports often include the number of CT sessions offered to patients (i.e., sessions in the protocol), but less often include the number of sessions actually received by patients—usually a smaller number and arguably the more important variable (e.g., Hollon et al., 1992
; Jarrett et al., 2001
). Similarly, research reports often omit the amount and types of extraprotocol treatment that patients receive (e.g., after the end of acute-phase treatment). Moreover, strategies for handling extraprotocol treatment vary from viewing any extraprotocol treatment as part of naturalistic follow-up (e.g., Simons, Murphy, Levine, & Wetzel, 1986
), to censoring from analyses patients receiving extraprotocol treatment without a documented relapse–recurrence (e.g., Hollon, DeRubeis, et al., 2005
), to including extraprotocol treatment referral and seeking in relapse–recurrence definitions (e.g., Blackburn, Eunson, & Bishop,1986
). We recommend that researchers measure and report receipt of CT and extraprotocol treatment, test the associations of these variables with relapse–recurrence within and between treatment conditions (e.g., as covariates in survival analyses), and describe the criteria applied when censoring outcomes during survival analyses.
Our meta-analyses do not clarify mechanisms of A-CT's and C-CT's reduction of relapse–recurrence. We speculate that CT teaches compensatory skills (e.g., managing cognition and social relationships) that some patients implement successfully to reduce internal and external risks for relapse–recurrence (Barber & DeRubeis, 2001
; Jarrett, 1989
; Jarrett & Kraft, 1997
). Comparable learning may not take place with pharmacotherapy alone, and A-CT responders may further increase compensatory skills when they receive C-CT. Future research might profitably address questions of optimal “dosing” with CT (i.e., number of sessions completed over variable intervals plus duration and focus of treatment phase) for distinct subgroups, as well as mediation of outcomes through development of specific compensatory skills or other hypothesized active therapeutic ingredients. Methodologically rigorous and consistent investigation of relapse and recurrence in MDD will facilitate acquisition of knowledge about their prevention through A-CT, C-CT, and other effective treatments.