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Some Notes and Definitions

Reviewers of studies of the clinical course of MDD have had to contend with variable definitions (or lack of any definition) of recovery and recurrence, variable follow-up intervals in different studies, and countless potential predictors that were assessed in multiple ways. The following sections enumerate some of the issues that have to be considered in examining the extant literature.

Recovery and Recurrence: Methodological Issues

An accurate summary of the findings on recovery from depression is made difficult by the fact that studies have differed in their approaches to this topic. Investigators in the National Institute of Mental Health (NIMH) Collaborative Study of Depression were among the first to propose an operational definition of recovery from an episode of mood disorder as 8 consecutive weeks with either no symptoms or only one or two mild symptoms.24,25 Recurrence was therefore the onset of a new episode after the required, relatively symptom-free interval. Within this naming convention (which was eventually used by many investigators), relapse signified the return of symptoms of a given episode for a person who appeared to have been on the way to recovery (showed symptomatic improvement) but did not end up meeting criteria for recovery. Alternate definitions of recovery from a mental disorder and the distinction between recovery, relapse, and remission, have been presented by Frank et al.26 Although recent approaches to recovery have included consideration of the patient’s sense of psychological well-being,27 the current overview uses the above-noted definition of being essentially symptom-free for at least 8 weeks.

The variability across studies in rates of assessment, follow-up periods, and statistical treatment of the results has presented further challenges to reviewers. First, because recovery and recurrence are both time-dependent outcomes, they are best determined via longitudinal, repeated assessments; a single “follow-back” evaluation after many years is likely to yield inaccurate information. Second, because observation times typically vary across cases, and because some cases may be lost to follow-up while some others may not manifest the outcome of interest during the observation period, some form of “survival analysis” is the most suitable computational procedure for follow-up data. Thus, survival analyses provide more valid estimates regarding recovery and recurrence than do cross-sectional tallies.

The evidence from various studies indicates that to estimate the outcome of a given MDD episode in a sample of patients, the minimum follow-up period should be between 3 and 5 years, counting from the onset of the episode. However, it is difficult to estimate “true recovery” from the disorder because the risk of an episode of MDD continues across the life span.28 Nevertheless, follow-up intervals of 10 or more years should allow reasonable estimates of the proportion of cases that have remained free of depression and thus may have recovered from the disorder (not only from a given episode).

However, when estimating the likelihood of recovery from a given MDD episode (or its duration), another important consideration is the start point used in computations. For MDD, episode-specific recovery, or duration, should be computed from the date of the onset of the given episode. Unfortunately, in various pediatric studies, recovery was estimated from the time of entry into the study29 or from the time when treatment was first initiated.30 By disregarding the prior length of the episode, this method introduces a bias in the recovery estimates.

In contrast to much of the adult and pediatric literature on the course of depression, publications from the NIMH Collaborative Study of Depression in clinical samples of adults have uniformly used operational definitions of recovery and recurrence in connection with MDD episodes, gathered information via a repeated assessment research design, included long-term follow-up, and consistently applied appropriate longitudinal statistical approaches to model the data. Thus, the Collaborative Study results on recovery and recurrence of MDD in adults will be used to provide a broader context for the findings on pediatric-onset MDD.

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