Data obtained from the Netherlands Mental Health Survey and Incidence Study (NEMESIS) indicate a high risk of recurrence among patients treated for major depression (Hardeveld et al. Psychol Med 2013;43:39-48). The study included 687 subjects with major depressive disorder (DSM-III-R) in remission for at least six months and prospectively followed-up for three years.

The estimated rate of recurrence of a major depressive episode was 13.2% at 5 years, 23.2% at 10 years, and 42.0% at 20 years. Risk factors for recurrence on multivariate analysis were younger age, a higher number of previous episodes of depression, severe last episode, negative youth experiences and ongoing difficulties.

Similarly, recurrence risk factors in the Depression Evaluation Longitudinal Therapy Assessment (DELTA) study in the Netherlands were a higher number of previous episodes, more residual symptoms, and coping style (ten Doesschate et al. J Clin Psychiatry 2010 Aug;71:984-991); the study updated results from a previous study (Bockting et al. J Clin Psychiatry 2006;67:747-755).

An early remission (HAM-D < 7 by week 6) or early response (>50% decrease in HAM-D-17) to treatment also appear to be associated with better one-year outcomes (Ciudad et al. J Clin Psychiatry 2012;73:185-191).

It should be noted, however, that estimates of response, remission and recurrence depend on the clinical criteria used, and cut-off values have not been established. A recent study reported that the most sensitive/specific measures for defining remission were cut-off values of HAM-D-21 < 7, HAM-D-17 < 6, MADRS < 7 or BDI < 12 (Riedel et al. J Psychiatr Res 2010;44:1063-1068). Response was best defined as a >47% decrease from baseline on the HAM-D-21 or BDI, >57% decrease in HAM-D-17, or >46% on MADRS.

Comment
Dr. Arun Ravindran: This recent publication by Hardeveld et al. confirms previous reports and clinical experience that recurrences are common in patients with major depression.  Furthermore, it adds to the evidence that with such recurrences, functional impairments worsen and the likelihood of non-response increases.  It confirms the need for careful assessment, regular monitoring and tailored intervention for this vulnerable population and further provides information on factors that predict higher risk of recurrence.

How can the risk of recurrence be reduced?

• Persistence of residual symptoms predicts recurrences, thus there is a need to treat patients to full remission.  This may entail the use of psychological and pharmacological therapies as adjuncts to first-line antidepressants.
• It is clear that the risk of recurrence increases after each episode and there is a need for maintenance therapy and encouragement of treatment adherence.  Most patients with major depression need at least a year of antidepressant maintenance after their initial episode of illness, and a longer maintenance period with subsequent ones.  Evidence-based psychological therapies such as CBT provide additional help in the prevention of such recurrences.