Is duration of untreated illness important in depression as well ? Jl Affective disorders.Jan.2014


Long duration of untreated illness (DUI) is a strong predictor of relapse and poor outcomes in psychotic disorders. Recognition of this has led to early intervention services for psychosis in many countries. It is not known whether DUI has similar impact on prognosis in depression. Nature of  mood disorders (self reported past affective states, high prevalence of milder affective states, variable routes to care, issues in defining DUI in a recurrent disorder, DUI vs Duration of untreated episode (DUE) etc) makes it difficult to study DUI.

So, do have enough evidence to believe that DUI is relevant in unipolar depression? Lucio Ghio , Simona Gotelli, Maurizio Marcenaro, Mario Amore, and Werner Natta from University of Genoa reports the results of the first systematic review and meta analysis on this question.

All studies investigating either DUI or DUE in major depression was included.They included RCTs and observational studies. The main outcome  measure was response and/or remission in relation to the time elapsed from the onset of adequate treatment, as measured by standardised rating scales for depression.


10 studies met inclusion criteria. Nine were observational and one was a clinical trial. Five each studied DUI and DUE.

Response : Two studies provided data on  patients’ response to treatment as the outcome variable.Pooled data on the response to treatment in relation to DUI from these two studies showed an overall positive effect. i.e. a shorter DUI was associated with a better  response to treatment (RR 1.70).

Remission :  Only three studies ( de Diego-Adeliño et al., 2010; Okuda et al., 2010; Bukh et al., 2013) reported comparable data and were used for pooling data. Shorter DUI (= shorter than eight weeks) was associated with better remission rates (RR 1.65). Note that  follow-up was only 8 weeks in two of these studies and the third one (Bukh et al) was a retrospective study.

DUE: data not evident to comment.

It is possible that the concepts of DUE and DUI are essentially different. Kindling hypothesis of depression (i.e.  with recurrent episodes, the role of environmental stressors diminish, and episodes become more ‘autonomous’. The associated neurobiological/ psychological changes might be contributing to poor treatment response) might be a relevant consideration in explaining this.

Limitations: Very few studies in this area. Available studies differ in  designs, outcome measures, and follow-up periods.Strength of conclusions limited by these factors.

Conclusions: Available limited evidence suggest that reduction in the no-treatment interval is particularly important in a patient’s first episode of depression. Early treatment is likely to give better response and remission.  The association between the DUE in recurrent depression and clinical outcomes are less evident.

Summary of the article:

Duration of untreated illness and outcomes in unipolar depression: A systematic review and meta-analysis.

Ghio L, Gotelli S, Marcenaro M, Amore M, Natta W. J Affect Disord. 2014 Jan;152-154:45-51.

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