ReviewWhat happens to patients with treatment-resistant depression? A systematic review of medium to long term outcome studies
Introduction
Depression represents a substantial public health burden owing to its high prevalence (Jenkins et al., 1997, Kessler et al., 2005, Kessler et al., 1994, Robins et al., 1984, Weissman et al., 1988), association with premature death and disability (Lee and Murray, 1988, World Health Organisation, 2001), and considerable cost (Greenberg et al., 2003, Thomas and Morris, 2003). A large proportion of the burden caused by depression is likely to be attributable to treatment-resistant depression (TRD) (George et al., 2005, Greden, 2001, Malhi et al., 2005). There are several reasons for this. First, TRD itself is common: applying often used definitions of response it affects 20–30% of those with depression (Souery et al., 2006, Trivedi et al., 2006), with this figure rising to as high as 60% if TRD is defined – as it probably should be – as absence of remission (Greden, 2001, Trivedi et al., 2006). Second, duration and severity of illness, both of which are higher in TRD, are important determinants of disease burden (Ustun and Kessler, 2002). Third, patients with TRD are more likely to suffer from comorbid physical and mental disorders, to experience marked and protracted functional impairment, and to incur higher medical and mental healthcare costs (Fava, 2003, Keller, 2005, Kornstein and Schneider, 2001, Nelsen and Dunner, 1995, Sackeim, 2001). Thus, in order to reduce the substantial burden caused by depression, TRD should be one of the central focuses of epidemiological and interventional research.
It is only recently that researchers have focussed on TRD, and attempted to improve treatment in this area. As well as treatment challenges, there is uncertainty about the longer term outcome of patients with TRD. In order to be able to judge the efficacy of enhanced treatments specifically targeted to improve the outcome of TRD, it is necessary to understand the long term outcome of TRD in current practice. We undertook a systematic review of short and longer term outcome studies of TRD in order to assess how people with TRD fare in the longer term. We were not interested in acute treatment trials of TRD, but in studies which provided data on the longer term outcome of those who either had ongoing depressive symptoms after treatment or who had previously experienced TRD but responded successfully to treatment.
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Search methods
Relevant outcome studies were identified using electronic searches of MEDLINE (1960 — June Week 1 2008), EMBASE (1974 — June Week 1 2008), PsycINFO (1967 — June Week 1 2008) and PubMed. Bibliographies of identified articles were also manually searched for relevant publications. We used the following key words to identify the studies: RESIST⁎; REFRACTOR⁎; DIFFICULT; INTRACTABLE; ANTIDEPRESS⁎; DEPRESS⁎ (Berlim and Turecki, 2007); THERAPY or TREATMENT, REFRACT⁎; RESISTANT; NON-RESPOND⁎;
Results
We initially identified 816 potentially relevant publications. Of these, 654 were mainly aetiological articles (neurobiological, structural and risk factor) and opinion pieces and were excluded. Further 87 studies were excluded because they were either general follow-up studies of depression or descriptive studies of TRD. Sixty eight studies were excluded because they were primarily reports of treatment trials and further three were excluded because they were follow-up studies of older
Quality of included studies
The studies included were not primarily aimed at assessing the longer term outcome of TRD. This may partly account for the heterogeneity and limitation of the studies. Our attempt to use a rather broad and inclusive definition that we felt was likely to capture most patients with probable TRD might have also introduced heterogeneity.
Given the nature of TRD itself and its current conceptualisation, the cohort in this review is predominantly formed of patients from secondary and tertiary
Role of funding source
Nothing declared.
Conflict of interest
No conflict declared.
Acknowledgement
We are grateful to Sonya Lipczynska, librarian at the Institute of Psychiatry, for assistance in literature search.
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