The prevalence of treatment-resistant depression (TRD) appears to be increasing. A recent meta-analysis found TRD to be a problem in nearly 40% of depressed patients, a dramatic increase from the 1990s when it was reported to affect 10-15% of patients [1, 2]. While this difference may be related to differences in how the studies were performed, if correct, it would suggest a process in which TRD is occurring in response to environmental, biological or clinical factors. Psychiatrists do not have control over environmental factors, but we do have direct control over clinical factors and hence a duty to examine these. For example, TRD may be related to inadequate dosing of antidepressants [3] or antide-pressant tolerance [4]. Alternatively, there are reasons to believe that antidepressant treatment itself may contribute to a chronic depressive syndrome [5, 6].
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