DEFINITION AND EPIDEMIOLOGY OF TREATMENT-RESISTANT DEPRESSION
Section snippets
DEFINITION OF TREATMENT RESISTANCE
Treatment-resistant depression patients may be defined as those who fail to respond to standard doses (i.e., significantly superior to placebo in double-blind studies) of antidepressants administered continuously for a minimum duration of 6 weeks. This definition of treatment-resistant depression, although more liberal than some, has the advantage of taking feasibility of treatment into account. For example, 12 continuous weeks of monotherapy would be a more conservative definition for the
TREATMENT RESISTANCE VERSUS RELAPSE OR RECURRENCE
A recent review102 illustrated that much of the literature on treatment-resistant depression has failed to distinguish between the concepts of resistance (failure of the current episode to remit) and the concepts of relapse or recurrence (return of symptoms to the point of meeting criteria for major depressive episode after an initial response). These concepts often cannot be distinguished on the basis of their clinical features without a longitudinal assessment. To complicate this issue
NONRESPONSE VERSUS PARTIAL RESPONSE
Clinical studies of antidepressant drug treatments clearly have shown that many depressed patients improve significantly with treatment but still do not reach acceptable levels of functioning and well-being. These patients often are referred to as partial responders as opposed to nonresponders (i.e., those who show little or no improvement with treatment). Similarly, Frank et al36 used the term partial remission to describe a period during which an improvement of sufficient magnitude is
PROSPECTIVE VERSUS RETROSPECTIVE ASSESSMENT OF TREATMENT RESISTANCE
One of the major methodologic issues in treatment-resistant depression studies is whether assessment of resistance is performed prospectively or retrospectively. The prospective method of determination of treatment resistance is clearly preferable as there is a tremendous risk for misclassification with retrospective determination. Possible recall biases are likely to greatly affect patients' self-report of response to previous drug trials. Such recall bias becomes quite evident in clinical
CHRONICITY VERSUS TREATMENT RESISTANCE
An important distinction needs to be made between treatment-resistant depression and chronic depression. The term chronic refers to a prolonged, lingering condition and is derived from the Greek word chronos, or time, whereas treatment resistance connotes a condition that is difficult to treat regardless of its duration.59 Chronicity may appear as a protracted major depressive episode, as unremitting dysthymia, or as subsyndromal depression. Although chronicity may be the result of true
OTHER METHODOLOGIC ISSUES IN THE ASSESSMENT OF TREATMENT RESISTANCE IN DEPRESSION
Dyck22 has proposed that one of the major problems in assessing treatment resistance in depression is the failure to adequately conceptualize or specifically define treatments. When examining resistance to treatment, clinicians must focus on the efficacy of acute treatment only to avoid the risk of misclassification of relapses or recurrences as failure to respond. The acute treatment phase is defined as the period beginning with the diagnosis of a mood disorder episode and ending after
PREDICTORS OF NONRESPONSE OR PARTIAL RESPONSE IN DEPRESSION
As mentioned by Paykel73 in a review of the literature, attempts to use biologic markers as predictors of failure to recover have not yet been successful. Significantly shortened REM latencies, however, may predict treatment resistance.53 There are also a number of clinical factors, including some specific subtypes of major depression, that have been found to predict poorer response to antidepressant treatment. For example, family history of affective illness appeared to predict worse outcome,2
EPIDEMIOLOGY OF TREATMENT-RESISTANT MAJOR DEPRESSIVE DISORDER
Even though the prevalence of depression has been reported to vary from 2.6% to 5.5% in men and from 6.0% to 11.8% in women,57 no study has assessed systematically the epidemiology of treatment-resistant depression. For this reason, we decided to attempt to generate estimates of the prevalence of treatment resistance in populations with unipolar major depressive disorder through a compilation of rates of partial response and nonresponse in recently published clinical trials. Because most
SUMMARY
Our results suggest that between 29% and 46% of depressed patients fail to respond fully with antidepressant treatment of adequate dose and duration. In particular, although partial response appears to occur in 12% to 15% of the depressed patients studied, nonresponse is observed in 19% to 34% of this population. The prevalence of treatment-resistant depression derived from studies using ITT analysis is likely to be an overestimate of the actual occurrence of the phenomenon, as these rates also
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Address reprint requests to Maurizio Fava, MD, Clinical Psychopharmacology Unit, Massachusetts General Hospital, 15 Parkman Street WAC 815, Boston, MA 02114
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From the Depression Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts