(PSYCHIATRIC TIMES) - The management of treatment-resistant depression (TRD) remains a vexing clinical problem for a large population of patients and their clinicians. An estimated 32 to 35 million adults in the United States experience an episode of major depression during their lifetime.1 When depressed patients present for treatment, the results are often less than satisfactory. Even under the relatively ideal treatment conditions of the recent NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, only 32.9% of patients achieved remission in level 1 with citalopram.2 An analysis of 36 open and double-blind antidepressant trials found a 36% rate of partial response or nonresponse.3 About 15% of patients had depression that failed to respond to multiple treatment trials.4 Depressed patients report impaired function and they overuse medical services.5,6
Patients with TRD may represent a biologically unique subtype of depressed persons.7 Unfortunately, the longer a patient remains depressed, the lower his or her chance of recovery—a fact that lends a sense of urgency to finding appropriate therapy.8
This article focuses on recent innovations in diagnostic issues, tactics, and strategy, and takes a brief look at the future.
Defining treatment resistance
The lack of consensus about how to define treatment resistance and how it should be classified are major methodological problems.4,9,10 The term “treatment resistance” obviously implies an inadequate response to antidepressant therapy. Sackheim9 notes that 4 of the following conditions must be met before the adequacy of an antidepressant trial can be judged:
* Drug dosage was titrated to the maximum when appropriate.
* The drug was administrated for an adequate duration and at maximal dosage as appropriate.
* The adequacy of patient adherence to therapy was monitored.
* The degree of nonresponse (partial vs complete) was recorded.
Without such detail, one cannot be certain that patients are not pseudo- resistant (ie, inappropriately classified as having TRD, when the real issue is suboptimal treatment). Up to half of treatment nonresponse may be a result of poor adherence to medication regimens and/or poor tolerability.11
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