Can't open the PDF? Click here for help.
Vol. 22, No. 4 / November 2010
IntroductionPhilip G. Janicak, MD
Rush University Medical Center, Chicago, IllinoisContinue to article
The World Health Organization (WHO) estimates that major depression will be the leading cause of disability by the year 2020.1 Based on data from the National Comorbidity Survey Replication, it is estimated that each year approximately 14 million adults in the United States experience a major depressive episode.2 Further, only about half receive a proper diagnosis and less than half adequately benefit from existing first-line therapies (eg, psychotherapy; antidepressant medication).
Results from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study provide insight into several important issues clinicians struggle with in managing these patients.3 For example, the primary endpoint chosen by investigators of this landmark National Institute of Mental Health-sponsored trial was remission (ie, minimal to absent symptoms with treatment). The distinction between remission and response is crucial: response often leaves patients with substantial residual symptoms and is more likely to culminate in relapse or recurrence in the months after an acute treatment episode.4
Another important observation was that as the number of treatment trials required increased, the chances of achieving remission diminished, and the likelihood of discontinuing treatment because of adverse events increased steadily.5 Further, as the number of trials needed to achieve remission increased, the risk of relapse rose and the time to relapse shortened.5 In the second phase of STAR*D, switching or augmenting produced remission in only an additional 25% of patients who did not adequately benefit from an initial aggressive trial of citalopram.6-8
What options are available to clinicians for patients with major depression who do not adequately benefit from standard initial treatments? Presently, if a patient is not adequately responsive to or cannot tolerate a first-line antidepressant trial (eg, selective serotonin reuptake inhibitor monotherapy), there are limited FDA-approved options—second-generation antipsychotic (SGA) augmentation or transcranial magnetic stimulation (TMS)—and several approaches supported by clinical studies and experience, such as switching to an alternate antidepressant or augmentation with a second antidepressant. Ironically, the two FDA-approved options were not included in STAR*D because at the time SGA augmentation was not a recognized viable approach and TMS was not yet clinically available.
The disappointing remission rates (approximately 25% to 30%) achieved in both the first and second phases of STAR*D, coupled with the substantial drop off in both the subsequent chances of remission and attenuated durability of effect, argue for an earlier consideration of SGA augmentation or TMS. In this context, the approved indication for TMS is in patients who fail one adequate antidepressant trial during the current episode. Although studies of aripiprazole, quetiapine, and olanzapine augmentation demonstrated efficacy, these agents carry substantial safety and tolerability concerns (eg, neuro-motor symptoms; weight and metabolic complications). By contrast, the efficacy and excellent safety and tolerability of TMS argue for its earlier introduction.9,10 Presently, a variety of factors—such as cost, adverse effects with SGAs, and limited clinical experience with TMS—usually relegate these therapies to third- or fourth-line strategies in most treatment settings.
Dr. Janicak receives research/grant support from and is consultant to and speaker for Bristol-Myers Squibb/Otsuka and Neuronetics, Inc.
Annals of Clinical Psychiatry ©2010 Quadrant HealthCom Inc.