Treatment Resistant Depression Overview

Major depression has become a health crisis of epidemic proportions in the modern world. Unfortunately, up to one third of patients with depression fail to achieve remission despite multiple trials of pharmacologic agents of differing classes in the presence or absence of conventional augmentation strategies. (1)

The risks of not responding to (or tolerating) treatment have been highlighted by recent studies documenting that partial—but incomplete—response is associated with an increased risk of full symptomatic relapse (even when on therapy) and a worse long term disease course, as well as with significantly impaired quality of life. Treatment resistance also results in a six times increase in direct health care costs. These factors highlight the tremendous need to identify novel treatment strategies, especially for depressed patients who are unresponsive to conventional therapies

One possible mechanism that may contribute to treatment resistance is increased production and release of chemicals from the immune system called proinflammatory cytokines. These chemicals mediate the body’s response to infectious agents like bacteria and have been shown to be increased by psychological stress. By acting on the brain, these cytokines also produce the symptoms that we associate with being sick, including fever, malaise and changes in sleep and appetite. Several lines of evidence indicate that proinflammatory cytokines may contribute to the development of major depression and may thus represent a novel target for the pharmacological treatment of the disorder.

To test this possibility, we are conducting this study to determine if the TNF-alpha antagonist, infliximab (Remicade®), is more effective than placebo in reducing symptoms of depression in patients who have not responded to, or been unable to tolerate, at least two previous treatments in the current depressive episode. Patients must also have evidence of increased proinflammatory cytokines as reflected by the presence of increased blood levels of c-reactive protein (CRP), a protein released by the liver in response to proinflammatory cytokines.

1. Greden JF. The burden of disease for treatment-resistant depression. Journal of Clinical Psychiatry. 2001;62 Suppl 16:26-31.