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Anti-TNF-α Compounds as a Treatment for Depression

Several clinical trials attested for the antidepressant efficacy of anti-TNF-α compounds (in patients with medical illnesses, major depression, or bipolar depression) [70]. Selective TNF-α antagonists such as infliximab and etanercept showed favorable neurological/antidepressant effects in specific sub-groups of patients. However, it is important to emphasize that most of the available data regarding the antidepressant effects of selective TNF-α antagonists is derived from studies in non-psychiatric patients (i.e., patients with inflammatory-associated diseases who presented depressive symptoms). Moreover, some evidence suggests that there is no connection between anti-TNF-α therapy and improvement in mood symptoms [139,150,151]. Therefore, new randomized, placebo-controlled clinical trials are necessary for direct examination of the mood-modulating effects of TNF-α antagonists in patients with mood disorders. In this regard, recently, concerns have been raised regarding the efficacy of selective TNF-α antagonists as a therapeutic strategy for mood disorders [139,151,189,190]. It is important to mention that most clinically available anti-TNF-α compounds possess low-to-null ability to cross the BBB, mainly due to their large molecular weight [191,192,193]. This suggests that the reported beneficial behavioral (antidepressant) effects of these compounds are derived from peripheral inhibition of TNF-α activity rather than a direct effect on the brain. Potent peripheral inhibition of TNF-α activity may be sufficient for diminishing brain inflammation. Therefore, it is important to continue studying the therapeutic mechanism of action and effectiveness of selective TNF-α antagonists as a treatment for mood disorders.

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