Substance P (SP) is possibly involved in the etiopathology of affective disorders. Here we investigated the relationship of SP serum levels and response to antidepressant drug therapy. SP serum levels were determined before and during a 9-week drug trial in 40 depressed patients treated with paroxetine in combination with either lamotrigine (n = 20) or placebo (n = 20). Responders (n = 18) and non-responders (n = 22) significantly differed in SP serum levels: responders started with higher SP levels that decreased during drug therapy, whereas non-responders had lower SP levels that increased at the beginning. There were no differences between patients with adjunct lamotrigine or placebo. These preliminary data indicate that SP serum levels might be related to response to antidepressant drug therapy. Further studies have to substantiate this finding.
Preclinical investigations suggest that the neuropeptide substance P might be involved in the etiopathology of pain, depression, and anxiety. In a recent study, the substance P receptor antagonist MK-869 showed antidepressant and anxiolytic activity in depressed outpatients which was comparable to a standard SSRI. The MK-869 was well tolerated. Although these findings are promising, further studies are necessary to prove the hypothesis that substance P receptor antagonists represent a new class of antidepressants or anxiolytics. Respective studies are currently underway.
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