5-HT1A receptor antagonists as putative adjuvants to antidepressants: preclinical and clinical evidence.
Recently, the hypothesis was advanced that addition of a serotonin 1A (5-HT1A) receptor antagonist may shorten the latency to antidepressant action of selective serotonin reuptake inhibitors (SSRIs) as well as increase their efficacy in the treatment of depression. This hypothesis is based on preclinical findings showing that the purported increase in 5-HT concentrations in terminal regions produced by acute administration of SSRIs is hampered by a concomitant increase in 5-HT levels in cell body area leading to decreased serotonergic cell firing due to increased stimulation of inhibitory 5-HT1A autoreceptors. In this review data are presented showing that adding a 5-HT1A receptor antagonist prevents this feedback inhibition of serotonergic cell firing and allows more 5-HT to be released. The hypothesis is supported by clinical data resulting from combining an SSRI with pindolol, which possesses 5-HT1A receptor antagonistic action.
Arborelius
L
L
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA. Lotta.Arborelius@fyfa.ki.se