The involvement of serotonergic mechanisms in acupuncture acceleration of the response to paroxetine in patients with major depressive disorder

Abstract

An apparent shortcoming of selective serotonin reuptake inhibitor (SSRI) therapy is the delay in the onset of the therapeutic action. This is largely because the initial SSRI treatment activates negative feedback through 5-HT1A autoreceptors endowed on the raphe 5-HT neurons, resulting in decrease in the net amount of extracullular 5-HT levels. Early studies have shown that electroacupuncture (EA) stimulation could directly activate the raphe 5-HT neurons and enhance neuronal firing. This has led to a hypothesis that EA might serve as an “accelerator” for SSRI therapy. To test this hypothesis, 28 patients with first-episode major depressive disorder (MDD) were randomized to receive paroxetine (PRX, 10-40 mg/day) combined with or without EA (n = 14 each) for 6 weeks and blood samples were collected at baseline and at week 2 for platelet 5-HT analysis. EA intervention was conducted on several cross-midline pairs of acupoints on scalp for 45 min daily. Patients having EA intervention displayed a significantly greater alleviation of depressive symptoms as early as at week 1, significantly higher clinical response at week 2-4 and remission rate at week 5 compared to patients without EA intervention (p < 0.05). Patients under EA intervention also showed a significantly higher plasma 5-HT level at week 2 (p = 0.009). Moreover, EA intervention for 2 weeks significantly reduced the expression of platelet 5-HT1A receptors compared to baseline (p < 0.001), whereas PRX treatment alone elevated the 5-HT1A expression (p = 0.002). These data suggest that EA intervention can accelerate the clinical response to SSIR treatment in depressed patients and this accelerative effect is associated with enhancement of 5-HT release and the suppression of 5-HT1A autoreceptors.