Serotonin and noradrenaline involvement in urinary incontinence, depression and pain: scientific basis for overlapping clinical efficacy from a single drug, duloxetine

Aims: Serotonin (5-HT) and noradrenaline (NA) are important monoamine neurotransmitters that are ubiquitously distributed throughout the peripheral and central nervous system and modulate functions that are vital to survive. Both neurotransmitters may be involved in the pathophysiological process or the treatment of - at first glance - divergent disease areas, namely stress urinary incontinence, major depressive disorder and neuropathic pain. The present review aims at describing the neurophysiological similarities between these disease areas, focussing on the role of the neurotransmitters 5-HT and NA at synapses of the spinal and supraspinal neural circuitry. Results/discussion: Recent clinical studies show convergence of symptoms (i.e. comorbidity) for incontinence, depression and pain, suggesting common biochemical imbalances. Duloxetine, a dual serotonin and noradrenaline reuptake inhibitor, has a central mechanism of action at different locations in the central nervous system and has proven to be a sound treatment of all these different diseases. Data obtained from animal model studies, randomised placebo-controlled clinical trials, as well as open label trials have provided evidence of the efficacy and safety of duloxetine as a suitable compound for the treatment of stress urinary incontinence in women as well as major depressive disorder and diabetic neuropathic pain in both men and women.