Summary and Introduction
Summary
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.
Introduction
The use of a single drug for multiple indications is increasingly common, particularly in primary care. Duloxetine hydrochloride, a relatively balanced serotonin and noradrenaline reuptake inhibitor (SNRI), has been studied extensively for the treatment of female stress urinary incontinence (SUI), major depressive disorder (MDD) and diabetic peripheral neuropathic pain (DPNP) and is the first and only SNRI approved in varying countries to treat these indications.
Recent studies from both the psychiatric and gynaecological disciplines indicate that there is significant overlap of incontinence and pain symptoms in patients with MDD, especially in women with moderate or severe incontinence and in those with urge incontinence and overactive bladder (OAB). Similarly, the concurrent presentation of symptoms of pain and depression is fairly common. At first glance, a common neurobiological underpinning for three disparate medical conditions, such as incontinence, depression and pain, may seem incredible. However, serotonin (5-HT) and noradrenaline (NA) are important monoamine neurotransmitters that are ubiquitously distributed throughout the peripheral and central nervous system (CNS) and coordinate a plethora of somatic and visceral responses to various psychological states produced by changes in perceived environmental conditions, especially those involving fight-or-flight responses or other stressful conditions.