Duloxetine: a dual serotonin-norepinephrine reuptake inhibitor for treatment of major depressive disorder.
ABSTRACT The burden of mental illness has been underestimated worldwide. Depression was the fourth leading cause of disease burden in the world in 1990 and is projected to be the second leading cause of disability by 2020. It is a leading cause of morbidity and mortality in the United States, costing billions of dollars annually in direct and indirect medical costs and losses in productivity. Patients with major depressive disorder (MDD) may experience both psychological and medical complaints, including somatic sensations or pain. Some antidepressants have been shown to treat chronic pain syndromes, but despite the variety of antidepressants available in the United States, only 65-70% of patients respond to initial antidepressant treatment. Treatments are limited by delayed onset of antidepressant effects, side effects, partial response, and treatment resistance. Duloxetine, approved by the U.S. Food and Drug Administration for the treatment of MDD, is a reuptake inhibitor at serotonergic and noradrenergic neurons and appears to have low affinity for other neurotransmitter systems. In clinical trials, duloxetine was effective for the treatment of MDD and was well tolerated. Further study is needed to compare its efficacy with that of other antidepressants, to clarify effects on somatic symptoms, and to assess potential adverse cardiovascular and sexual side effects. Duloxetine is also approved for the management of diabetic peripheral neuropathic pain and is under investigation for the treatment of stress urinary incontinence in women.
- [Show abstract] [Hide abstract]
ABSTRACT: Burning mouth syndrome (BMS) is a condition accompanied by oral burning symptoms, including glossal pain (glossodynia) without a detectable cause. Although BMS is a chronic-pain syndrome, only one self-controlled pilot study and some case reports have reported that milnacipran is effective for the treatment of chronic pain, including that caused by BMS. However, these papers assessed only pain, and the dosage of prescribed milnacipran varied from 30 to 150 mg/d in each patient. In this study, the dosage of prescribed milnacipran was set at 60 mg/d for 12 weeks for all patients, and depression and quality of life (QOL) were assessed in addition to pain. Twelve patients with glossodynia participated in this study. Milnacipran was initiated at a dosage of 15 mg/d and then raised gradually to 60 mg/d after 4 weeks of treatment; this dose was continued until the end of the study (total of 12 weeks). The evaluation included the Hamilton Rating Scale for Depression, the Visual Analog Scale score for pain evaluation, the General Oral Health Assessment Index for oral-related QOL evaluation, and the Medical Outcomes Study's 36-Item Short-Form Health Survey (SF-36) for whole QOL evaluation. The Hamilton Rating Scale for Depression score decreased significantly after treatment with a 60-mg/d dosage of milnacipran for 12 weeks. However, the Visual Analog Scale pain, General Oral Health Assessment Index, and SF-36 scores did not change. A randomized, double-blind, placebo-controlled multi-institution trial of milnacipran will be essential to determine its effectiveness for the treatment of BMS.Clinical neuropharmacology 01/2011; 34(4):170-3. · 1.84 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background The noradrenergic system contributes to pain modulation, but the roles of its specific adrenoceptors are still being defined. We have identified a novel, potent (rat EC50 = 4.3 nM) and selective α2B receptor agonist, A-1262543, to further explore this adrenoceptor subtype's contribution to pathological nociception.Methods Systemic administration of A-1262543 (1–10 mg/kg, intraperitoneal) dose-dependently attenuated mechanical allodynia in animals with a spinal nerve ligation injury. To further explore its mechanism of action, the activity of nociceptive neurones in the spinal cord and medial prefrontal cortex (mPFC) were examined after injection of 3 mg/kg of A-1262543 (intravenous, i.v.). These effects were compared with duloxetine (3 mg/kg, i.v.), a dual noradrenaline (NA) and serotonin (5-HT) reuptake inhibitor.ResultsSystemic administration of A-1262543 or duloxetine did not alter the spontaneous or evoked firing of spinal wide dynamic range and nociceptive-specific neurones in the neuropathic rats, indicating that neither compound engaged spinal, peripheral or descending pathways. In contrast to the lack of effect on spinal neurones, both A-1262543 and duloxetine reduced the evoked and spontaneous firing of ‘pain-responsive’ (PR) neurones in the mPFC. Duloxetine, but not A-1262543, also inhibited the firing of pain non-responsive (nPR) neurones in the mPFC probably reflecting duloxetine's contribution to modulating non-pain endpoints.Conclusions These data highlight that activation of the α2B adrenoceptor as well as inhibiting NA and 5-HT reuptake can result in modulating the ascending nociceptive system, and in particular, dampening the firing of PR neurones in the mPFC.European journal of pain (London, England) 09/2014; · 3.37 Impact Factor
- Disease-a-month: DM 01/2014; 60(1):6-47. · 1.57 Impact Factor