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1.
Major depressive disorder (MDD) is a prevalent, chronic, medical disorder that encompasses a broad constellation of symptoms. The salience of painful physical symptoms in depressive presentations is increasingly appreciated. Duloxetine is a novel, potent, balanced, dual monoamine reuptake-inhibitor antidepressant indicated for the symptomatic relief of MDD. Duloxetine is marketed as an antidepressant that has inherent analgesic properties for depressed patients who present with prominent painful physical symptoms. Taken together, available evidence indicates that duloxetine provides a higher probability of, and shorter time to, remission than some antidepressants (e.g., fluoxetine). Duloxetine also offers symptom relief for painful physical symptoms in depressed patients. Pharmacoeconomic and cost-impact modelling analyses should be reformulated to consider duloxetine’s sym-ptom-alleviating effect on the somatic dimension of depressive illness.  相似文献   

2.
Major depressive disorder (MDD) poses a significant health problem and is estimated to be the third most costly and disabling disorder in the United States. Pharmacotherapy of depression has been successful, but improvements in response rates, remission rates, side effects, compliance and faster onset of therapeutic action have become prime objectives in drug development. There is considerable support for the hypothesis that dysfunctional serotonergic or noradrenergic neurotransmission may be etiological in depressed patients. Duloxetine is a balanced and potent reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE) being studied as an antidepressant medication. In this review, we highlight the preclinical pharmacology, pharmacokinetic profile, and effects of duloxetine in the pharmacotherapy of depression. Evidence for 5-HT and NE reuptake inhibition by duloxetine comes from in vitro and in vivo transporter binding and functional uptake studies. Taken together with efficacy data from in vivo microdialysis, electrophysiological and behavioral studies, it is evident that duloxetine is balanced as a dual serotonin norepinephrine uptake inhibitor in vivo. The clinical efficacy and safety of duloxetine in the treatment of MDD has been studied in 6 multicenter, randomized, double-blind, placebo-controlled trials. In these studies, duloxetine was found to be effective in the treatment of emotional/psychological and painful physical symptoms associated with depression. More importantly, duloxetine appears to have better response rates and remission from depressive symptoms, perhaps due to its ability to treat a wider range of symptoms.  相似文献   

3.
Abstract

Objective:

Painful physical symptoms are common in patients with major depressive disorder (MDD) and can negatively affect patient outcomes. Duloxetine has demonstrated efficacy in treating MDD and other certain painful conditions; this study specifically evaluated patients with both MDD and MDD-associated pain.  相似文献   

4.
Abstract

Objective:

Painful physical symptoms are common in patients with major depressive disorder (MDD) and may predict poorer treatment outcomes. Duloxetine has demonstrated efficacy in treating both MDD and certain other painful conditions. This randomized, double-blind clinical trial assessed the effects of duloxetine in patients with both MDD and MDD-associated physical pain.  相似文献   

5.
Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology.  相似文献   

6.
Frampton JE  Plosker GL 《CNS drugs》2007,21(7):581-609
Duloxetine (Cymbalta) is an orally administered, selective serotonin and noradrenaline reuptake inhibitor (SNRI) that has been approved for the treatment of major depressive disorder (MDD).Based on a considerable body of evidence, duloxetine at dosages ranging from 40 to 120 mg/day was effective in the short- and long-term treatment of MDD. Significant improvements versus placebo in core emotional symptoms as well as painful physical symptoms associated with depression, were seen in most, but not all, appropriately designed studies; results of meta-analyses suggested that improvements in these efficacy measures were apparent after 1-2 weeks' treatment with the highest recommended dosage of 60 mg once daily. Short-term (< or =15 weeks) administration of duloxetine at fixed or flexible dosages between 60 and 120 mg/day was noninferior to paroxetine 20 mg once daily, noninferior or inferior to escitalopram 10-20mg once daily, and had a similar global benefit-risk (GBR) profile to that of venlafaxine extended-release (XR) 150-225 mg/day in the treatment of MDD. Longer-term (6-8 months) treatment with duloxetine was similar in efficacy to paroxetine and escitalopram. Duloxetine is generally well tolerated, although it may be appropriate to avoid initiating treatment with the 60 mg/day dosage, as this has been associated with a higher discontinuation rate due to adverse events in some (but not all) comparative studies with escitalopram and venlafaxine XR.Definitive comparisons are awaited, although duloxetine seemingly provides a useful alternative to SSRIs and other SNRIs for the treatment of MDD. It also appears to be an attractive option for MDD patients presenting with painful physical symptoms.  相似文献   

7.
Double-blind, placebo-controlled clinical trials have evaluated and demonstrated the efficacy of duloxetine as an antidepressant in patients with major depressive disorders. The drug has been noted to be well tolerated and effective in the control of depressive symptoms. In addition, duloxetine has been shown to be better than placebo and as effective as paroxetine as an antidepressant and also better than placebo for reducing pain in both experimental models and patients. Duloxetine is a safe and well-tolerated new treatment option for depression including anxiety and painful physical symptoms. Furthermore, duloxetine has proven robust efficacy in stress urinary incontinence.  相似文献   

8.
A number of different antidepressants, each with unique pharmacological profiles, are used for treatment of major depressive disorder (MDD); however, these drugs have been found in placebo-controlled, large practical clinical trials to have limited efficacy for achieving full recovery in MDD patients. In particular, when depressed patients have pain symptoms, their chance of remission is significantly decreased. Pain also often leads to residual symptoms and incomplete functional recovery. Hence, while pain should be a principal target symptom in patients with MDD, there continues to be unmet need for pain treatment in depressed patients. Therefore, more diverse options for treatment approaches can be expected to enhance outcomes in clinical treatment of depressed patients with comorbid pain. In this context, Dr. Romera and colleagues have investigated an early antidepressant-switching strategy in patients with initial treatment failure. They found that early switching to a different antidepressant in MDD patients with moderate-to-severe symptoms of physical pain seems to lead to better pain and functional outcomes. This article discusses clinical significance, practical issues, potential limitations, and future research implications based on the findings from Dr. Romera and colleagues' study.  相似文献   

9.
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.  相似文献   

10.
Major depressive disorder (MDD) is one of the most common mental disorders, with a lifetime prevalence of approximately 13% in Europe. Although the primary symptom of MDD is depressed mood and a loss of interest or pleasure in everyday life, patients with MDD often present with a variety of other symptoms, such as sleep disturbances, fatigue, anxiety and somatic complaints. Antidepressant drugs are frequently used as first-line therapy for MDD. Bupropion is a second-generation antidepressant drug that inhibits reuptake of the neurotransmitters dopamine and norepinephrine, and has no direct serotonergic effects, a unique property among antidepressants. This article highlights the use of bupropion in the treatment of three patients with varying presentations of MDD, including as combination therapy in a patient refractory to treatment with a selective serotonin reuptake inhibitor, monotherapy in a patient with somatic symptoms of depression and loss of libido, and in a patient complaining of anxiety as a symptom of MDD. Bupropion treatment was successful in all patients, resulting in remission of symptoms and the patients returning to their normal lives.  相似文献   

11.
The evidence that the effects of the antidepressant duloxetine on painful physical symptoms in depression and chronic pain disorders are a direct analgesic effect rather than an indirect antidepressant effect is reviewed. Data from placebo-controlled acute studies of duloxetine in major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia syndrome are included in this review. In placebo-controlled studies of duloxetine in patients with major depressive disorder, non-depressed diabetic peripheral neuropathic pain, and fibromyalgia syndrome, duloxetine has a statistically significantly greater effect on pain than placebo. Path analysis suggests that in these patient populations, approximately 50, 90, and 80%, respectively, of the observed effect on pain is a direct analgesic effect rather than an indirect antidepressant effect. In fibromyalgia syndrome studies, duloxetine had similar and substantial effects on pain regardless of whether patients had comorbid major depressive disorder. Pain is a complex experience, involving both the physiological responses of the nociceptive system and the processing of that information in brain regions associated with emotion. While some effects of duloxetine on painful symptoms can be accounted for by its antidepressant action, the data strongly suggest that duloxetine also exerts a substantial direct analgesic effect over and above its antidepressant effects, in patients with major depressive disorder, diabetic peripheral neuropathic pain, and fibromyalgia syndrome.  相似文献   

12.
度洛西汀治疗疼痛的研究进展   总被引:1,自引:0,他引:1  
度洛西汀是第1个被美国FDA批准同时用于重症抑郁障碍和糖尿病周围神经病理性疼痛的药物,有证据表明度洛西汀的镇痛作用较强,并独立于其抗抑郁作用,病人对该药的耐受性较好,因此在慢性疼痛治疗方面有较好的应用前景。本文对度洛西汀在疼痛治疗方面的研究进展作一综述。  相似文献   

13.
Despite the advances of recent decades, there is still an urgent need for antidepressants with improved efficacy, safety and tolerability. Agomelatine is a new antidepressant with an innovative pharmacological profile. It is the first melatonergic antidepressant, and is a potent agonist of melatonin receptors (MT1 and MT2) with 5-HT2C antagonist properties. The efficacy of 25 mg/day agomelatine in treating major depressive disorder (MDD) has been demonstrated in a number of placebo-controlled studies. Evidence of improvement in depressive symptoms was observed in a dose-ranging study in which 25 mg/day agomelatine was significantly better than placebo, whatever the rating scale used (Hamilton Rating Scale for Depression, Clinical Global Impression, and Montgomery-Asberg Depression Rating Scale). These results have been confirmed in two similarly designed placebo-controlled studies. Agomelatine also produces a significant improvement in anxiety compared to placebo, according to Hamilton Rating Scale for Anxiety scores. The efficacy of agomelatine has been studied in subpopulations with more severe depression, demonstrating its efficacy in these difficult-to-treat patients. In view of the available data on agomelatine, this antidepressant can be regarded as an innovative treatment for MDD patients, offering a new approach in the management of depressed patients.  相似文献   

14.
CONTEXT: Major depressive disorder causes significant morbidity and mortality. Current therapies fail to fully treat both emotional and physical symptoms of major depressive disorder. OBJECTIVE: To evaluate duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, on improvement of emotional and painful physical symptoms. DESIGN: Randomized, double-blind, evaluation of duloxetine at 40 mg/d (20 mg twice daily) and 80 mg/d (40 mg twice daily) versus placebo and paroxetine 20 mg/d in depressed outpatients. MAIN OUTCOME MEASURES: The primary efficacy measure was the 17-item Hamilton Depression Rating Scale. Visual Analog Scales for pain, Clinical Global Impression of Severity, Patient's Global Impression of Improvement, and Quality of Life in Depression Scale were also used. Safety was evaluated by assessing discontinuation rates, adverse event rates, vital signs, and laboratory tests. RESULTS: Duloxetine 80 mg/d was superior to placebo on mean 17-item Hamilton Depression Rating Scale total change by 3.62 points (95% CI 1.38, 5.86; P = 0.002). Duloxetine at 40 mg/d was also significantly superior to placebo by 2.43 points (95% CI 0.19, 4.66; P = 0.034), while paroxetine was not (1.51 points; 95% CI -0.55, 3.56; P = 0.150). Duloxetine 80 mg/d was superior to placebo for most other measures, including overall pain severity, and was superior to paroxetine on 17-item Hamilton Depression Rating Scale improvement (by 2.39 points; 95% CI 0.14, 4.65; P = 0.037) and estimated probability of remission (57% for duloxetine 80 mg/d, 34% for paroxetine; P = 0.022). The only adverse event reported significantly more frequently for duloxetine 80 mg/d than for paroxetine was insomnia (19.8% for duloxetine 80 mg/d, 8.0% for paroxetine; P = 0.031). Hypertension incidence was not affected by any treatment. CONCLUSION: Duloxetine therapy was efficacious for emotional and physical symptoms of depression, with a selective serotonin reuptake inhibitor-like profile of side effects.  相似文献   

15.
Over 75% of depressed patients in primary care complain of painful physical symptoms such as headache, stomach pain, neck and back pain as well as non-specific generalized pain. The presence of such symptoms predicts a greater severity and a less favourable outcome of depression with a poorer health-related quality of life. World Health Organization data obtained in primary care centres worldwide show that 22% of all primary care patients suffer from persistent debilitating pain and that these patients are four times more likely to have co-morbid anxiety or depressive disorder than pain-free primary care patients. Not unexpectedly, the risk of depression is greater when the pain is more diffuse, as indicated by the number of painful sites, and has a greater effect on the quality of life. Certain depressive symptoms, such as low energy and sleep disturbances, are commonly found in patients with co-morbid pain, whereas the opposite is true for symptoms such as guilt and loneliness. Increasingly, major depression is seen as being composed of psychological, somatic and painful physical symptoms. In order to achieve full sustained remission it is necessary to treat symptoms in all three of these areas. The area of painful physical symptoms is unfortunately still poorly understood and clearly merits greater attention.  相似文献   

16.
INTRODUCTION: Affective disorders, including major depressive disorder (MDD), are among the most severely disabling mental disorders, and in many cases are associated with poor treatment outcomes. From the emergence of the monoamine hypothesis of depression, the first-line treatment for MDD had mainly acted by inhibiting monoamine reuptake, and thereby increasing these levels in the synaptic cleft. However, in recent years, several new antidepressant drugs have appeared, including duloxetine, a dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor recommended for the treatment of MDD. AREAS COVERED: The article reviews and discusses the biochemical and functional profile of duloxetine splitting the review into acute and long-term treatment with this dual monoamine reuptake inhibitor. In addition, the authors summarize available preclinical behavioral research data, which have demonstrated among other effects, the antidepressant-like activity of duloxetine in several animal models. The authors focus on the most recent literature on synaptic neuroplasticity modulation of this antidepressant drug. Finally, the authors briefly mention other approved indications of duloxetine. EXPERT OPINION: Duloxetine inhibits 5-HT and NA reuptake, effectively desensitizes various autoreceptors and promotes neuroplasticity. Clinically, duloxetine is an effective antidepressant that is well tolerated and has significant efficacy in the treatment of MDD.  相似文献   

17.
Duloxetine, an inhibitor of serotonin and norepinephrine reuptake, has been approved for the treatment of major depressive disorder. In this analysis, data from eight, double-blind, placebo-controlled duloxetine trials were pooled, and the response to duloxetine treatment (40-120 mg/day) was compared between patients experiencing their first episode of depression (n=581) or a subsequent episode (n=1321), and between patients experiencing a depressive episode of short (n=596), medium (n=669), or long (n=649) duration based on tertile divisions. Treatment response was determined on the basis of changes from baseline in the 17-item Hamilton Rating Scale for Depression total score, the Clinical Global Impressions of Severity Scale, and painful physical symptoms (Somatic Symptom Inventory and Visual Analog Scales). Overall, changes on all outcome measures and response and remission rates were significantly greater in duloxetine-treated patients than in placebo-treated patients. Furthermore, the effect of duloxetine was similar across all episode characteristic groups (first/subsequent episode, short/medium/long episode duration). Only for the Somatic Symptom Inventory was the effect of duloxetine significantly different between groups (greater in the subsequent episode group than in the first episode group). Duloxetine was effective in the treatment of first and subsequent episodes of major depressive disorder, and regardless of duration of the current depressive episode.  相似文献   

18.
It is the standard practice in antidepressant efficacy trials (AETs) to exclude potential participants with major depressive disorder (MDD) who score below a threshold on the Hamilton Rating Scale for Depression (HAM-D). It is unknown to what extent various cutoff scores impact on the generalizability of these trials. In the present report, we sought to determine how many patients with MDD presenting to an outpatient practice would fail to qualify for an AET because their symptoms were not sufficiently severe, and to what extent the variability in HAM-D cutoff scores impacts exclusion rates. Fifteen hundred individuals presenting for an intake at a psychiatric outpatient practice underwent an evaluation with semistructured diagnostic interviews. Five hundred and three patients received a principal diagnosis of nonbipolar, nonpsychotic MDD. Thirty-nine AETs published in five leading journals during the past 7 years were reviewed, 36 of which required a minimum score on the HAM-D for inclusion. We applied the HAM-D cutoffs used in these AETs to the 503 depressed patients to determine how many would qualify for each AET. Based on the least and most restrictive cutoff scores, between 11.3% and 71.0% of the depressed patients from our practice had an insufficient HAM-D score to qualify for an AET. The two most commonly used cutoff scores would lead to the exclusion of almost half of our sample. AETs tend to include the subset of depressed individuals with moderate to severe MDD and exclude a significant proportion of depressed patients who have mild MDD. The implications of these findings are discussed.  相似文献   

19.
BACKGROUND: Major depressive disorders (MDD) present a significant public health problem, in terms of burden for individual sufferers, their families and society as a whole. Recently, dualacting antidepressants, which block both serotonin (5-HT) and noradrenaline (NA) reuptake, have been developed with the hope of improving depression treatment outcomes. Duloxetine is a dual reuptake inhibitor of 5-HT and NA that has recently been licensed in the USA for the treatment of MDD. OBJECTIVE: This paper summarises efficacy and tolerability data for duloxetine with particular reference to the dose recommended for clinical use -- 60 mg once daily. Papers relating to duloxetine 60 mg once daily were identified through Medline searches and the publication databases at Eli Lilly/Boehringer Ingelheim. FINDINGS: Randomised, placebo-controlled studies have demonstrated the efficacy of duloxetine 60 mg once daily for the treatment of depression in the short and long term. Thus, duloxetine 60 mg once daily was superior to placebo in reducing once daily was superior to placebo in reducing MDD symptoms according to the primary efficacy MDD symptoms according to the primary efficacy measure -- the 17-item Hamilton Depression Rating Scale (HAMD(17)). Significantly greater improvements in subfactors of HAMD(17) and quality of life measures were also seen. In addition, duloxetine has been shown significantly to reduce the general aches and pains that frequently accompany MDD. A recent placebo-controlled study demonstrated that duloxetine improved cognition and depression measures in depressed elderly patients. Duloxetine appears to have an acceptable tolerance. The most frequently observed adverse events with duloxetine were nausea, dry mouth and somnolence. Importantly, duloxetine did not appear to have a clinically significant effect on blood pressure. CONCLUSION: In summary, duloxetine 60 mg once daily is effective for the treatment of core depressive symptoms, as well as general aches and pains associated with depression.  相似文献   

20.
The mammalian hippocampus continues to generate new neurons throughout life. The function of adult-generated neurons remains controversial, but adult neurogenesis in the hippocampus is related to depression. Studies show that neurogenesis in the hippocampus is regulated by antidepressants in both humans and rodents, but no studies have examined the effects of age, sex, or antipsychotic exposure on the relationship between depression, antidepressant exposure, and hippocampal neurogenesis in humans. Hippocampal sections were obtained from the Stanley Medical Research Institute and were immunohistochemically labeled for the immature neuron marker doublecortin and the cell cycle arrest marker p21. We compared the number of cells in the granule cell layer and subgranular zone that expressed these proteins in brains from control subjects (n=12), patients with major depressive disorder (MDD) without psychotic symptoms (n=12), and patients with MDD and psychotic symptoms (n=12). We show here that the density of doublecortin/NeuN expression was increased in MDD patients compared with controls and MDD patients with psychosis, with the effect greater in women. Further, we show that older depressed patients without psychosis had higher levels of p21/NeuN expression and that depressed individuals prescribed antidepressants had higher levels of p21/NeuN expression, but only in older women. We show for the first time that changes in neurogenesis due to prescribed antidepressants or depression are dependent on age, sex, and the presence of antipsychotics or psychotic symptoms.  相似文献   

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