Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor that has been recently approved for the treatment of major depressive disorder (MDD). However, little is known about the relationship between DLX plasma levels and clinical response. The aims of this open-label study were 1) to assess clinical outcome and tolerability of DLX by means of clinician and patient assessments and 2) to evaluate the value of plasma DLX levels as predictors of clinical response and tolerability. This was a naturalistic, open-label study of 45 outpatients affected with MDD (16 men and 29 women), who received DLX at doses of 30-120 mg/day and were evaluated at baseline (T0) and after 2, 4 and 12 weeks (T1-3). The assessments included the Hamilton Rating Scales for Depression (HRSD) and Anxiety (HRSA), Clinical Global Impression-Severity (CGI-S), Beck's Depression Inventory (BDI) and a mood visual analogue scale (VAS). Compared with T0, there were significant improvements in HRSD at T1, T2 and T3 (P < 0.001), in HRSA, CGI-S and the self-administered BDI at T2 and T3 (P < 0.001), and in the VAS scores shown at T3 (P = 0.01). DLX treatment was safe and well tolerated. Plasma DLX levels at T2 ranged from 5 to 135 ng/mL (mean +/- SD = 53.56 +/- 39.45) and correlated almost significantly with the DLX dose (r = 0.35; P = 0.069). There was a significant curvilinear quadratic relationship between the improvement of HRSA scores and plasma DLX levels (R(2) = 0.27; P = 0.02). The incidence of anxiety or irritability was associated with the highest plasma levels. Our findings suggest that monitoring plasma DLX levels may be helpful in predicting better treatment responses and tolerability. The present data seem to suggest an optimal anxiolytic efficacy of DLX at intermediate plasma levels.
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PMID:Clinical outcome and tolerability of duloxetine in the treatment of major depressive disorder: a 12-week study with plasma levels. 1940 51

(1) Fibromyalgia is characterised by a range of symptoms that include muscle pain, fatigue and sleep disorders. Anxiety and depression are often also present. The cause is unknown. More women than men are affected; (2) The following review focuses on differential diagnoses and available treatments for fibromyalgia, based on a review of the literature using the standard Prescrire methodology; (3) Fibromyalgia is mainly diagnosed by excluding other possibilities. The principal differential diagnoses are rheumatic involvement of the spine, systemic inflammatory disorders, and hypothyroidism. Unlike these other conditions, fibromyalgia is not associated with radiological or laboratory abnormalities; (4) Paracetamol has not been compared with other treatments in fibromyalgia. Nonsteroidal antiinflammatory drugs have no specific effect; (5) The only two trials assessing tramadol showed little effect; in one study the average pain score was 53 mm in the tramadol group versus 65 mm in the placebo group, on a scale ranging from 0 to 100 mm. The adverse effects of tramadol are those of opiates in general, mainly nausea and dependence. Tramadol interacts with numerous other drugs; (6) The efficacy of tricyclic antidepressants is also difficult to quantify. Their limited superiority over placebo lasts no more than a few months. The efficacy of selective serotonin reuptake inhibitor antidepressants (fluoxetine, paroxetine and citalopram), serotonin and nonadrenaline reuptake inhibitors (duloxetine and milnacipran) is even less well established. Duloxetine has been tested in four placebo-controlled trials with unconvincing results; (7) Pregabalin and gabapentin, two antiepileptic drugs, appear to be more effective than placebo but have only been tested in short-term trials. In one trial 44% of patients in the pregabalin group said they felt better after 13 weeks versus 35% of patients in the placebo group. However, adverse effects are frequent and sometimes troublesome (drowsiness, dizziness, nausea, weight gain). In clinical trials, 19% to 33% of patients stopped treatment due to adverse effects after 13 weeks, depending on the dose of pregabalin; (8) Assessments of non-drug treatments in this setting are generally mediocre. The best-assessed alternative therapies (acupuncture and physical exercise) only have a limited effect; (9) In practice, when a patient presents with symptoms compatible with fibromyalgia, the first step is to rule out a treatable condition. Quality of life may be improved by first acknowledging that the pain is real, and possibly by providing psychological, medical, social and occupational support. The limited efficacy of available drugs, and their potential adverse effects, should be discussed with the patient.
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PMID:Fibromyalgia: poorly understood; treatments are disappointing. 1974 61

Duloxetine is a serotonin-noradrenaline reuptake inhibitor with established efficacy for the short-term treatment of major depressive disorder. Efficacy in continuation treatment (greater than six months of continuous treatment) has been established from both open and placebo-controlled relapse prevention and comparative studies. Seven published studies were available for review and showed that in both younger and older populations (aged more than 65 years) the acute efficacy of duloxetine was maintained for up to one year. Response to treatment was based on accepted criteria for remission of depression and in continuation studies remission rates were greater than 70%. Comparative studies showed that duloxetine was superior to placebo and comparable to paroxetine and escitalopram in relapse prevention. Importantly a study of duloxetine in patients prone to relapse of major depressive disorder showed that the medication was more effective than placebo in this difficult to treat population. Side effects of duloxetine during continuation treatment were predictable on the basis of the known pharmacology of the drug. In particular there were no significant life-threatening events which emerged with continued use of the medication. On the other hand vigilance is required since the data base on which to judge very rare events is limited by the relatively low exposure to the drug. Duloxetine has established both efficacy and safety for continuation treatment but its place as a first-line treatment of relapse prevention requires further experience. In particular further comparative studies against established agents would be useful in deciding the place of duloxetine in therapy.
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PMID:Continuation treatment of major depressive disorder: is there a case for duloxetine? 2036 4

Duloxetine, a dual acting norepinephrine serotonin reuptake inhibitor, is a relatively new pharmacologic agent utilized in the treatment of depression, as well as diabetic neuropathic pain, fibromyalgia, and female stress urinary incontinence. This expanding scope of usage will inevitably lead to its eventual appearance during routine post-mortem toxicologic assays. Currently there is a paucity of post-mortem toxicologic data concerning duloxetine. The current report provides six additional case reports of post-mortem duloxetine levels, along with a review of duloxetine's pharmacokinetics, and the toxicologic manifestations which have been reported in the literature. The post-mortem levels reported, including the highest level recorded to date, are integrated with previously published reports to generate a foundation for a nascent guide to the interpretation of post-mortem duloxetine levels that could be encountered during routine post-mortem toxicologic analyses, and establish a basis upon which the establishment of toxic and lethal thresholds for this compound can be further elucidated with greater clarity.
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PMID:Adverse events, toxicity and post-mortem data on duloxetine: case reports and literature survey. 2038 51

The pharmacological treatment of older adults with major depressive disorder presents a variety of challenges, including a relative lack of high quality studies designed to measure the efficacy and safety of antidepressants specific to this patient population. Gaining a clear understanding of how to use antidepressants in elderly patients with depression, especially new and widely used agents, would provide valuable insight to clinicians. The purpose of the current article is to review the pharmacology, efficacy and safety of newer antidepressants (i.e. escitalopram, duloxetine and desvenlafaxine) in the treatment of late-life depression. To accomplish this goal, a MEDLINE and PubMed search (1966 - February 2010) was conducted for relevant articles. Animal and human studies have clearly demonstrated the effects of desvenlafaxine, duloxetine and escitalopram on monoamine reuptake transporters. The serotonergic and noradrenergic actions of desvenlafaxine and duloxetine may provide for a faster onset of antidepressant activity in the elderly, but more definitive data are needed and the clinical effects of the possible faster onset of action need to be elucidated. Duloxetine and escitalopram are extensively metabolized via cytochrome P450 (CYP) enzymes and the decreased hepatic metabolism present in many older adults should be taken into account when prescribing these medications. Duloxetine possesses the greatest likelihood of producing clinically relevant drug-drug interactions because of its inhibition of CYP2D6. All three agents must also be used cautiously in older adults with poor renal function. In terms of clinical efficacy, 14 prospective published trials involving escitalopram (n = 8) and duloxetine (n = 6) in the treatment of older adults with major depressive disorder were identified. No such studies involving desvenlafaxine were found. Of the five randomized, double-blind, controlled trials, 46% and 37% of antidepressant-treated patients were considered responders and remitters, respectively. In contrast to escitalopram, duloxetine-treated patients experienced improvements in depressive symptoms that more consistently differentiated themselves from the symptoms of placebo-treated patients. Escitalopram and duloxetine were generally well tolerated, but 5-20% and 10-27% of patients, respectively, dropped out because of medication-related adverse effects. Adverse effects experienced by older adults were generally similar to those experienced by younger adults, although indirect comparisons suggest that older adults are more likely to experience dry mouth and constipation with duloxetine and escitalopram, while orthostasis may be more common in older adults prescribed desvenlafaxine. Overall, duloxetine and escitalopram represent modestly effective treatments for late-life depression that are generally well tolerated but do produce a variety of adverse effects. Conclusions regarding desvenlafaxine cannot be made at this time because of a lack of geriatric-specific data.
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PMID:Pharmacological and clinical profile of newer antidepressants: implications for the treatment of elderly patients. 2065 91

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.
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PMID:Effects of duloxetine treatment on brain response to painful stimulation in major depressive disorder. 2066 37

The objective of this prospective study was to assess the efficacy and tolerability of duloxetine in the treatment of in military veterans with posttraumatic stress disorder (PTSD).Twenty subjects were enrolled in this 12-week, open-label trial. Diagnosis and symptom severity were assessed with the Clinician Administered PTSD Scale (CAPS). Depressive symptoms were assessed the Hamilton Depression Rating Scale. All subjects had a CAPS score of at least 60 at baseline. Subjects with lifetime history of psychotic disorders or bipolar illness were excluded. Fifteen participants completed 12 weeks of treatment, five dropped-out from the trial, 3 due to side effects. For patients who discontinued, missing values were estimated using "the last observation carried forward" method. Significant improvements were seen on: CAPS total and all subscales, depression and sleep measures. Most of the improvement was observed by week 2 of treatment. Nine participants (45%) were classified as responders, defined by 20% or greater improvement on CAPS total score. The mean daily dose of duloxetine was 81 mg. The most common side effects were constipation (20%) diarrhea (25%) and nausea (20%). Two subjects developed tachycardia, one withdrew from the trial due to this problem. Duloxetine had a fast onset of action and was effective in about half of the subjects, it was well tolerated in most subjects. These preliminary results in a difficult to treat population warrant the conduction of a double blind, placebo-controlled study of duloxetine in PTSD.
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PMID:Duloxetine in military posttraumatic stress disorder. 2115 Aug 44

Fibromyalgia syndrome (FMS) is a widespread pain condition associated with a wide range of additional symptoms including fatigue, insomnia, depression, anxiety and stiffness. Duloxetine is one of three medications currently FDA approved for use in FMS management. Duloxetine is a mixed serotonin and norepinephrine reuptake inhibitor (SNRI) that functions by increasing central nervous system levels of serotonin and norepinephrine. This review is a primer on use of duloxetine in FMS management and includes information on pharmacology and pharmacokinetics, a review of the three duloxetine FMS treatment trials currently in publication, a discussion of the safety and tolerability of duloxetine, and patient-focused perspectives on duloxetine use in FMS management. Duloxetine has proven efficacy in managing pain and mood symptoms in adult FMS patients with and without major depressive disorder. However, due to side effects, duloxetine must be used with caution in patients with fatigue, insomnia, gastrointestinal complaints, headache, cardiovascular disease, bleeding-risk, and in those 24 years of age and younger due to risk of suicidality. Duloxetine use should be avoided in patients with liver disease or alcoholics. As with all medications, duloxetine is best used as part of an individualized regimen that includes nonpharmacologic modalities of exercise, education and behavioral therapies.
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PMID:Duloxetine for the management of fibromyalgia syndrome. 2119 98

Duloxetine is a serotonin-norepinephrine reuptake inhibitor approved by the US Food and Drug Administration for the treatment of fibromyalgia and painful diabetic neuropathy at doses of 60 mg daily. Duloxetine has been shown to significantly improve the symptoms of chronic pain associated with these disorders, as measured by the Fibromyalgia Impact Questionnaire, Brief Pain Inventory scores, the Clinical Global Impressions Scale, and other various outcome measures in several placebo-controlled, randomized, double-blind, multicenter studies. Symptom improvement generally began within the first few weeks, and continued for the duration of the study. In addition, the efficacy of duloxetine was found to be due to direct effects on pain symptoms rather than secondary to improvements in depression or anxiety. Adverse events including nausea, constipation, dry mouth, and insomnia, were mild and transient and occurred at relatively low rates. In conclusion, duloxetine, a selective inhibitor for the serotonin and norepinephrine transporters, is efficacious in the treatment of chronic pain associated with fibromyalgia or diabetic neuropathy, and has a predictable tolerability profile, with adverse events generally being mild to moderate.
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PMID:Duloxetine in the treatment of chronic pain due to fibromyalgia and diabetic neuropathy. 2138 50

It is unknown how antidepressants reverse mood-congruent memory bias, a cognitive core factor causing and maintaining depression. Using a double-blind, placebo-controlled, cross-over design, we investigated the effect of a short-term treatment (14 days) with the dual reuptake inhibitor duloxetine on neural correlates of mood-congruent and mood-incongruent memory formation and retrieval in healthy volunteers who underwent a sad mood induction procedure. Duloxetine did not affect acute mood state or memory performance, but interacted with brain processes mediating mood-congruent memory. It decreased activity related to successful memory formation for mood-congruent and -incongruent items in a set of brain regions comprising the putamen and the middle frontal gyrus, as well as the middle and the anterior cingulate cortex. Duloxetine specifically increased amygdala activity related to successful memory retrieval for mood-incongruent items. Here we show that short-term administration of duloxetine affects the neural correlates of emotional memory formation and retrieval in a set of brain regions whose processing is related to affective state and its regulation. While duloxetine suppressed the neural correlates of emotional memory formation in general, it specifically enhanced amygdala processes associated with mood-incongruent memory retrieval. This pattern of results shows how an antidepressant may reduce emotional memory formation and reverse mood-congruent processing biases at retrieval.
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PMID:Short-term duloxetine administration affects neural correlates of mood-congruent memory. 2177 79


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