Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0015672 (fatigue)
51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duloxetine (Cymbalta(R)) is a potent serotonin and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) in the CNS. It is indicated for the treatment of generalized anxiety disorder (GAD) as well as other indications. In patients with GAD of at least moderate severity, oral duloxetine 60-120 mg once daily was effective with regard to improvement from baseline in assessments of anxiety and functional impairment, and numerous other clinical endpoints. Longer-term duloxetine 60-120 mg once daily also demonstrated efficacy in preventing or delaying relapse in responders among patients with GAD. In addition, duloxetine was generally well tolerated, with most adverse events being of mild to moderate severity in patients with GAD in short- and longer-term trials. Additional comparative and pharmacoeconomic studies are required to position duloxetine among other selective serotonin reuptake inhibitors and SNRIs. However, available clinical data, and current treatment guidelines, indicate that duloxetine is an effective first-line treatment option for the management of GAD. Duloxetine is a potent and selective inhibitor of serotonin and noradrenaline transporters, and a weak inhibitor of dopamine transporters. It has a low affinity for neuronal receptors, such as alpha(1)- and alpha(2)-adrenergic, dopamine D(2), histamine H(1), muscarinic, opioid and serotonin receptors, as well as ion channel binding sites and other neurotransmitter transporters, such as choline and GABA transporters. It does not inhibit monoamine oxidase types A or B. The pharmacokinetics of duloxetine in healthy volunteers were dose proportional over the range of 40-120 mg once daily. Steady state was typically reached by day 3 of administration. Duloxetine may be administered without regard to food or time of day. Duloxetine is highly protein bound and is widely distributed throughout tissues. It is rapidly and extensively metabolized in the liver by cytochrome P450 (CYP) 1A2 and 2D6, and its numerous metabolites, which are inactive, are mainly excreted in the urine. The mean elimination half-life of duloxetine is approximately 12 hours. Duloxetine is a substrate for CYP1A2 and CYP2D6 and a moderate inhibitor of CYP2D6. Concomitant use of duloxetine and potent CYP1A2 inhibitors should be avoided and duloxetine should be used with caution in patients receiving drugs that are extensively metabolized by CYP2D6, particularly those with a narrow therapeutic index. Duloxetine was effective in the short-term treatment of patients with primary GAD of at least moderate severity. In four randomized, double-blind, placebo-controlled, multicentre, phase III trials, duloxetine 60-120 mg once daily for 9 or 10 weeks was significantly more effective than placebo with regard to the primary endpoint of mean change in Hamilton Anxiety Rating Scale (HAM-A) total score from baseline to study endpoint. In addition, all other endpoints were generally improved from baseline to a greater extent with duloxetine 60-120 mg once daily than with placebo. Duloxetine also improved patient role functioning (assessed using Sheehan Disability Scale global impairment functioning scores), health-related quality of life and patient well-being compared with placebo. Duloxetine was effective in patients with GAD who were aged >/=65 years. Pooled results of data from the two short-term efficacy trials that also included an active comparator arm showed that the mean change in HAM-A scores with duloxetine relative to placebo were of the same magnitude as those with venlafaxine extended release versus placebo. Duloxetine 60-120 mg once daily was also more effective than placebo in preventing or delaying relapse in responders to duloxetine in a longer-term study. In this study, patients with GAD received duloxetine during a 26-week, open-label, acute treatment phase and responders were then randomized to continue on duloxetine or receive placebo during a 26-week, double-blind, continuation phase. Time to relapse was significantly longer in duloxetine recipients than in placebo recipients. In addition, significantly fewer duloxetine recipients than placebo recipients relapsed during the double-blind phase of the trial and more duloxetine recipients achieved remission. Short- (9-10 weeks) and longer-term (52 weeks) treatment with duloxetine 60-120 mg once daily was generally well tolerated in patients with GAD, with the majority of adverse events being of mild to moderate severity. Nausea, dry mouth, headache, constipation, dizziness and fatigue were among the most common treatment-emergent adverse events. The adverse event profile of duloxetine did not differ with dose or treatment duration. Significantly more patients receiving short-term duloxetine than placebo discontinued treatment because of an adverse event, with nausea being the only event that resulted in significantly more treatment discontinuations in duloxetine recipients than in placebo recipients. Serious adverse events were uncommon with both short- and longer-term duloxetine treatment. Two episodes of attempted suicide and one episode of completed suicide occurred in duloxetine recipients during the 24-week open-label phase of a longer-term trial. No deaths or suicides were reported in any of the short-term trials. Discontinuation-emergent adverse events, most commonly nausea and dizziness, occurred in up to one-third of duloxetine recipients in the short-term trials.
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PMID:Duloxetine: a review of its use in the treatment of generalized anxiety disorder. 1948 Apr 70

Psychotrauma occurs as a result to a traumatic event, which may involve witnessing someone's actual death or personally experiencing serious physical injury, assault, rape and sexual abuse, being held as a hostage, or a threat to physical or psychological integrity. Post-traumatic stress disorder (PTSD) is an anxiety disorder and was defined in the past as railway spine, traumatic war neurosis, stress syndrome, shell shock, battle fatigue, combat fatigue, or post-traumatic stress syndrome (PTSS). If untreated, post-traumatic stress disorder can impair relationships of those affected and strain their families and society. Deployed soldiers are especially at a high risk to be affected by PTSD but often receive inadequate treatment. Reviews to date have focused only on a single type of treatment or groups of soldiers from only one country. The aim of the current review was to evaluate characteristics of therapeutic methods used internationally to treat male soldiers' PTSD after peacekeeping operations in South Eastern Europe and the Gulf wars.This systematic literature review returned results pertaining to the symptoms, diagnosis, timing and effectiveness of treatment. Sample groups and controls were relatively small and, therefore, the results lack generalizability. Further research is needed to understand the influence and unique psychological requirements of each specific military operation on the internationally deployed soldiers.
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PMID:Psychotrauma and effective treatment of post-traumatic stress disorder in soldiers and peacekeepers. 1964 16

The efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) once-daily monotherapy in generalized anxiety disorder (GAD) was assessed. This multicentre, double-blind, randomized, placebo- and active-controlled, phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk (8-wk active treatment, 2-wk post-treatment drug-discontinuation) study period; 873 patients were randomized to 50 mg or 150 mg quetiapine XR, 20 mg paroxetine, or placebo. Primary endpoint was change from randomization at week 8 in Hamilton Rating Scale for Anxiety (HAMA) total score. At week 8, all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR. Significant separation from placebo (-2.90) in HAMA total score was observed at day 4 for 50 mg quetiapine XR (-4.43, p<0.001) and 150 mg quetiapine XR (-3.86, p<0.05), but not for paroxetine (-2.69). Remission (HAMA total score 7) rates at week 8 were significantly higher for 150 mg quetiapine XR (42.6%, p<0.01) and paroxetine (38.8%, p<0.05) vs. placebo (27.2%). The most common adverse events (AEs) were dry mouth, somnolence, fatigue, dizziness, and headache, for quetiapine XR, and nausea, headache, dizziness for paroxetine. A lower proportion of patients reported sexual dysfunction with quetiapine XR [0.9% (50 mg), 1.8% (150 mg)] than with placebo (2.3%) or paroxetine (7.4%). The incidence of AEs potentially related to extrapyramidal symptoms was: quetiapine XR: 50 mg, 6.8%, 150 mg, 5.0%; placebo, 1.8%; and paroxetine, 8.4%. Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD, with symptom improvement seen as early as day 4.
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PMID:Extended-release quetiapine fumarate (quetiapine XR): a once-daily monotherapy effective in generalized anxiety disorder. Data from a randomized, double-blind, placebo- and active-controlled study. 1969 7

Patients with neurologic disorders commonly experience sleep dysfunction and psychiatric disorders. The most common sleep dysfunction is insomnia, which is a primary symptom in 30% to 90% of psychiatric disorders. Insomnia and fatigue are prominent symptoms of anxiety disorders and major depression that may occur in patients who are treated but have residual sleep dysfunction. Anxiety and depressive disorders account for 40% to 50% of all cases of chronic insomnia. It is also recognized that primary insomnia and other primary sleep disorders produce symptoms that are similar to those reported by patients with psychiatric disorders. A clinician must judge whether sleep deprivation causes mood disturbance or whether depressive or anxiety disorder represents the primary reason for sleep dysfunction. When insomnia is comorbid with mild to moderate depression, therapy should begin with bedtime dosing of sedating antidepressants such as mirtazapine, nefazodone, or tricyclic antidepressants, which are preferred because of their sedative effects. Often side effects limit their usefulness. Intervention for chronic insomnia is similar in nonpsychiatric and psychiatric patients. Behavioral therapies, particularly multicomponent cognitive-behavioral therapy, and lifestyle changes show significant long-term efficacy as treatments for chronic insomnia. The most studied pharmacologic agents to treat insomnia are sedative hypnotic agents, particularly those that are active through the benzodiazepine receptor-GABA (gamma-aminobutyric acid) complex, such as benzodiazepines, eszopiclone, zaleplon, and zolpidem. Melatonin and the melatonin-receptor agonist ramelteon have not had adequate study in psychiatric patients to define their use, but small studies suggest benefit. Prescription of adjunctive trazodone (50-150 mg) is a common clinical practice to treat comorbid insomnia during antidepressant therapy, but published data are surprisingly limited, considering its frequent use. Although there has been insufficient research on the use of atypical antipsychotic agents in severe insomnia, psychiatrists use quetiapine, olanzapine, or others to lessen agitation that disrupts sleep. When insomnia or hypersomnia continue even as mood, anxiety, or thought disorders improve with standard therapy, the physician should consider the potential presence of underlying sleep disorders.
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PMID:Treatment of sleep dysfunction and psychiatric disorders. 1974 1

The presentation of fibromyalgia is heterogeneous, and the treatment approach should be individualized for each patient, depending on the severity of the patient's pain, the presence of other symptoms or comorbidities, and the degree of functional impairment. The management of fibromyalgia includes the identification and treatment of all pain sources that may be present in addition to fibromyalgia, such as peripheral pain generators (e.g., comorbid osteoarthritis or neuropathic pain) or visceral pain (e.g., comorbid irritable bowel syndrome). It is also important to address other symptoms or disorders that commonly occur in patients with fibromyalgia, such as fatigue, sleep disturbances, cognitive impairment, stiffness, and mood or anxiety disorders. Finally, the treatment should strive to improve the patient's function and global health status. In most cases, the management of fibromyalgia involves both pharmacologic and nonpharmacologic treatments. This report provides an in-depth review of randomized, controlled trials for pharmacologic and nonpharmacologic approaches to fibromyalgia therapy.
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PMID:Strategies for managing fibromyalgia. 1996 95

According to the analysis in pediatrics, 5.8% of children aged equal or more than 3 years attended pediatric outpatient clinics had psychosomatic problems. The logistic regression analysis demonstrated that children with psychosomatic problems had complained more chronic fatigue (odds ratio: 2.55), headache (2.42) and recurrent abdominal pain(2.03) in comparison with controls. The other study showed many children with school phobia had trouble with class mates and complained somatoform disorders. Working with somatizing patients and their parents can be frustrating the pediatrician, and comorbid psychiatric disorders are common in these patients. To get good carryover, the psychiatric consult is needed if they have suffered from major depressive disorder, and other anxiety disorders.
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PMID:[Care continuity for children with psychosomatic disorders]. 2007 98

Generalized anxiety disorder is common among patients in primary care. Affected patients experience excessive chronic anxiety and worry about events and activities, such as their health, family, work, and finances. The anxiety and worry are difficult to control and often lead to physiologic symptoms, including fatigue, muscle tension, restlessness, and other somatic complaints. Other psychiatric problems (e.g., depression) and nonpsychiatric factors (e.g., endocrine disorders, medication adverse effects, withdrawal) must be considered in patients with possible generalized anxiety disorder. Cognitive behavior therapy and the first-line pharmacologic agents, selective serotonin reuptake inhibitors, are effective treatments. However, evidence suggests that the effects of cognitive behavior therapy may be more durable. Although complementary and alternative medicine therapies have been used, their effectiveness has not been proven in generalized anxiety disorder. Selection of the most appropriate treatment should be based on patient preference, treatment success history, and other factors that could affect adherence and subsequent effectiveness.
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PMID:Generalized anxiety disorder: practical assessment and management. 2017 60

Acupuncture has been reported to affect the autonomic system. Currently, there are no systematic reviews examining the effect of acupuncture on HRV available in the literature. Therefore, the aim of this systematic review was to summarize and critically assess the effects of acupuncture on heart rate variability. We searched the literature using 14 databases for articles published from the earliest available publications until October 2009 without language restrictions. We included randomized clinical trials (RCTs) comparing acupuncture and sham acupuncture. The risk of bias in each study was assessed using the Cochrane criteria. Twelve RCTs met all of the inclusion criteria. One RCT evaluated the effects of acupuncture in patients with minor depression or anxiety disorders and another RCT examined the effect of acupuncture on migraine patients. Another four RCTs tested the effects of acupuncture in healthy subjects who were exposed to several conditions, including mental stress, fatigue from driving, and caffeine intake. The remaining six RCTs assessed the effects of acupuncture on healthy subjects in a normal state without any stressors. Five RCTs found significant differences in HRV between patients treated with acupuncture versus those treated with sham acupuncture (controls). However, the majority of the other RCTs showed inconsistent results or did not identify significant differences in HRV spectral parameters among individuals treated with acupuncture as compared to those treated with sham acupuncture. In conclusion, sham-controlled RCTs showed variable results and no clear evidence that acupuncture has any specific effects on HRV. Therefore, more rigorous research appears to be warranted.
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PMID:Acupuncture and heart rate variability: a systematic review. 2030 8

Chronic fatigue syndrome (CFS), a complex illness characterized by fatigue, impaired concentration, and musculoskeletal pain, is often misdiagnosed as a psychiatric illness due to the overlap of its symptoms with mood and anxiety disorders. Using proton magnetic resonance spectroscopic imaging ((1)H MRSI), we previously measured levels of the major brain metabolites in CFS, in generalized anxiety disorder (GAD), and in healthy control subjects, and found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in CFS compared to the other two groups. In the present study, we sought to assess the specificity of this observation for CFS by comparing ventricular lactate levels in a new cohort of 17 CFS subjects with those in 19 healthy volunteers and in 21 subjects with major depressive disorder (MDD), which, like GAD, is a neuropsychiatric disorder that has significant symptom overlap with CFS. Ventricular CSF lactate was significantly elevated in CFS compared to healthy volunteers, replicating the major result of our previous study. Ventricular lactate measures in MDD did not differ from those in either CFS or healthy volunteers. We found a significant correlation between ventricular CSF lactate and severity of mental fatigue that was specific to the CFS group. In an exploratory analysis, we did not find evidence for altered levels of the amino acid neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate + glutamine ('Glx'), in CFS compared to MDD or healthy controls. Future (1)H MRS studies with larger sample sizes and well-characterized populations will be necessary to further clarify the sensitivity and specificity of neurometabolic abnormalities in CFS and MDD.
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PMID:Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder. 2066 76

Patients with severe and disabling pain and bodily distress which cannot be explained by underlying organic pathology are common in all levels of health care and are typically difficult to treat for physicians as well as for mental health specialists. Beside pain in different locations, not fully explained by specific somatic pathology, specific functional complaints such as dizziness, fatigue or vegetative disorders are common. A great proportion of patients with somatoform pain complain of comorbid depressive or anxiety disorder. Psychodynamic-interpersonal psychotherapy particularly emphasises interpersonal processes as well as disturbance of body awareness and self regulation already in childhood. Cognitive-behavioral models focus on the phenomenon of somatosensory amplification. The patients do have a strong believe in an underlying somatic illness, therefore seeking for further diagnostic and somatic therapy. This frequently leads to multiple but ineffective therapeutic attempts in the field of somatic medicine resulting in frustration of the patients and a difficult doctor-patient-relationship. General therapeutic recommendations include an active therapeutic approach with paying tribute for the patients' suffering and giving support to cope with the pain. A specific psychodynamic approach furthermore focuses on improvement of affect differentiation and the interaction of somatoform pain and interpersonal relationships.
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PMID:[Somatoform pain disorder - overview]. 2085 92


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