UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. Limited clinical trials suggest that hypericum and standard antidepressants have similar beneficial effects, but current evidence regarding the antidepression effects of SJW extracts is inconsistent. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs. This review highlights and updates the knowledge regarding drug interactions with SJW by a systematic review of all the available evidence, including worldwide published literature and spontaneous case reports. A number of clinically significant interactions of SJW have been identified with conventional drugs. These interactions often result in a decrease in the concentration or effect of the combined drug, most probably due to the induction of cytochrome P450s (CYPs) and the key drug transporter P-glycoprotein (P-gp) by the major active constituents in SJW. SJW is a potent inducer of human CYP3A4 and P-gp in vitro and in vivo. In addition, pharmacodynamic interactions of SJW with some drugs (e.g. selective serotonin re-uptake inhibitors) have been identified, which are associated with an increased risk of adverse reactions. Since potential interactions of SJW with conventional drugs is a major safety concern, it is important to minimize and avoid these interactions by taking appropriate approaches. These include systematic research to identify SJW-drug interaction; close therapeutic drug monitoring when SJW is combined with conventional drugs with a narrow therapeutic window; proper dose and regimen adjustment; patient education and communication between the patient and physician; design of new preparations of SJW without inducing ability of CYP3A4 and P-gp while retaining its bioactivity; and appropriate regulation in herbal safety and efficacy. Further clinical and mechanistic studies are warranted to explore the interaction of SJW with other important drugs and clinical significance.
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PMID:An update on clinical drug interactions with the herbal antidepressant St. John's wort. 1853 76

Estrogen and androgen are synthesized from cholesterol locally in hippocampal neurons of adult animals. These neurosteroids are synthesized by cytochrome P450s and hydroxysteroid dehydrogenases (HSDs) and 5alpha-reductase. The expression levels of enzymes are as low as 1/200-1/50,000 of those in endocrine organs, however these numbers are high enough for local synthesis. Localization of P450(17alpha), P450arom, 17beta-HSD and 5alpha-reductase is observed in principal glutamatergic neurons in CA1, CA3 and the dendate gyrus. Several nanomolar levels of estrogen and androgen are observed in the hippocampus. Estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly in the hippocampus. Rapid action of 17beta-estradiol via membrane receptors is demonstrated for spinogenesis and long-term depression (LTD). The enhancement of LTD by 1-10nM estradiol occurs within 1 h. The density of spine is increased in CA1 pyramidal neurons within 2h after application of estradiol. The density of spine-like structure is, however, decreased by estradiol in CA3 pyramidal neurons. ERalpha, but not ERbeta, induces the same enhancement/suppression effects on both spinogenesis and LTD.
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PMID:Estrogen synthesis in the brain--role in synaptic plasticity and memory. 1854 62

St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs that have distinctive chemical structure, mechanism of action and metabolic pathways. This review highlights and updates the knowledge on clinical interactions of prescribed drugs with SJW and the implication in drug development. A number of clinically significant interactions of SJW have been identified with conventional drugs, including anticancer agents (imatinib and irinotecan), anti-HIV agents (e.g. indinavir, lamivudine and nevirapine), anti-inflammatory agents (e.g. ibuprofen and fexofenadine), antimicrobial agents (e.g. erythromycin and voriconazole), cardiovascular drugs (e.g. digoxin, ivabradine, warfarin, verapamil, nifedipine and talinolol), central nervous system agents (e.g. amitriptyline, buspirone, phenytoin, methadone, midazolam, alprazolam, and sertraline), hypoglycaemic agents (e.g. tolbutamide and gliclazide), immuno-modulating agents (e.g. cyclosporine and tacrolimus), oral contraceptives, proton pump inhibitor (e.g. omeprazole), respiratory system agent (e.g. theophylline), statins (e.g. atorvastatin and pravastatin). Both pharmacokinetic and pharmacodynamic components may play a role in the interactions of drugs with SJW. For pharmacokinetic changes of drugs by SJW, induction of cytochrome P450s (e.g. CYP2C9 and 3A4) and P-glycoprotein (P-gp) are considered the major mechanism. Thus, it is not a surprise that many drugs that interact with SJW are substrates of CYP3A4, CYP2C9 and P-gp. A comprehensive understanding of clinical drugs that interact with SJW has important implications in drug development. New drugs may be designed to minimize interactions with SJW; and new SJW formulations may be designed to avoid drug interactions. Further clinical and mechanistic studies are warranted to explore the interaction of SJW with other important drugs and the potential clinical impact.
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PMID:Clinical drugs that interact with St. John's wort and implication in drug development. 1867 95

Recently, the number of workers who suffer from job stress was increasing in Japan because of a prolonged recession, increasing number of elderly workers, and structural reorganization of companies. On the other hand, polymorphism associated with depression or alcoholism was detected. Relationship between job stress and these polymorphisms were investigated. Brief job stress questionnaire was assessed for 243 employees who worked at a manufacturing company and a local hospital in Japan (mean age 40.8 years). Alcohol consumption and smoking habit were assessed as lifestyle factors. DNA samples were prepared to detect polymorphisms of 5HTT, aldehyde dehydrogenase 2 (ALDH2), D2 dopamine receptor (DRD2), and cytochrome p450 2A6 (CYP2A6) genes. The level of depressed mood by job stress was significantly higher among carriers of two short alleles of the 5HTT regulatory region compared with carriers of one or two long alleles (Mann-Whitney U, p<0.05). In a logistic regression analysis, the s/s allele of the 5HTT had a tendency to be a risk of depressed mood. When subjects had high supervisor's support, depressed mood was significantly lower irrespective of 5HTT polymorphism. Job stress may elicit biological responses that contribute to depressed mood in relation to 5HTT polymorphism.
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PMID:5HTT polymorphisms are associated with job stress in Japanese workers. 1925 54

Milnacipran is a dual-action antidepressant which inhibits both serotonin and norepinephrine reuptake. To our knowledge, it has limited affinity for most monoamine neurotransmitter receptors. With limited pharmacokinetic interaction with the cytochrome 450 system, milnacipran may have a low risk in drug interaction. The present study compares milnacipran with paroxetine, a selective serotonin reuptake inhibitor (SSRI) and which has been used clinically for years to evaluate the efficacy, patient tolerance, and side effects in the treatment of major depression. The study took place in two medical centers located in Northern and Southern Taiwan. Six-three participant who met the Diagnostic and Statistical Manual of Mental Disorder 4th edition (DSM-IV) criteria for a major depressive disorder and a total Hamilton Depression Rating Scale (HAM-D) score > or = 16 on the 17 item scale, were recruited. Participants first received either 100 mg/day of milnacipran (33 participants) or 20 mg/day of paroxetine (30 participants), and were then assessed with HAM-D and clinical global impression scale (CGI) for severity of the illness and global improvement, at the beginning and the end of the first, second, fourth, and eighth weeks of the drug treatment. Thirty-eight patients with major depressive disorder completed the study. No statistically significant differences were observed between the two groups in the reduction of HAM-D and CGI scores. However, side effects such as headache and tremor in the first week, psychomotor retardation and difficulty in concentration in the fourth week, and psychomotor retardation in the eighth week of treatment were significantly lower in the milnacipran group, as compared to that of the paroxetine group. We concluded that milnacipran and paroxetine had similar clinical effectiveness during the eight-week treatment of major depressive disorder. Further investigation is needed to examine the clinical suitability of this drug for patients with liver impairments and for elderly patients suffering from major depression.
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PMID:Lower side effects of milnacipran than paroxetine in the treatment of major depression disorder among Han Chinese in Taiwan. 1928 Aug 83

Cytochrome P450 genes are involved in the metabolism of antidepressants and could influence treatment response. The aim of this study was to investigate the role of allelic variations of the cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes in antidepressant treatment response and remission rates. Two hundred and seventy-eight patients affected by major depression, responders (N = 81) and nonresponders (N=197) to at least one adequate antidepressant treatment, were recruited with a multicentre design for resistant depression and genotyped for all relevant variations. None of the considered metabolic profiles (e.g. poor, intermediate, extensive and ultrarapid metabolizers) was found to be associated with either response or remission rates. In conclusion, the investigated cytochrome genes do not seem to play a major role in antidepressant response in the present sample of depressive patients. Nevertheless, methodological and sample size limitations of this study do not allow definitive conclusions.
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PMID:Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes are not associated with response and remission in a sample of depressive patients. 1959 58

Milnacipran is a serotonin and norepinephrine reuptake inhibitor (SNRI) with negligible effects on any presynaptic or postsynaptic receptors. Milnacipran has unique pharmacokinetic and pharmacodynamic characteristics that distinguish it from the other marketed serotonin and norepinephrine reuptake inhibitors, venlafaxine, desvenlafaxine, and duloxetine such as equipotent serotonin and norepinephrine reuptake inhibition and a linear dose-concentration trend at therapeutic doses. The half-life of milnacipran is approximately 8 hours. In addition, milnacipran does not inhibit the cytochrome P 450 system, indicating minimal propensity for drug-drug interactions. The antidepressant efficacy of milnacipran has been clearly established in a number of randomized, double-blind, placebo-controlled clinical trials, and it has been widely used for treating major depressive disorder. Moreover, evidence suggests that milnacipran is effective and tolerable in the treatment of fibromyalgia and may have usefulness for fatigue and anxiety symptoms. The current paper reviews researches conducted to date that is relevant to the efficacy, tolerability, and mechanism of action of milnacipran in the treatment of depression, fibromyalgia, and other psychiatric syndromes. Future directions of research are also identified.
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PMID:Milnacipran: beyond a role of antidepressant. 1962 Aug 45

1. By means of the Warburg-Barcroft microrespirometer apparatus and the Warburg direct method, the relative effect of caffeine upon the O(2) consumption of the fertilized egg of Arbacia punctulata was shown for the following concentrations in sea water: 0.002 per cent (M/10,000), 0.004 per cent (M/5,000), 0.02 per cent (M/1,000), 0.1 per cent (M/200), 0.2 per cent (M/100), 0.5 per cent (M/40), and 2 per cent (M/10). 2. In comparison with the normal eggs (uninhibited, non-caffeine-treated controls), caffeine in concentrations including and greater than 0.1 per cent (M/200) depressed the average uptake from approximately 25 to 61 per cent over the 3 hour period. In a number of instances, as typified by Experiment 10, the effective inhibitory concentration ranged from 0.02 per cent (M/1,000) upward and the degree of depression of the O(2) consumption ranged from 10.6 per cent to 60.6 per cent. 3. All caffeine concentrations including and above 0.02 per cent (M/1,000) in the series used, resulted in decreasing the normal rate of cleavage division in the fertilized Arbacia eggs. 4. The higher concentrations (0.5 and 2 per cent) produced a complete blockage of the cleavage process. 5. Complete cleavage inhibition was noted only when the O(2) uptake had been depressed to 50 per cent or more of the normal controls. 6. O(2) consumption-time relationship data indicate an average depression, in O(2) consumption over a 3 hour period, ranging from 25 per cent with a caffeine concentration of 0.1 per cent to a 61 per cent inhibition with a concentration of 2 per cent. 7. Concentrations of less than 0.1 per cent (certainly of less than 0.02 per cent) give variable results and indicate no significant effect. 8. It is inferred from the respiration data presented that it is probable that the inhibition of the O(2) consumption in fertilized Arbacia eggs is due to the influence of caffeine upon the main (activity or primary) pathway. It will be observed that there are certain similarities of the caffeine data to the degree of inhibition accomplished by sodium cyanide. Moreover, it has been demonstrated that the cyanide probably acts on the cytochrome oxidase step in the cytochrome oxidase-cytochrome chain of reactions constituting the O(2) uptake phase of respiratory metabolism. It is not improbable, therefore, that caffeine also may act upon the cytochrome oxidase enzyme. 9. From the viewpoint of environmental conditions influencing reproductive phenomena, it is of interest that caffeine can affect the normal metabolism of the zygote.
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PMID:THE EFFECTS OF CAFFEINE ON OXYGEN CONSUMPTION AND CELL DIVISION IN THE FERTILIZED EGG OF THE SEA URCHIN, ARBACIA PUNCTULATA. 1987 45

During winter, low temperatures induce a direct metabolic depression in gilthead sea bream, without any significant compensatory effect below 13 degrees C. The present study therefore focused on how to improve response to cold in these fish, looking specifically at the two factors of diet (high energy, HiE, and low energy, LoE) and activity (normal, -SW, and sustained activity, +SW) prior to exposure to cold. Following a preparatory period of 75 days water was adjusted to 10 degrees C and kept for 40 days. Enzymatic activities and store deposition revealed that the HiE-SW group had acquired an energy surplus whilst the LoE+SW group exhibited an energy deficit. Liver enzyme activities evidenced diet dependence: LoE groups showed greater glucose-6-phosphate dehydrogenase activity and HiE groups showed greater lipoprotein lipase and hepatic lipase activities. Moreover, the HiE-SW group's lower citrate synthase/cytochrome-c-oxidase ratio reflected the energy surplus available. Perivisceral fat mobilisation caused by cold stress affected liver integrity, resulting in a pre-steatotic condition for the HE-SW group. The differences in liver enzyme activities produced by pre-cold conditions disappeared at low temperatures and enzymatic activities did not compensate. Therefore any improvement that would enable gilthead sea bream to face up to winter must be achieved prior to the appearance of low temperatures.
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PMID:Energy reserves and metabolic status affect the acclimation of gilthead sea bream (Sparus aurata) to cold. 1993 33

The objective of this paper is to provide an overview of the recent developments in muscle physiology and biochemistry in general, and with respect to chronic obstructive pulmonary disease (COPD) specifically. As a way of illustration, we have presented data on the remodeling that occurs in vastus lateralis in two patients with COPD (COPD #1, forced expiratory volume in one second/forced vital capacity [FEV(1)/FVC] = 63%; COPD #2, FEV(1)/FVC = 41%) exhibiting differences in muscle wasting as compared to healthy controls (CON; FEV(1)/FVC = 111 +/- 2.2%, n = 4). Type I fibers percentages were lower in both COPD #1 (16.7) and COPD #2 (24.9) compared to CON (57.3 +/- 5.2). Cross sectional area of the type I fibers of the patients ranged between 65%-68% of CON and for the type II subtypes (IIA, IIAX, IIX) between 74% and 89% (COPD #1) and 17%-32% (COPD #2). A lower number of capillary contacts were observed for all fiber types in COPD #1 but not COPD #2. Lower concentrations of adenosine triphosphate (ATP) (24%-26%) and phosphocreatine (18%-20%), but not lactate occurred in COPD. In contrast to COPD #1, who displayed normal glucose transporter content, GLUT1 and GLUT4 were only 71% and 54%, respectively of CON in COPD #2. Lower monocarboxylate contents were found for MCT1 in both COPD #1 (63%) and COPD #2 (41%) and for MCT4 (78%) in COPD #1. Maximal oxidative enzyme activities (V(max)) for COPD #2 ranged between 37% (succinic dehydrogenase) and 70% (cytochrome C oxidase) of CON. For the cytosolic enzymes, V(max) ranged between 89% (hexokinase) to 31% (pyruvate kinase) of CON. Depressions were also observed in V(max) of the Na(+)-K(+)-ATPase for COPD #1 (66% of CON) but not COPD #2 (92% of CON) while V(max) of the Ca(2+)-ATPase was near normal in COPD #1 (84% CON). It is concluded that disturbances can occur in muscle to a wide range of excitation, contraction and metabolic processes in COPD.
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PMID:Cellular assessment of muscle in COPD: case studies of two males. 2036 Sep 8

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