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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reviews briefly the evidence to support current therapies in irritable bowel syndrome (IBS) and the novel therapeutic approaches on the threshold of clinical application. Fiber is indicated at a dose of at least 12 grams per day in patients with constipation-predominant IBS. Loperamide (and probably other opioid agonists) are of proven benefit in diarrhea-predominant IBS; loperamide may also aid continence by enhancing resting anal tone, but there is no evidence that it results in pain relief. In general, smooth muscle relaxants are best used sparingly, on an as-needed basis, because their overall efficacy is unclear. The 5-HT3 antagonist, alosetron, results in adequate relief of pain and improvements in bowel function in female nonconstipated patients with IBS. Psychotropic agents are important in relieving depression and are of proven benefit for pain and diarrhea in patients with depression associated with IBS. Further trials with selective serotonin reuptake inhibitors are awaited. Psychological treatments including hypnotherapy are less widely available but may play an important role in the relief of pain. In summary, current therapies targeted on the predominant symptoms in IBS are moderately successful. As the bowel sensorimotor and limbic system disturbances of IBS are more clearly understood, we should anticipate other pharmacologic approaches in the near future, including alpha-adrenergic agonists and 5-HT4 agonists. New therapies directed at treatment of the syndrome, rather than relief of symptoms, are needed.
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PMID:Therapeutic approach to the patient with irritable bowel syndrome. 1058 70

Studies were performed in the mouse forced swimming model, a well known experimental depression model, in order to detect the mechanism of the antidepressive effects induced by repeated serotonin reuptake inhibitor (SSRI) dosing. Five-day repeat dosing of a typical SSRI, paroxetine, increased climbing, a distinctive antidepressive behavior, 1 h after but not 1 h before treatment. The coinjection of paroxetine and serum in mice treated with four repeated doses of paroxetine distinctively increased the behavior, but the coinjection of paroxetine and serum in mice without paroxetine did not. These results indicate that repeated dosing of paroxetine produces a serum substance related to the antidepressive effects induced by serotonin neuron activities. Furthermore, the behavior induced by 5-day repeated dosing of paroxetine was decreased by 100 and 10 micrograms/kg of ketanserin (5-HT2 antagonist) and 100 micrograms/kg of LY-278584 (5-HT3 antagonist). The present findings strongly suggest that repeated dosing of paroxetine produces a serum substance stimulating the antidepressive neuronal pathway sensitively mediated by 5-HT2 and 5-HT3 receptor activity.
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PMID:Effects of repeated selective serotonin reuptake inhibitor paroxetine treatments on mouse forced swimming. 1066 4

The 5-HT3 receptor antagonists are a novel therapy for patients suffering from fibromyalgia, although the optimal duration of treatment is still unclear. The objective of this phase II study was to evaluate whether prolonging treatment with tropisetron to 4 weeks is tolerable and correlated with an improved clinical benefit. Thirty female patients with fibromyalgia received oral tropisetron (5 mg) daily for 28 days in an open-label fashion. Treatment resulted in significantly decreased pain as measured by visual analog scale (VAS), with a mean reduction of 59.7% and an absolute median change of -25.0 from baseline to day 28 (p<0.0001). A similar, significant reduction of 55.7% and absolute median change of -31.0 was observed in the painscore (p<0.0001). The response rate with patients showing a > or = 35% reduction in individual pain scores was 72.4% at day 28. The pressure tolerance of tender-points was slightly increased at the end of the treatment period. In addition, significant improvements were observed in the State-Trait-Anxiety-Inventory (STAI), scales of von Zerssen (Bf-S) and Beck Depression Index (BDI). Functional symptoms were compared with the results from a 10-day, randomized, double-blind phase III study of tropisetron in 418 fibromyalgia patients. In both studies several functional symptoms such as sleep disturbances and dizziness improved significantly (p<0.05). In the 28 days study, the number and extent of improvement in functional symptoms was increased compared with the shorter trial. Tolerability and safety of tropisetron was good, and typically for 5-HT3-receptor antagonists, gastrointestinal symptoms and headache were the most frequently reported events. In conclusion, 28 days treatment of fibromyalgia patients with 5 mg tropisetron resulted in significant pain reduction, which was most pronounced after 10 days with a further reduction up to day 28. Psychometric tests showed significant improvements in depression and anxiety state scores, while functional symptoms improved with extended tropisetron treatment.
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PMID:Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain. 1102 33

The negative symptoms of schizophrenia remain a major clinical challenge. Mirtazapine is an antidepressant with antagonist properties at 5-HT2A, 5-HT3 and alpha 2 receptors as well as indirect 5-HT1a agonist effects. Many of these pharmacological actions have clinical or preclinical evidence of efficacy in schizophrenia. This study was a 6-week randomized placebo-controlled trial of mirtzepine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The primary finding of the trial was a 42% reduction in Positive and Negative Syndrome Scale (PANSS) negative symptom scores in the mirtazapine group compared to placebo at the end of 6 weeks (mirtazapine 13.9, SD 1.56; placebo 23.9, SD 1.56; P = 0.000, F = 20.31, d.f. = 1). The PANNS total scores, Clinical Global Impression severity and improvement scales in addition showed superiority of mirtazapine over placebo. There was no difference between the groups on the Hamilton depression scale at endpoint, suggesting that the improvement in negative symptoms was not an artifact of mood improvement. These results suggest a potential role for mirtazapine in the negative symptoms of schizophrenia.
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PMID:Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. 1123 73

The novel antidepressant mirtazapine has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors. It enhances, therefore, the release of norepinephrine and 5-HT1A-mediated serotonergic transmission. This dual mode of action may conceivably be responsible for mirtazapine's rapid onset of action. Mirtazapine is extensively metabolized in the liver. The cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4 are mainly responsible for its metabolism. Using once daily dosing, steady-state concentrations are reached after 4 days in adults and 6 days in the elderly. In vitro studies suggest that mirtazapine is unlikely to cause clinically significant drug-drug interactions. Dry mouth, sedation, and increases in appetite and body weight are the most common adverse effects. In contrast to selective serotonin reuptake inhibitors (SSRIs), mirtazapine has no sexual side effects. The antidepressant efficacy of mirtazapine was established in several placebo-controlled trials. In major depression, its efficacy is comparable to that of amitriptyline, clomipramine, doxepin, fluoxetine, paroxetine, citalopram, or venlafaxine. Mirtazapine also appears to be useful in patients suffering from depression comorbid with anxiety symptoms and sleep disturbance. It seems to be safe and effective during long-term use.
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PMID:A review of the pharmacological and clinical profile of mirtazapine. 1160 47

This review summarizes the current knowledge of the biosynthesis of neurosteroids in the human brain, the enzymes mediating these reactions, their localization and the putative effects of neurosteroids. Molecular biological and biochemical studies have now firmly established the presence of the steroidogenic enzymes cytochrome P450 cholesterol side-chain cleavage (P450SCC), aromatase, 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase in human brain. The functions attributed to specific neurosteroids include modulation of gamma-aminobutyric acid A (GABAA), N-methyl-d-aspartate (NMDA), nicotinic, muscarinic, serotonin (5-HT3), kainate, glycine and sigma receptors, neuroprotection and induction of neurite outgrowth, dendritic spines and synaptogenesis. The first clinical investigations in humans produced evidence for an involvement of neuroactive steroids in conditions such as fatigue during pregnancy, premenstrual syndrome, post partum depression, catamenial epilepsy, depressive disorders and dementia disorders. Better knowledge of the biochemical pathways of neurosteroidogenesis and their actions on the brain seems to open new perspectives in the understanding of the physiology of the human brain as well as in the pharmacological treatment of its disturbances.
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PMID:Neurosteroid metabolism in the human brain. 1172 Aug 89

The efforts of clinical researchers, lay organizations and pharmaceutical companies have increased the public profile of irritable bowel syndrome and made it a respectable diagnosis. Diagnostic symptom criteria encourage a firm clinical diagnosis, which is the foundation of a logical management strategy. This begins with education. Reassurance that no structural disease threatens should be tempered with the reality that symptoms are likely to recur over many years. Patients expect diet and lifestyle advice, even if this is not specific to irritable bowel syndrome. Only a few of those with irritable bowel syndrome see doctors, and even fewer see specialists. Therefore, the treating physician should ascertain the reason for the visit, the patient's fears and the presence of any comorbid illness, such as depression, that might require treatment in its own right. No drug treatment is useful for all of the symptoms of irritable bowel syndrome, and many patients require no drug at all. If used, drugs should target the predominant symptom. Alosetron, a 5-HT3 antagonist, is effective in treating women with irritable bowel syndrome who also have diarrhoea. Tegaserod, a 5-HT4 agonist, is useful for women with irritable bowel syndrome who are constipated. Most patients with irritable bowel syndrome need psychological support. Reassurance, discussion and relaxation techniques can be provided by the family doctor. Difficult psychopathology may require referral to a mental health professional, and the gastroenterologist can settle diagnostic uncertainties. In all cases, successful treatment depends on a confident diagnosis and the strength of the doctor-patient relationship.
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PMID:The treatment of irritable bowel syndrome. 1218 40

Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin but acts as an antagonist at presynaptic alpha(2)-receptors, at postsynaptic 5-HT2 and 5-HT3 receptors, and at histaminergic H1 receptors. Furthermore, mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on salivary cortisol secretion was investigated in 12 patients (4 men, 8 women) suffering from major depression according to DSM-IV criteria. Patients were treated with mirtazapine for 3 weeks, receiving 15 mg mirtazapine on day 0, 30 mg on day 1 and 45 mg per day from day 2 up to the end of the study (day 21). Response to mirtazapine treatment was defined by a reduction of at least 50% in the Hamilton Rating Scale for Depression after 3 weeks of therapy. Salivary cortisol concentrations were measured before treatment (day -1), at the beginning of treatment (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Saliva samples were collected hourly from 08.00 until 20.00 h. The area under the curve values served as parameter for the salivary cortisol secretion. Following analysis of variance with a repeated measures design, tests with contrasts revealed a significant reduction of cortisol concentrations already after 1 day of mirtazapine treatment that was comparable in responders and nonresponders. In addition to new pharmacological approaches such as CRH1 receptor antagonists, mirtazapine therefore appears to be an effective strategy to decrease hypercortisolism and restore HPA system dysregulation in depression. However, the importance of the acute inhibitory effects of mirtazapine on cortisol secretion for its antidepressant efficacy has to be further clarified.
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PMID:Influence of mirtazapine on salivary cortisol in depressed patients. 1260 43

As described elsewhere the oral administration of 5 mg of the 5-HT3-receptor-antagonist Tropisetron in fibromyalgia exhibited less amelioration of pain in patients with a depression in comparison to patients without depression. Since an intravenous treatment seems to increase the effect of Tropisetron, the question arises whether patients with depression profit from the intravenous therapy. Methods 68 out patients with fibromyalgia according to ACR-criteria were enrolled in the study. The patients filled in a VAS pain and the Beck Depression Inventory (BDI) before and after a bolus i.v. injection of 5 mg Tropisetron for 5 days [Beck AT, Steer Ra. Beck-Depression-Inventory (BDI) In: Hautzinger M (Hrsg der dt. Ausg.). Testhandbuch. 1. Auflage Bern: Verlag Hans Huber, 1994]. In the beginning the patients had to have > or = 40 mm in the VAS pain from 0-100 mm. The patients were divided into three groups: group 1 = patients with a BDI<19 without experience with antidepressive drugs (n=26); group 2=patients with a BDI > or = 19 (n=22) and negative experience with antidepressive substances, and group 3=patients with a BDI > or = 19 and an accompanying antidepressant drug therapy and some benefit under this therapy (n=20). Results Before the therapy there was no significant difference in VAS pain in the groups, but in BDI there was a significant difference between group 1 (BDI mean value 11.5) in comparison to group 2 (BDI mean value 26.1) and group 3 (BDI mean value 24.8). After therapy all three groups had a significant amelioration of pain: group 1: p=0.000023; group 2: p=0.00073; group 3: p=0.0145. There was a significant difference between the group with BDI<19 and the group with antidepressant drug in amelioration of pain (p=0.044). A significant correlation was found in group 2 with Beck > or = 19 between amelioration of pain and BDI after therapy (p=0.008, r=0.666). In this group a pain-reactive depression and in group 3 an endogenous depression must be discussed.
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PMID:[The influence of depression on the effect of Tropisetron in the therapy of fibromyalgia]. 1262 2

The purpose of this review is to discuss pharmacological options for the treatment of patients with eating disorders. Sequentially described are pharmacotherapy studies of anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED). The quantity of drug trials performed with AN patients has been very limited. While the majority of studies have failed to show medication efficacy for the acute treatment of AN, there is data which suggests that fluoxetine hydrochloride may play a role in preventing relapse during maintenance therapy. Atypical antipsychotics, most often olanzapine, have shown promise in a number of uncontrolled studies. BN has been most extensively studied, with the majority of pharmacological trials focusing on antidepressants. Fluoxetine, at a dose of 60 mg/day, is FDA-approved for the treatment of BN. Psychotherapy, particularly cognitive behavioural therapy (CBT) is of well-established utility in BN and data suggests that the combination of an antidepressant plus CBT is superior to either treatment alone. Recently, there has been interest in the 5-HT3 antagonist, ondansetron, and the anticonvulsant, topiramate. BED investigators have focused largely on antidepressants, which may reduce symptoms of depression and augment psychotherapy. While sibutramine and topiramate have both been associated with weight loss in controlled trials, the former appears to be fairly well-tolerated and the latter appears to be responsible for the emergence of significant cognitive and peripheral nervous system side effects in some patients. Further pharmacological research with eating disorder patients is needed, particularly in the areas of AN and BED. Also, pharmacological augmentation strategies for those not responding to primary therapies should be explored.
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PMID:Towards the pharmacotherapy of eating disorders. 1452 77


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