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Subjects were 114 HIV-infected men with pain associated with peripheral neuropathy in the early 1990s, when antiretroviral drug cocktails were just beginning to be available in experimental form.
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We present a detailed review of the medications used in the USA, Canada, and the United Kingdom for the prevention of migraine and the potential ocular adverse effects associated with the use of these medications. Those drugs that are administered for the purpose of reducing the frequency or severity of migraine attacks are classified according to whether they act on the cerebral vasculature primarily at serotonin (5-HT2) receptors (e.g., methysergide, cyproheptadine, and pizotyline), beta adrenergic (primarily beta-2) receptors (e.g., propranolol and timolol), via central nervous system (CNS) adrenergic (alpha-2) receptors (e.g., clonidine), or calcium channels (e.g., flunarizine). The roles and mechanisms of action of tricyclic antidepressants (e.g., amitriptyline) and nonsteroidal anti-inflammatory drugs (NSAIDs) in the prophylactic management of migraine are also discussed, along with possible pharmacogenetic differences in the kinetics of action of some of these drugs. The general indications, contraindications, and potential ocular and systemic adverse effects of each class of drugs is reviewed and presented along with the references to original literature on these effects.
A three-year retrospective review of neuroleptic drug use at the Family Practice Center of the Medical University of South Carolina was conducted. The charts of 73 patients who had taken neuroleptic agents were reviewed for compliance with the most recent guidelines established by the National Institute of Mental Health (NIMH). Information retrieved included: age, sex, number of clinic visits, diagnosis, neuroleptic agent used, dosages, duration of therapy, concomitant psychotropics, antiparkinson agents, and extrapyramidal side effects. Neuroleptic drug use was considered inappropriate for 26% of the patients' diagnoses. Twenty percent of the dosage regimens were outside the ranges recommended by NIMH. Almost 15% of the medications used consisted of th fixed-combination products of perphenazine and amitriptyline hydrochloride, and 77% of these prescriptions were for dosages below the recommended amounts. Polypsychopharmacy was a common problem, with 36% of the patients receiving one or more psychotropic drugs with a neuroleptic agent. Nineteen patients (26%) had been prescribed an inappropriate psychotropic combination. Nine patients (12%) had received antiparkinson agents. Eight patients (11%) had documented extrapyramidal side effects. Neuroleptic drug use was found to be suboptimal. Various deficiencies were documented particularly in the use of fixed-combination products and because of the problems associated with polypsychopharmacy.
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Migraine interferes with the quality of life of patients. Prophylactic medication is an option to be considered in cases showing inefficiency of symptomatic medication or an increase in the number of attacks.
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Baseline data, collected upon admission to the rehabilitation intervention was compared to follow-up data collected by telephone interview. Data was evaluated for differences and relationships using the appropriate parametric or non-parametric tests.
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In the context of chronic physical illness, such as breast cancer, depression is associated with increased morbidity, longer periods of hospitalization, and greater overall disability. Prompt diagnosis and effective treatment is. therefore, essential. Several small studies have established the efficacy of tricyclic antidepressants (TCAs) in this setting, and the selective serotonin reuptake inhibitors (SSRIs) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile. This was a multicenter. double-blind, parallel-group study in which 179 women with breast cancer were randomized to treatment with either the SSRI paroxetine (20-40 mg/day), or the TCA, amitriptyline (75-150 mg/day). After 8-weeks treatment, depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale. Clinical global impression (CGI) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint: a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale. A steady improvement in quality of life was also observed in both groups. There were no clinically significant differences between the groups. In total, 47 (53.4%) patients in the paroxetine group and 53 (59.6%) patients in the amitriptyline group had adverse experiences, the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy. Anticholinergic effects were almost twice as frequent in the amitriptyline group (19.1%) compared with paroxetine (11.4%). This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer.
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Management of painful peripheral neuropathies remains challenging, since patients with chronic pain respond poorly to the available pharmacopeia. In recent years, the G-protein-coupled receptor neurotensin (NT) type 2 (NTS2) emerged as an attractive target for treating transitory pain states. To date, however, there is no evidence for its role in the regulation of chronic peripheral neuropathies. Here, we found that NTS2 receptors were largely localized to primary afferent fibers and superficial dorsal horns. Changes in the time course of the gene expression profile of NT, NTS1, and NTS2 were observed over a 28-d period following the sciatic nerve constriction [chronic constriction injury (CCI) model]. We next determined the effects of central delivery of selective-NTS2 agonists to CCI-treated rats on both mechanical allodynia (evoked withdrawal responses) and weight-bearing deficits (discomfort and quality-of-life proxies). The NTS2 analogs JMV431, levocabastine, and β-lactotensin were all effective in reducing ongoing tactile allodynia in CCI-treated rats. Likewise, amitriptyline, pregabalin, and morphine significantly attenuated CCI-induced mechanical hypersensitivity. NTS2 agonists were also efficient in reversing weight-bearing and postural deficits caused by nerve damage, unlike reference analgesics currently used in the clinic. Thus, NTS2 agonists may offer new treatment avenues for limiting pain associated with peripheral neuropathies and improve functional rehabilitation and well-being.
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The tricyclic antidepressant, amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine. However, its efficacy in episodic tension-type headache has not yet been clarified. We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study. Amitriptyline significantly reduced (P < 0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache. Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.
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OBJECTIVE (BACKGROUND): Amitriptyline (AT) is a standard therapy for postherpetic neuralgia (PHN). Our hypothesis was that nortriptyline (NT), a noradrenergic metabolite of AT, may be more effective.
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A sociodemographic and clinical picture is presented of 82 depressed subjects who had an unequivocal response or lack of response to treatment with amitriptyline or imipramine. Patients with less severe depressive illness were found more likely to respond to treatment, while those with psychotic features were more likely to be treatment resistant. Sociodemographic and other prior and current clinical course variables were not predictive of treatment response in depressed patients.
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Cystic fibrosis is a hereditary metabolic disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and characterized by severe intestinal and pulmonary symptoms, in particular intestinal obstruction, pancreatic insufficiency, chronic pulmonary inflammation, and microbial lung infections. Recent studies have demonstrated an accumulation of ceramide in the lungs of cystic fibrosis patients and in several mouse models. These findings showed that pulmonary ceramide concentrations play an important role in pulmonary inflammation and infection. In this study we investigated whether ceramide concentrations are also altered in the trachea and the intestine of cystic fibrosis mice and whether an accumulation of ceramide in these organs has functional consequences that are typical of cystic fibrosis. Our findings demonstrate a marked accumulation of ceramide in tracheal and intestinal epithelial cells of cystic fibrosis mice. When acid sphingomyelinase activity is inhibited by treating cystic fibrosis mice with amitriptyline or by genetic heterozygosity of acid sphingomyelinase in cystic fibrosis mice, ceramide concentrations in the trachea and the intestine are normalized. Moreover, increased rates of cell death and increased cytokine concentrations in the trachea, the intestine, or both were normalized by the inhibition of acid sphingomyelinase activity and the concomitant normalization of ceramide concentrations. These findings suggest that ceramide plays a crucial role in inflammation and increased rates of cell death in several organs of cystic fibrosis mice.