Cns Drugs
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Increasing numbers of reports concerning diabetes, ketoacidosis, hyperglycaemia and lipid dysregulation in patients treated with second-generation (or atypical) antipsychotics have raised concerns about a possible association between these metabolic effects and treatment with these medications. This comprehensive literature review considers the evidence for and against an association between glucose or lipid dysregulation and eight separate second-generation antipsychotics currently available in the US and/or Europe, specifically clozapine, olanzapine, risperidone, quetiapine, zotepine, amisulpride, ziprasidone and aripiprazole. This review also includes an assessment of the potential contributory role of treatment-induced weight gain in conferring risk for hyperglycaemia and dyslipidaemia during treatment with different antipsychotic medications. ⋯ However, case reports tentatively suggest that substantial weight gain or obesity may not be a factor in up to one-quarter of cases of new-onset diabetes that occur during treatment. Pending further testing from preclinical and clinical studies, limited controlled studies support the hypothesis that clozapine and olanzapine may have a direct effect on glucose regulation independent of adiposity. The results of studies in this area are relevant to primary and secondary prevention efforts that aim to address the multiple factors that contribute to increased prevalence of type 2 diabetes mellitus and cardiovascular disease in populations that are often treated with second-generation antipsychotic medications.
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Review Comparative Study
Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same?
Selective serotonin 5-HT(3) receptor antagonists have proven safe and effective for the management of postoperative nausea and vomiting. Dolasetron, granisetron, ondansetron and tropisetron selectively and competitively bind to 5-HT(3) receptors, blocking serotonin binding at vagal afferents in the gut and in the regions of the CNS involved in emesis, including the chemoreceptor trigger zone and the nucleus tractus solitarii. ⋯ Hence, although these agents are considered equally effective in the overall population, their pharmacokinetic and pharmacodynamic differences may explain the variability in individual responses to these drugs. This review discusses the pharmacological profiles of dolasetron, granisetron, ondansetron and tropisetron, and the clinical implications of differences in their profiles.
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Medication overuse headache (MOH) is a common medical condition that is associated with considerable long-term morbidity and disability. Patients experiencing MOH have primary headache disorders (migraine, tension-type headache [TTH] or the combination of migraine and TTH) that change to a pattern of daily or near-daily headaches over a period of years or decades following the overuse of symptomatic headache medications. Overused drugs include analgesics, ergot alkaloids, serotonin 5-HT(1B/1D) receptor agonists ('triptans') and medications containing barbiturates, codeine, caffeine, tranquillisers and mixed analgesics. ⋯ Most patients respond to this therapy, although the prognosis is not always good and >or=50% may lapse over an initial 5-year follow-up period. The best practical strategy at present is to prevent the overuse of drugs in the first place by patient education and formal management approaches conducted in primary care to treat the primary headache before it changes to MOH. The quality of the clinical evidence on MOH is suboptimal and further biological and clinical research is urgently required to help facilitate the management of these patients more effectively in the future.
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Review
Intravenous thrombolysis in acute ischaemic stroke: optimising its use in routine clinical practice.
Stroke is a common and important medical problem. Intravenous thrombolysis with alteplase (recombinant tissue plasminogen activator; rtPA) is the only available direct treatment that reduces neurological injury following ischaemic stroke. Strong efficacy data from randomised, controlled trials support the use of intravenous thrombolysis to improve outcomes for patients with acute ischaemic stroke. ⋯ Protocol violations must be avoided because they are associated with adverse events including higher mortality and increased haemorrhagic complications. Although thrombolytic therapy with alteplase is currently being used in only <10% of patients with acute ischaemic stroke, recent studies demonstrate that quality management efforts can improve both the absolute rate of use as well as the proficiency with which alteplase is administered. Given the complexities inherent in prescribing thrombolysis for patients with acute ischaemic stroke, alteplase should be used by clinicians who are experienced in the diagnosis and management of stroke, working in medical centres that have systems in place to ensure that alteplase is given without protocol violations.
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DSM-IV has recommended use of the Social and Occupational Functioning Scale (SOFAS) as a clinician-rated global assessment scale for measuring social functioning; this scale is analogous to the Clinical Global Impression (CGI) scale traditionally used as a secondary outcome measure in patients with depressive symptoms. However, we believe that health-related quality of life is the most appropriate indicator of social functioning when considering this dimension as an endpoint in clinical trials of antidepressants. As health-related quality of life is a purely subjective measure, patient-rated questionnaires have been found to be most important in this context. ⋯ In medium- and long-term trials, SF-36 subscales should be used as a supplement to symptom-orientated scales. In trials of shorter (6-8 weeks) duration, use of other scales such as the SAS-SR, the Q-LES-Q or the Sheehan Disability Scale should be considered. These scales should be considered as supplementary to each other rather than alternatives; it may be necessary to use more than one of these scales in a trial.