Treatment studies, evidence-based

The current evidence base for the injection of epinephrine in the initial acute treatment of anaphylaxis includes clinical experience during nearly a century of use, observational studies, epidemiological studies, fatality studies, and randomized controlled trials in people at risk for anaphylaxis although not actually experiencing it at the time of the study. Moreover, the pharmacology of epinephrine has been... 

The evidence base for clinical decisions based on cost-effectiveness for the affective disorders is less clear than for schizophrenia. In bipolar disorder the primary effectiveness of the mainstay treatments, lithium and anticonvulsant pharmacotherapy, is undergoing considerable revision (Bowden et al, 2000). Until this is clarified, cost-effectiveness studies are probably premature. Nevertheless the cost burden in bipolar disorder is qualitatively similar to that in schizophrenia, with in-patient costs being the primary burden and associated social costs in treated patients. The drug costs are even less than those for schizophrenia. In Chapter 5 John Cookson suggests there is little economic evidence to drive prescribing decisions. The in-patient burden does not seem to have altered with the introduction of lithium. The only drug-related study (Keck et al, 1996) showed an obvious difference in treatment costs only when lithium was compared with sodium valproate. Since these are both cheap drugs this is unlikely to influence clinical decisions. The main question is what impact... 

Benzodiazepines are the evidence-based treatment of choice for uncomplicated alcohol withdrawal.17 Barbiturates are not recommended because of their low therapeutic index due to respiratory depression. Some of the anticonvulsants have also been used to treat uncomplicated withdrawal (particularly car-bamazepine and sodium valproate). Although anticonvulsants provide an alternative to benzodiazepines, they are not as well studied and are less commonly used. The most commonly employed benzodiazepines are chlordiazepoxide, diazepam, lorazepam, and oxazepam. They differ in three major ways (1) their pharmacokinetic properties, (2) the available routes for their administration, and (3) the rapidity of their onset of action due to the rate of gastrointestinal absorption and rate of crossing the blood-brain barrier. 

A large and growing number of older people across the world suffer from schizophrenia. Recommendations for their treatment are largely based on data extrapolated from studies of the use of antipsychotic medications in younger populations. In addition most manufacturers of such medications recommend prescription of reduced doses to the elderly. The evidence base for these assumptions is unclear and raises obvious questions regarding the appropriateness of such prescribing practice. 

More studies are needed to address the insufficient evidence base for drug treatment of psychiatric disorders in pediatric patients. Recent initiatives, in particular the FDAMA 1997 and the 1998 Pediatric Rule, have provided the FDA with tools for stimulating research in this area. As a result of these initiatives, several clinical... 

Virtually all anticonvulsants are or have been of interest for the treatment of bipolar disorder. However, the importance of controlled data cannot be understated. For example, gabapentin, an anticonvulsant that initially received much attention as a potential mood stabilizer, was compared with placebo and did not appear to stabilize mood (Frye et al. 2000 Pande et al. 2000). Similar negative results were seen with topiramate in placebo-controlled trials for the treatment of mania. Although these medications might be useful adjuncts in some patients, given the currently expanded pharmacopoeia of medications with positive controlled trial data in bipolar disorder, we do not recommend the primary use of agents that have only case reports as an evidence base or controlled studies with predominantly negative results. 

An attempt has been made to discuss the position of drug therapy of various types of mental disorders within a wider perspective, and especially to clarify the relationship between drug therapy and non-drug treatments. It was necessary to deal separately with the various classes of psychopharmaceuticals and the disorders treated with them, and for our purposes it was also sensible to refer as far as possible to controlled, i.e. comparative, studies. The drawback of this evidence-based approach is obvious comparative studies of therapeutic procedures almost necessarily favor one of the compared treatments because they can never be carried out with completely identical preconditions for all treatments (Elkin et studies comparing psychotherapy with pharmacotherapy were scrutinized and discovered to include studies that were not entirely blind, random, controlled or of high quality, leading to inaccurate conclusions. Thus, meta-analyses based on flawed studies are clearly inadequate for the establishment of treatment guidelines (Klein, 2000). On the other hand, the value of an admittedly incomplete summary such as presented here is that results obtained in different places by different authors with different preconditions can be critically compared and related one to the other. 

Some evidence based on MRI studies suggests that long-term treatment with clozapine may increase basal ganglia volume (187). The significance of this finding is unknown, including any relationship to the development of tardive dyskinesia. 

Concerning the relative stabilities of the two forms, we have already seen (Section IV) that the two tautomers are probably of comparable intrinsic stability. Without forgetting the difficulties of drawing conclusions about relative stabilities from studies of chemical reactivity, it may nevertheless be added that this situation is to some extent corroborated by chemical evidence indicating, for example, the formation in almost equal amounts of 7- and 9-acetylpurine on treatment of the base under appropriate conditions with acetic anhydride, the 7 position being slightly favored.165 The explanation... 

Randomized controlled studies have not been perfiarmed for Acanthamoeba treatments because of the difficulty in recruiting a sufficient number of cases within a given time frame. Evidence-based information is scant, because many of the reports have been in the form of single case reports, studies of small numbers of patients, or retrospective reviews of patient records. 

It should be noted that a recent, evidence-based, systematic review of published randomized clinical trials of therapy for toxoplasmic retinochoroiditis fitund only three studies that met the authors criteria for inclusion, two of which were carried out more than 35 years ago. Based on this evaluation the authors concluded that there was a lack of evidence to support routine antibiotic treatment for ocular toxoplasmosis, finding no evidence for a beneficial effect on the duration and severity of signs of the disease process. However, the preponderance of evidence supports the concept that appropriate antibiotic therapy is a community standard of care, which is bolstered by guidelines for treatment in many published sources, plus the responses of those practitioners recently surveyed about their preferred patterns of management of the condition. 

Evidence-based Cardiovascular Medicine. Amsterdam Elsevier. Quarterly. ISSN 1361-2611. Reviews published studies on cardiovascular research and treatment. 

Published Guidelines and Treatment Protocols. Currently there are no published evidence-based studies that compare different agents and combination therapies for the treatment of acute mania, mixed... 

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