Treatment of tardive dyskinesia with galantamine: a randomized controlled crossover trial. Tailoring systematic reviews to meet critical priorities in maternal health in the intrapartum period. A double-blind comparison of clonazepam and placebo in the treatment of neuroleptic-induced akathisia. The effectiveness of interventions to change six health behaviours: a review of reviews. Low-dose mirtazapine: a new option in the treatment of antipsychotic-induced akathisia. A randomized, double-blind, placebo- and propranolol-controlled trial. Propranolol as a primary treatment of neuroleptic-induced akathisia. The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia. Are there schizophrenics for whom drugs may be unnecessary or contraindicated? A placebo-controlled trial of nadolol in the treatment of neuroleptic-induced akathisia. Quality of reporting of randomized controlled trials in general endocrinology literature. Educating physicians to reduce benzodiazepine use by elderly patients: a randomized controlled trial.
Recent evidence suggests that tar-dive dyskinesia may result from antipsychotic-induced damage to striatal cholinergic neurons. To test whether cholinesterase inhibitors compensate for diminished cholinergic activity, we conducted a 30-week randomized, double-blind, placebo-controlled crossover trial of galantamine in patients with tardive dyskinesia.
                Patients with tardive dyskinesia were recruited between June 2001 and June 2004. After a 2-week baseline period, 35 male schizophrenia patients, on stable doses of antipsychotics, were randomly assigned to receive galantamine (8-24 mg) or placebo for two 12-week phases separated by a 4-week washout period. Patients were evaluated every 2 weeks for changes in extrapyramidal symptoms and before and after each treatment for effects on psychiatric symptoms and cognition.
                Galantamine reduced mean total Abnormal Involuntary Movement Scale (AIMS) scores more than placebo, but this difference was not statistically significant (p = .08). However, patients initially randomly assigned to galantamine showed a reversal of AIMS scores after switching to placebo. Simpson-Angus Scale ratings of parkinsonism were significantly higher with galantamine than placebo (p = .0005) and correlated with age. There were no significant differences between groups in akathisia, cognition, or psychiatric symptoms. More patients dropped out while receiving galantamine, but this outcome did not significantly influence the results.
                In contrast to previous reports, reductions in tardive dyskinesia associated with galantamine were not statistically significant compared with placebo in this trial. However, galantamine was associated with a modest rebound in dyskinesia scores after discontinuation and clinically minor but statistically higher ratings of parkinsonism. These findings support the need for further investigations of cholinergic mechanisms underlying tardive dyskinesia and extrapyramidal effects of cholinesterase inhibitors when used in combination with antipsychotics in susceptible patients.
                ClinicalTrials.gov identifier NCT00164242. Health care practitioners and researchers commonly call for greater reliance on evidence as a means to achieve improvement in quality of care. Systematic reviews provide a means to accelerate the use of evidence-based clinical interventions and public health practices. The extent to which these time- and resource-intensive systematic reviews currently address critical maternal health priorities in the intrapartum period is unclear. This analysis summarises key maternal health and research priorities, maps these priorities to existing reviews, identifies gaps in the literature that can be addressed with systematic reviews, and highlights key methodological concerns in conducting systematic reviews. The analysis draws on published data on maternal morbidities and an overview of 108 systematic reviews in Medline in the past 5 years using the MeSH terms 'Delivery, Obstetric,' to draw the links between health priorities, research priorities, existing evidence and missing evidence. Key causes of morbidity during labour and delivery in the United States include haemorrhage, pre-eclampsia and eclampsia, obstetric trauma and infection. Analyses of maternal morbidity and mortality suggest that key concerns include racial and ethnic disparities in health outcomes and the prevention of adverse events. Systematic reviews, however, generally tend to focus on the reduction of harms associated with interventions, are frequently limited to randomised designs, and do not address issues of health disparities. The results suggest that advances in evidence-based care in maternal health require that systematic reviews address issues of prevention of adverse events, include a larger variety of study designs when necessary and pay closer attention to health disparities. The present study was designed to investigate the efficacy of clonazepam in neuroleptic-induced akathisia. Twelve patients were treated during 2 weeks with clonazepam or placebo in a double-blind randomized design. Akathisia was scored by an independent rater before and after treatment, as well as 1 week after medication withdrawal. Clonazepam (0.5-2.5 mg/day) induced a significantly higher reduction in the akathisia scores than placebo (p < 0.05). One week after stopping the drug, there was a partial but significant relapse in the treated group as compared with controls, in whom the symptoms remained stable. In addition, the clinical improvement was significantly correlated with the daily dose of clonazepam (rs = 0.827; p < 0.002). These results support the potential usefulness of clonazepam in the treatment of neuroleptic-induced akathisia and suggest an optimal daily dose in the range of 10-40 micrograms/kg. Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e.g. for drug or alcohol dependency).
                The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis.
                We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e.g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e.g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours.Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities.
                Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed. Preliminary evidence indicates a beneficial effect of serotonin 2A (5-HT(2A)) receptor antagonists in antipsychotic-induced akathisia (AIA). We investigated the antiakathisia effect, safety, and tolerability of low-dose mirtazapine, an agent with marked 5-HT(2A) antagonism.
                In a 7-day double-blind trial, 90 antipsychotic-treated patients meeting DSM-IV criteria for AIA were randomly assigned to mirtazapine (n = 30; 15 mg), propranolol (n = 30; 80 mg), or placebo (n = 30). Primary outcome measures were between-group differences in Barnes Akathisia Scale (BAS) global scores and in the proportion of responders (reduction of > or = 2 points on BAS). Analysis was by intention to treat.
                Twenty-four patients (26.6%) who were assigned treatment did not complete the study (7 mirtazapine, 8 propranolol, 9 placebo), due to lack of response (n = 19) and adverse events (n = 5). Both mirtazapine and propranolol significantly reduced AIA severity (BAS: -34% mirtazapine and -29% propranolol vs. placebo -11%; p = .012 and p = .023, respectively). Thirteen (43.3%) mirtazapine and 9 (30.0%) propranolol-treated patients versus 2 (6.7%) placebo-treated patients responded (the corresponding odds ratios 10.7 [95% confidence interval (CI), 2.1-53.3] and 6.0 [95% CI, 1.1-30.7]). Five (16.7%) of 30 propranolol-treated patients and none in the mirtazapine and placebo groups (p = .0195 for both) prematurely discontinued the study due to clinically significant hypotension or bradycardia.
                The comparable efficacy and better tolerability of low-dose mirtazapine versus propranolol, the current first-line treatment for AIA, position mirtazapine as a favorable candidate for the treatment of acute AIA and may improve current therapeutic practices. We conducted a randomized, double-blind clinical trial of propranolol versus placebo as a single treatment of neuroleptic-induced akathisia in eleven schizophrenic patients. Neither propranolol nor placebo treated patients showed a significant improvement in akathisia. While propranolol may be useful as an adjunct to anticholinergic medication in the treatment of neuroleptic-induced akathisia, propranolol does not appear to be effective within 48 hours as a primary treatment in a select group of schizophrenic patients. Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design.
                To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone.
                Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted.
                66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure.
                After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.
                Copyright 2003 John Wiley & Sons, Ltd. This study reports that there are schizophrenics who do relatively well long term without the routine or continuous use of antipsychotic medication. Specially selected young males undergoing an acute schizophrenic episode were followed, after hospitalization, for up to three years. While hospitalized they were assigned randomly to either placebo or chlorpromazine treatment. Many unmedicated-while-in-hospital patients showed greater long-term improvement, less pathology at follow-up, fewer rehospitalizations and better overall function in the community than patients who were given chlorpromazine while in the hospital. Factors related to post-hospital outcome were good premorbid history and short-lived paranoid characteristics. Considerations which may have an effect on the successful management of acute schizophrenic patients not on medication are mentioned. The findings underline the need for further study of how to utilize antipsychotic medication more selectively in the treatment of schizophrenia. Although propranolol has been documented to be useful in treatment of neuroleptic-induced akathisia, preliminary anecdotal reports on the efficacy of nadolol in treatment of this condition are contradictory.
                To evaluate the efficacy of nadolol in treatment of this condition, a double-blind, placebo-controlled trial was conducted in 20 psychiatric inpatients. Patients with akathisia of at least moderate severity were randomly assigned to receive nadolol 40 to 80 mg/day or placebo. Patients were rated daily for 4 days, then every other day for 15 days by means of the Extrapyramidal Symptom Rating Scale.
                No significant differences were found between or within groups in subjective restlessness scores. In objective akathisia scores, there were no significant differences between groups; however, beginning at Day 9, both groups showed significant improvement compared with Day 1. There was no difference between groups in number of responders.
                The authors' data do not support the efficacy of nadolol in the treatment of neuroleptic-induced akathisia and do not provide support for a peripheral site of action for beta-blockers in treatment of this condition. The reporting quality of randomized controlled trials (RCTs) is poor in general medicine and several areas of specialization but unknown in endocrinology.
                Our aim was to assess the reporting quality of RCTs in general endocrinology. A secondary objective was to identify predictors for better reporting quality.
                We systematically reviewed RCTs published in three general endocrinology journals between January 2005 and December 2006.
                We included parallel-design RCTs that addressed a question of treatment or prevention. Article selection and data abstraction were conducted by two reviewers independently, and disagreements were resolved by consensus.
                There were two main outcomes: 1) a 15-point overall reporting quality score (OQS) based on the Consolidated Standards for Reporting Trials (CONSORT); and 2) a 3-point key score, based on allocation concealment, blinding, and use of intention-to-treat analysis.
                Eighty nine RCTs were included. The median OQS was 10 (interquartile range = 2). Allocation concealment, blinding, and analysis by intention to treat were reported in 10, 20, and 16 of the 89 RCTs, respectively. A multivariable regression analysis showed that complete industrial funding [incidence rate ratio (IRR) = 1.014; 95% confidence interval (CI), 1.010-1.018], journal of publication (IRR = 1.068; 95% CI, 1.007-1.132), and sample size (IRR = 1.048; 95% CI, 1.026-1.070) were significantly associated with a slightly better OQS.
                The quality of RCT reporting in general endocrine literature is suboptimal. We discuss our results, highlight the areas where improvements are needed, and provide some recommendations. Benzodiazepine use by elderly patients is associated with adverse outcomes including increased risk of falls and fractures, motor vehicle accidents and cognitive impairment. Recent studies suggest that individualized feedback and education to physicians may improve drug prescribing. In this study, we evaluated an intervention to address the inappropriate prescribing of benzodiazepines for elderly patients.
                We identified 1624 primary care physicians who wrote at least 10 prescriptions for the target drugs in a 2-month period and randomly assigned these physicians to the intervention group or the control group. We obtained data from the Ontario Drug Benefit claims database, which covers all Ontario residents aged 65 years and over for drugs selected from a minimally restrictive formulary. Every 2 months for 6 months, confidential profiles of benzodiazepine prescription use coupled with evidence-based educational bulletins were mailed to the intervention group. The control group received feedback and educational bulletins about first-line antihypertension drug prescribing for elderly patients. Our main outcome measures were reductions in the proportion of each physician's total benzodiazepine prescriptions for long-acting agents, combinations of benzodiazepines with other psychoactive medications (including other benzodiazepines) and long-term benzodiazepine therapy.
                After randomization, 168 physicians agreed to be in the intervention group and 206 in the control group. Their demographic and prescribing characteristics were similar. Although the proportion of long-acting benzodiazepine prescriptions decreased by 0.7% in the intervention group between the baseline period and the end of the intervention period (from 20.3%, or a mean of 29.5 prescriptions, to 19.6%, or a mean of 27.7 prescriptions) and increased by 1.1% in the control group (from 19.8%, or a mean of 26.4 prescriptions, to 20.9%, or a mean of 27.7 prescriptions) (p = 0.036), this difference was not clinically significant. There was no significant difference over the study period in either combination prescribing of benzodiazepines or in prescriptions for long-term benzodiazepine therapy.
                We did not find that a program of confidential feedback and educational material offered to Ontario primary care physicians had a clinically significant impact on their benzodiazepine prescribing.
Over a short follow-up period, the use of benzodiazepines may reduce the symptoms of antipsychotic-induced acute akathisia. This review highlights the need for well designed, conducted and reported clinical trials to address the claims of open studies.