Clive E Adams

Content and quality of 2000 controlled trials in schizophrenia over 50 years

Abstract Objective To provide a comprehensive survey of the content and quality of intervention studies relevant to the treatment of schizophrenia. Design Data were extracted from 2000 trials on the Cochrane Schizophrenia Groups register. Main outcome measures Type and date of publication, country of origin, language, size of study, treatment setting, participant group, interventions, outcomes, and quality of study. Results Hospital based drug trials undertaken in the United States were dominant in the sample (54%). Generally, studies were short (54%<6 weeks), small (mean number of patients 65), and poorly reported (64% had a quality score of ≤2 (maximum score 5)). Over 600 different interventions were studied in these trials, and 640 different rating scales were used to measure outcome. Conclusions Half a century of studies of limited quality, duration, and clinical utility leave much scope for well planned, conducted, and reported trials. The drug regulatory authorities should stipulate that the results of both explanatory and pragmatic trials are necessary before a compound is given a licence for everyday use.

A systematic review of studies of depression prevalence in university students

BACKGROUND Depression is a common health problem, ranking third after cardiac and respiratory diseases as a major cause of disability. There is evidence to suggest that university students are at higher risk of depression, despite being a socially advantaged population, but the reported rates have shown wide variability across settings. PURPOSE To explore the prevalence of depression in university students. METHOD PubMed, PsycINFO, BioMed Central and Medline were searched to identify studies published between 1990 and 2010 reporting on depression prevalence among university students. Searches used a combination of the terms depression, depressive symptoms, depressive disorders, prevalence, university students, college students, undergraduate students, adolescents and/or young adults. Studies were evaluated with a quality rating. RESULTS Twenty-four articles were identified that met the inclusion and exclusion criteria. Reported prevalence rates ranged from 10% to 85% with a weighted mean prevalence of 30.6%. CONCLUSIONS The results suggest that university students experience rates of depression that are substantially higher than those found in the general population. Study quality has not improved since 1990.

Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine

Objective To compare the effect of intramuscular olanzapine with intramuscular haloperidol plus promethazine on rapid tranquillisation of agitated or violent people with mental illness. Design Pragmatic, allocation concealed, randomised controlled trial. Setting Emergency services of a general hospital psychiatry department in Vellore, south India. Participants 300 adults with agitated or violent behaviour as a result of mental illness; 150 randomised to intramuscular olanzapine and 150 randomised to intramuscular haloperidol plus promethazine. Interventions Open treatment with intramuscular olanzapine or intramuscular haloperidol plus promethazine. Main outcome measures Primary outcome was proportion of patients who were tranquil or asleep at 15 minutes and 240 minutes. Secondary outcomes were proportion of patients who were tranquil, asleep, restrained, absconding, or clinically improved at 15, 30, 60, 120, and 240 minutes; additional medical interventions and adverse effects over four hours; and compliance with oral drugs and adverse effects over two weeks. Results Of 300 people randomised to receive either intramuscular olanzapine or intramuscular haloperidol plus promethazine, follow-up data were available for primary outcomes for 298 (99%). Both treatments resulted in similar proportions of people being tranquil or asleep at 15 minutes (olanzapine 131/150 (87%), haloperidol plus promethazine 136/150 (91%); relative risk 0.96, 95% confidence interval 0.34 to 1.47) and 240 minutes (olanzapine 144/150 (96%), haloperidol plus promethazine 145/150 (97%); relative risk 0.99, 0.95 to 1.03). However, more people given olanzapine than those given haloperidol plus promethazine required additional drugs over four hours (65/150 (43%) v 31/150 (21%); relative risk 2.07, 1.43 to 2.97). Adverse effects were uncommon with both treatments. Conclusions Intramuscular olanzapine and intramuscular haloperidol plus promethazine were effective at rapidly tranquillising or sedating agitated or violent patients with mental illness but the combination resulted in fewer additional medical interventions within four hours of intervention. Trial registration Clinical trials NCT00455234.

An investigation of the adequacy of MEDLINE searches for randomized controlled trials (RCTs) of the effects of mental health care.

Valid reviews of the effects of mental health care depend on identifying as high a proportion as possible of relevant randomized controlled trials (RCTs). To investigate the sensitivity and precision both of MEDLINE and of hand-searching for RCTs in mental health, 12 journals specializing in mental health and indexed by the National Library of Medicine (NLM) for MEDLINE were searched for the years 1971, 1976, 1981, 1986 and 1991. The sensitivity of the hand-search was 94% (95% Confidence Interval (CI) 93-95%), but it had a precision of only 7% (CI 6-8%). The optimal MEDLINE search had a sensitivity of only 52% (CI 48-56%) and a precision of 59% (CI 55-63%). Of the reports of RCTs identified by the hand-search, 9% (CI 7-11%) were not included in MEDLINE at all. Authors had included methodological descriptions in 84% (CI 80-88%) of RCTs found by the hand-search but missed by the MEDLINE search. Systematic reviews of mental health care which are based solely on MEDLINE searches of the literature will miss a large proportion of the relevant RCTs, and are thus liable to random error and bias. A register of mental health RCTs is urgently required.

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project: a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification

BackgroundMany opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares dihydrocodeine with buprenorphine.MethodsOpen label, pragmatic, randomised controlled trial in a large remand prison in the North of England. Ninety adult male prisoners requesting an opiate detoxification were randomised to receive either daily sublingual buprenorphine or daily oral dihydrocodeine, given in the context of routine care. All participants gave written, informed consent. Reducing regimens were within a standard regimen of not more than 20 days and were at the discretion of the prescribing doctor. Primary outcome was abstinence from illicit opiates as indicated by a urine test at five days post detoxification. Secondary outcomes were collected during the detoxification period and then at one, three and six months post detoxification. Analysis was undertaken using relative risk tests for categorical data and unpaired t-tests for continuous data.Results64% of those approached took part in the study. 63 men (70%) gave a urine sample at five days post detoxification. At the completion of detoxification, by intention to treat analysis, a higher proportion of people allocated to buprenorphine provided a urine sample negative for opiates (abstinent) compared with those who received dihydrocodeine (57% vs 35%, RR 1.61 CI 1.02–2.56). At the 1, 3 and 6 month follow-up points, there were no significant differences for urine samples negative for opiates between the two groups. Follow up rates were low for those participants who had subsequently been released into the community.ConclusionThese findings would suggest that dihydrocodeine should not be routinely used for detoxification from opiates in the prison setting. The high relapse rate amongst those achieving abstinence would suggest the need for an increased emphasis upon opiate maintenance programmes in the prison setting.Trial registrationCurrent Controlled Trials ISRCTN07752728

Five large Chinese biomedical bibliographic databases: accessibility and coverage

BACKGROUND Much biomedical research is now undertaken in China. METHODS Five large biomedical databases originating from China (CBM, CMCC, CNKI, VIP and WANFANG) are described and their utility and accessibility investigated. RESULTS These databases index 2500 journals largely not familiar to MEDLINE users. Free access, search features, record selection, ease of downloading and cost of subscription varies considerably between databases. CONCLUSION Searches in all databases benefit from the use of simplified Chinese and all provide links to full text articles. Less than 6% of the 2500 journals in the five databases were listed as being indexed for MEDLINE.

Factors associated with the use of physical restraints for agitated patients in psychiatric emergency rooms.

OBJECTIVE To examine factors associated with physical restraint in psychiatric emergency rooms. METHOD We extracted variables likely to predict use of physical restraints from a large randomised trial undertaken in three psychiatric emergency rooms in Rio de Janeiro. We fitted a Bayesian binary multivariate model using only variables clearly preceding the restraints. RESULTS Of 301 agitated, aggressive people admitted to emergency rooms, 73 (24%) were restrained during the first 2 h of admission. In Rio, younger people (OR=1.03 for each year younger), exhibiting intense (OR=2.53) or extreme agitation (OR=7.71), thought to result from substance misuse (OR=1.75) or diagnoses other than psychosis (OR=1.88), arriving in the morning (OR=1.64) were at greater risk of physical restraints than older, less severely aggressive or agitated people, arriving at the hospital during the afternoon or night. Hospital, gender, first admission to hospital and medication were not associated with risk of being restrained. CONCLUSION Restraint practices in Rio are predictable and based on a limited clinical assessment. Predictive factors for physical restraint may vary worldwide, but should be monitored and studied to assist training, and to establish programs to evaluate and refine this controversial practice.

Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study

BackgroundThe medical management of aggressive and violent behaviour is a critical situation for which there is little evidence. In order to prepare for a randomised trial, due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001, a survey of current practice was necessary.MethodsA seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro, Brazil.ResultsIn one hospital data were not available. Of the 764 people with psychosis attending these ERs, 74 were given IM medication for rapid tranquillisation (9.7%, 2.1/week/100,000). A haloperidol-promethazine mix (with or without other drugs) was used for the majority of patients (83%).ConclusionThe haloperidol-promethazine mix, given intramuscularly for rapid tranquilization, is prevalent in Rio, where it is considered both safe and efficient. However, scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a randomized trial of IM haloperidol-promethazine is overdue.

Systematic overview of Cochrane reviews for anticholinergic effects of antipsychotic drugs.

Background: Despite much being written on the topic, there are few surveys investigating the prevalence of anticholinergic adverse effects of antipsychotic drugs. One study, however, used trial-derived data to calculate estimates. Objectives: To investigate the prevalence/incidence rates of anticholinergic effects as viewed from within relevant randomized trials. Methods: Data were extracted from each relevant study included in Cochrane reviews. Data were checked, extracted, and simple frequencies, and 95% confidence intervals (CIs) were calculated. Results: Many trials in relevant reviews reported no data on anticholinergic effects (estimate 40,000 participants). However, data were extracted from 177 studies within 54 reviews (N = 27,328 participants). Most data are short-term (<12 weeks). For blurred vision, the newer generations of drugs have rates of between 10% and 20% (eg, risperidone, n = 1460, 6 randomized controlled trials [RCTs], 11.9% prevalence; CI, 10-14; olanzapine, n = 1584; 4 RCTs, 12.2% prevalence; CI, 11-14). These estimates are similar to those of sulpiride (n = 186; 2 RCTs, 12.4%; CI, 8-18) and chlorpromazine (n = 294; 10 RCTs, 11.2%; CI, 8-15), less than trifluoperazine (n = 167; 8 RCTs, 31.1%; CI, 25-39), but considerably more than perphenazine (n = 410; 8 RCTs, 3.7%; CI, 2-6). Data are presented on a range of anticholinergic effects across different periods. Conclusions: Anticholinergic symptoms are common adverse effects associated with the use of all antipsychotic drugs, and newer-generation drugs are not clearly distinguishable from many older compounds. Adverse effect data should be more accessible.

Assessment of adverse effects in clinical studies of antipsychotic medication: survey of methods used

BACKGROUND Clinical studies of antipsychotic medication are a primary source of data on the nature of, and relative liability for, adverse effects, relevant to prescribing decisions in clinical practice. AIMS To identify how safety and tolerability data were collected and reported in recent clinical studies of antipsychotics. METHOD A survey was conducted of all 167 eligible studies published between 2002 and 2007 on the Cochrane Schizophrenia Group register. RESULTS Extrapyramidal side-effects (EPS) and weight gain were most frequently assessed. A minority of reports addressed metabolic abnormalities, aversive subjective experiences and sexual dysfunction. Published rating scales were frequently used to evaluate EPS, but systematic methods were rarely applied to other treatment-emergent problems. The definition of individual adverse effects and the manner of reporting were inconsistent. CONCLUSIONS The way in which safety and tolerability data are collected and reported in clinical studies does not allow for fair and meaningful comparison of the relative risk profiles of individual antipsychotic drugs.