Post 4
Links are given to online full text resources, all other materials can be obtained via the Fade Library, just mail your request to library.services@fade.nhs.uk
Latest Systematic Reviews
Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials
Background: Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. Methods: We sought all relevant randomised controlled trials (RCTs) comparing chlorpromazine with placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. Results: Fifty RCTs from 1955-2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n=1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n=945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n=1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n=1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. Conclusions: It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Paradoxically, low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations.
Latest Technology Assessments and Appraisals
Review decision: NICE Technology Appraisal Guidance No.47, glycoprotein IIb/IIIa inhibitors in the treatment of acute coronary syndromes
Review decision: NICE Technology Appraisal Guidance No.39, the use of nicotine replacement therapy (NRT) and bupropion for smoking cessation
Review decision: NICE Technology Appraisal Guidance No.2, on the selection of prosthesis for total hip replacement and no.44, on metal-on-metal hip resurfacing.
Review/Proposal: Review of NICE Technology Appraisal Guidance No.49, ultrasound locating devices for placing central venous catheters: Proposal to move guidance to the static list
Review decision: NICE Technology Appraisal Guidance No.41 Routine anti-d prophylaxis in Rh-ve women
Review decision: NICE Technology Appraisal Guidance No.58 zanamivir, oseltamivir and amantadine for the treatment of influenza. Proposal to move guidance to the static list
Review decision: NICE Technology Appraisal Guidance No.66, olanzapine and valproate semisodium in the treatment of acute mania associated with bipolar I disorder
TA93 Colorectal cancer (advanced) - irinotecan, oxaliplatin and raltitrexed (review) - Guidance
Latest Reports
The Prevention of Venous Thromboembolism in Hospitalised Patients. 2nd Report of the Health Select Commitee, 2005. HC 99
The Health Select Committee states in its 2nd report for 2005 that each year over 25,000 people in England die from venous thromboembolism (VTE) contracted in hospital. The Committee suggests that guidelines being prepared by NICE are extended to cover all hospital patients and that new admissions are screened to assess the risk of VTE developing.
Developing an effective market regulatory framework in healthcare
An effective regulatory framework is key to delivering system reform and to
creating a well-functioning healthcare market in England, in which service
targets are achieved within budget constraints. This discussion paper offers perspectives on the development of such a framework by:
provide essential services or goods (eg water and gas
healthcare system.
Latest Hot Topics
Commissioning a patient-led NHS
Hitting the Headlines - Evidence Behind the Press Stories
Infliximab for psoriasis
An anti-inflammatory drug has proved effective for the treatment of moderate-to-severe psoriasis, reported two newspapers (14 October 2005). The reasonably accurate reports were based on the results of a well-conducted trial which found significant improvements in the psoriasis symptoms in patients receiving the drug infliximab compared to placebo.
Two newspaper articles (1,2) reported on the results of a trial assessing the effectiveness of the anti-inflammatory drug infliximab (marketed as Remicade) for the skin condition psoriasis. Both articles stated that treatment with infliximab had excellent results in improving the symptoms of the patients in the trial.
The newspaper articles were based on the results of a randomised controlled trial which was published in The Lancet (3). The trial compared the improvement in psoriasis symptoms of people receiving infliximab or a placebo (dummy drug). All of the participants included in the trial had moderate-to-severe plaque psoriasis, for the duration of at least six months. The participants receiving infliximab experienced significant improvements compared to those receiving placebo after 10 weeks of the trial. These improvements were maintained throughout the trial which lasted a year.
The newspaper articles were generally accurate summaries of the results of this well designed and conducted trial. However, it is not clear how applicable the results would be to patients with less severe forms for psoriasis. One newspaper stated that the drug has just been licensed for the treatment of psoriasis and now awaits assessment by the National Institute for Health and Clinical Excellence (NICE).
Evaluation of the evidence base for infliximab induction and maintenance therapy for moderate-to-severe psoriasis
Where does the evidence come from?
This multi-centre trial was led by Professor Christopher Griffiths from the Dermatology Centre, Hope Hospital, Salford, UK on behalf of the EXPRESS study investigators. The study was funded by Centocor (the manufacturer of infliximab) and Schering-Plough (responsible for marketing infliximab in Europe). For the study, Centocor staff collected the data, conducted the statistical analysis and participated in the preparation of the paper.
What were the authors' objectives?
The aim of the trial was to investigate the efficacy and safety of infliximab in the treatment of individuals with moderate-to-severe plaque psoriasis.
What was the nature of the evidence?
This was a multi-centre, double-blind, randomised controlled trial (RCT). A total of 378 patients were randomised to receive either infliximab (n=301) or a placebo (n=77). Patients included in the trial had had a diagnosis of moderate-to-severe psoriasis for at least six months, with at least 10% of their total body surface area affected by psoriasis. All other treatments for psoriasis were stopped before starting study treatment and were not allowed until the end of the study (except hydrocortisone applied topically to the face and/or groin after week 10).
The main objective of the trial was to assess the proportion of patients experiencing at least a 75% improvement in psoriasis symptoms (as measured with the PASI system) from baseline to week 10. Other outcomes included: patients achieving at least 75% improvements at week 24; patients achieving 50% and 90% improvement from baseline to week 10 and 24 (again using the PASI system); percentage improvement in NAPSI at weeks 10 (nail psoriasis severity index), and the proportion of patients with either cleared or minimal psoriasis at week 10. Patients were assessed at each study visit until week 50 by clinicians who did not know what treatment the patients were receiving.
What interventions were examined in the research?
Patients were randomised to either infliximab (5mg/kg as intravenous infusions at weeks 0, two and six and then every eight weeks until week 46) or a placebo. Patients receiving the placebo infusions were crossed over to receive infliximab from weeks 24 onwards.
What were the findings?
After 10 weeks, 80% of the patients receiving infliximab experienced improvements of at least 75% in their psoriasis compared to 3% of the patients receiving placebo. This finding remained statistically significant at week 24, with 82% of patients receiving infliximab experiencing improvements of at least 75% compared to 4% of patients in the placebo group. The patients receiving infliximab also experienced statistically significant improvements of at least 50% and 90% compared to those receiving placebo at weeks 10 and 24. Complete clearing of the skin was experienced by 26% of patients receiving infliximab compared to no patients receiving placebo. The numbers of adverse events were similar in both treatment groups.
What were the authors' conclusions?
The authors concluded that infliximab is an effective treatment for moderate-to-severe psoriasis. The benefits of infliximab were generally well-maintained throughout the one year trial.
How reliable are the conclusions?
This was a well-designed and conducted RCT. The study design and methods used to randomise patients to treatment and to analyse the results were appropriate. The investigators, study site personnel and patients were not aware which treatment was being received. The results presented and the authors' conclusions are therefore likely to be reliable.
'Beta blockers 'raise stroke risk''
Beta blockers increase the risk of stroke compared with other blood pressure drugs, reported the Daily Mail (18 October 2005). Although this report was accurate, it was based on a review with methodological weaknesses, so the findings should be treated with some caution.
The Daily Mail reported on 18 October 2005 (1) that people taking beta blockers have a 16% greater risk of stroke than those on other types of blood pressure pills, in particular people taking the beta blocker atenolol have a 26% higher risk of stroke than those on other medication.
The newspaper report was based on a systematic review (2) of randomised controlled trials of beta blockers for treating primary hypertension. The review found that the risk of stroke was 16% higher with beta blockers compared to other antihypertensive drugs. When the six trials of the beta blocker atenolol were analysed separately, the risk of stroke was found to be 26% higher compared to other antihypertensive drugs.
The newspaper reported the results of the review accurately. Caution was advised in changing medication based on the review findings, which is appropriate given the methodological weaknesses of the review. It should be noted that beta blockers were found to reduce the risk of stroke compared with placebo or no treatment.
Evaluation of the evidence base for beta blockers and an increased risk of stroke
Where does the evidence come from?
The evidence comes from research led by Prof LH Lindholm, based in the Department of Public Health and Clinical Medicine at Umea University Hospital, Sweden. The study was supported by a research grant from the County of Vasterbotton, Sweden. The sponsor had no role in the design or conduct of the study, or in writing the report.
What were the authors' objectives?
The objective was to analyse the effect of different beta blockers, in particular atenolol, on stroke, myocardial infarction and mortality of all causes in patients with primary hypertension.
What was the nature of the evidence?
The study was a systematic review of randomised controlled trials of beta blockers for the treatment of primary hypertension. Thirteen trials (involving 105,951 participants) that compared beta blockers with other antihypertensive drugs were included in the review, along with seven trials (27,433 participants) that compared beta blockers with placebo or no treatment.
What interventions were examined in the research?
The intervention of interest was beta blockers, which had to be received as the first-line antihypertensive drug by at least 50% of participants in the treatment group for the study to be eligible for the review. These could be compared to other antihypertensive drugs, placebo or no treatment. Studies also had to report outcome data for all-cause mortality, cardiovascular morbidity or both.
What were the findings?
Compared to other antihypertensive drugs, the risk of stroke for participants using beta blockers was found to be 16% higher, a statistically significant difference. There was no statistically significant difference in the risk of myocardial infarction or all-cause mortality. When the six trials of the beta blocker atenolol were analysed separately, the risk of stroke was found to be 26% higher for atenolol than for other antihypertensive drugs.
For trials with a mixed beta blocker and diuretic treatment group compared to patients taking other antihypertensive drugs, results were not statistically significantly different, and for trials of beta blockers other than atenolol, there were insufficient clinical events for conclusions to be drawn.
Compared to placebo or no treatment, beta blockers were found to statistically significantly reduce the risk of stroke by 19%.
What were the authors' conclusions?
Use of beta blockers to treat primary hypertension is associated with a higher risk of stroke than treatment with other antihypertensive agents. Beta blockers should therefore not be first-line treatment for primary hypertension, nor reference drugs in future randomised controlled trials of hypertension.
How reliable are the conclusions?
The objective was clearly stated and the inclusion criteria well defined. The majority of trials were located in a limited literature search which may have missed some relevant studies. The quality of the included trials was not assessed, meaning potential biases due to poor methodology were not addressed. There were also differences between the included studies in treatment regime, blood pressure control and patient characteristics which were not accounted for in the analysis. The authors state this as a limitation of their study. The analysis from which authors' conclusions were drawn combined all trials comparing beta blockers with other antihypertensive medication. The results of these trials were highly variable and statistical tests suggested significant heterogeneity. Therefore pooling may have been inappropriate and the results of the analysis may not be reliable. When the different beta blocker regimes were analysed separately, the results were more consistent, suggesting this approach may be more appropriate and the results more reliable. Given there were a number of limitations to the methodology of this review, the authors' conclusions should therefore be treated with some caution.
posted by skif at 9:10 am
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