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The Cochrane Database of Systematic... Oct 2014Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between the various first-generation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between the various first-generation antipsychotics, however, low-potency first-generation antipsychotic drugs are sometimes perceived as less efficacious than high-potency first-generation compounds by clinicians, and they also seem to differ in their side effects.
OBJECTIVES
To review the effects of high-potency, first-generation perphenazine compared with low-potency, first-generation antipsychotic drugs for people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (October 2010).
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing perphenazine with first-generation, low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis and using a random-effects model.
MAIN RESULTS
The review currently includes four relevant randomised trials with 365 participants. The size of the included studies was between 42 and 158 participants with a study length between one and four months. Overall, the methods of sequence generation and allocation concealment were poorly reported. Most studies were rated as low risk of bias in terms of blinding. Overall, attrition bias in the studies was high.The effects of perphenazine and low-potency antipsychotic drugs seemed to be similar in terms of the primary outcome - response to treatment (perphenazine 58%, low-potency antipsychotics 59%, 2 RCTs, n = 138, RR 0.97 CI 0.74 to 1.26 - moderate quality of evidence). There was also no clear evidence of a difference in acceptability of treatment with the number of participants leaving the studies early due to any reason, however results were imprecise (perphenazine 30%, low-potency antipsychotics 28%, 3 RCTs, n = 323, RR 0.78 CI 0.35 to 1.76, very low quality of evidence).There were low numbers of studies available for the outcomes experiencing at least one adverse effect (perphenazine 33%, low-potency antipsychotics 47%, 2 RCTs, n = 165, RR 0.83 CI 0.36 to 1.95, low quality evidence) and experiencing at least one movement disorder (perphenazine 22%, low-potency first-generation antipsychotics 0%, 1 RCT, n = 69, RR 15.62 CI 0.94 to 260.49, low quality evidence), and the confidence intervals for the estimated effects did not exclude important differences. Akathisia was more frequent in the perphenazine group (perphenazine 25%, low-potency antipsychotics 22%, 2 RCTs, n = 227, RR 9.45 CI 1.69 to 52.88), whereas severe toxicity was less so (perphenazine 42%, low-potency antipsychotics 69%, 1 RCT, n = 96, RR 0.61 CI 0.41 to 0.89).There were three deaths in the low-potency group by four months but the difference between groups was not significant (perphenazine 0%, low-potency antipsychotics 2%, 1 RCT, n = 96, RR 0.14 CI 0.01 to 2.69, moderate quality evidence). No data were available for our prespecified outcomes of interest sedation or quality of life. Data were not available for other outcomes such as relapse, service use, costs and satisfaction with care.The event rates reported quote simple aggregates and are not based on the RRs.
AUTHORS' CONCLUSIONS
The results do not show a superiority in efficacy of high-potency perphenazine compared with low-potency first-generation antipsychotics. There is some evidence that perphenazine is more likely to cause akathisia and less likely to cause severe toxicity, but most adverse effect results were equivocal. The number of studies as well as the quality of studies is low, with quality of evidence for the main outcomes ranging from moderate to very low, so more randomised evidence would be needed for conclusions to be made.
Topics: Adult; Antipsychotic Agents; Humans; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 25290157
DOI: 10.1002/14651858.CD009369.pub2 -
The Cochrane Database of Systematic... Sep 2014Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic drugs, however,... (Review)
Review
BACKGROUND
Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic drugs, however, low-potency antipsychotic drugs are sometimes perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects.
OBJECTIVES
To review the effects in clinical response of flupenthixol and low-potency antipsychotics for people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (July 2010).
SELECTION CRITERIA
Randomised controlled trials that compared flupenthixol with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For continuous data, we calculated mean differences (MD) based on a random-effects model.
MAIN RESULTS
The review currently includes one randomised trial from mainland China with 153 participants that lasted two months and compared flupenthixol with chlorpromazine. The exact methods of sequence generation and allocation concealment were not reported, and medication was provided in an open manner. There were no data on the outcomes that we had a priori selected for a 'Summary of findings' table.There was no significant difference between flupenthixol and chlorpromazine in the participants' general mental state at endpoint as measured by the Brief Psychiatric Rating Scale (BPRS) total score (1 randomised controlled trial (RCT), n = 153, MD 2.20 95% confidence interval (CI) -1.25 to 5.65). Chlorpromazine was associated with significantly less dizziness (1 RCT, n = 153, MD 0.12 95% CI 0.01 to 0.23); dystonia (1 RCT, n = 153, MD 0.29 95% CI 0.13 to 0.45); unsteady gait (1 RCT, n = 153, MD 0.46 95% CI 0.28 to 0.64); reduced facial expression (1 RCT, n = 153, MD 0.27 95% CI 0.09 to 0.45); restlessness (1 RCT, n = 153, MD 0.69 95% CI 0.45 to 0.93); rigidity (elbow) (1 RCT, n = 153, MD 0.48 95% CI 0.28 to 0.68); and tremor (1 RCT, n = 153, MD 0.56 95% CI 0.34 to 0.78). Chlorpromazine produced more dryness of mouth than flupenthixol (1 RCT, n = 153, MD -0.14 95% CI -0.25 to -0.03).
AUTHORS' CONCLUSIONS
The evidence base of flupenthixol versus low-potency first-generation antipsychotics is currently restricted to one randomised comparison with chlorpromazine. The few reported data do not suggest a difference in efficacy, but flupenthixol appeared to produce more movement disorders and dizziness, while chlorpromazine was associated with the anticholinergic side effect - dryness of mouth. More trials are needed to make conclusions about the relative effects of flupenthixol and low-potency antipsychotics.
Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Chlorpromazine; Flupenthixol; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Xerostomia
PubMed: 25177834
DOI: 10.1002/14651858.CD009227.pub2 -
The Cochrane Database of Systematic... Aug 2014Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between any other antipsychotic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between any other antipsychotic compounds, however, low-potency antipsychotic drugs are often perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects. This review examined the effects of the high-potency antipsychotic fluphenazine compared to those of low-potency antipsychotics.
OBJECTIVES
To review the effects of fluphenazine and low-potency antipsychotics for people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (November 2010).
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing fluphenazine with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model.
MAIN RESULTS
The review currently includes seven randomised trials and 1567 participants that compared fluphenazine with low-potency antipsychotic drugs. The size of the included studies was between 40 and 438 participants. Overall, sequence generation, allocation procedures and blinding were poorly reported. Fluphenazine was not significantly different from low-potency antipsychotic drugs in terms of response to treatment (fluphenazine 55%, low-potency drug 55%, 2 RCTs, n = 105, RR 1.06 CI 0.75 to 1.50, moderate quality evidence). There was also no significant difference in acceptability of treatment with equivocal numbers of participants leaving the studies early due to any reason (fluphenazine 36%, low-potency antipsychotics 36%, 6 RCTs, n = 1532, RR 1.00 CI 0.88 to 1.14, moderate quality evidence). There was no significant difference between fluphenazine and low-potency antipsychotics for numbers experiencing at least one adverse effect (fluphenazine 70%, low-potency antipsychotics 88%, 1 RCT, n = 65, RR 0.79 CI 0.58 to 1.07, moderate quality evidence). However, at least one movement disorder occurred significantly more frequently in the fluphenazine group (fluphenazine 15%, low-potency antipsychotics 10%, 3 RCTs, n = 971, RR 2.11 CI 1.41 to 3.15, low quality of evidence). In contrast, low-potency antipsychotics produced significantly more sedation (fluphenazine 20%, low-potency antipsychotics 64%, 1 RCT, n = 65, RR 0.31 CI 0.13 to 0.77, high quality evidence). No data were available for the outcomes of death and quality of life. The results of the primary outcome were robust in a number of subgroup and sensitivity analyses.Adverse effects such as akathisia (fluphenazine 15%, low-potency antipsychotics 6%, 5 RCTs, n = 1209, RR 2.28 CI 1.58 to 3.28); dystonia (fluphenazine 5%, low-potency antipsychotics 2%, 4 RCTs, n = 1309, RR 2.66 CI 1.25 to 5.64); loss of associated movement (fluphenazine 20%, low-potency antipsychotics 2%, 1 RCT, n = 338, RR 11.15 CI 3.95 to 31.47); rigor (fluphenazine 27%, low-potency antipsychotics 12%, 2 RCTs, n = 403, RR 2.18 CI 1.20 to 3.97); and tremor (fluphenazine 15%, low-potency antipsychotics 6%, 2 RCTs, n = 403, RR 2.53 CI 1.37 to 4.68) occurred significantly more frequently in the fluphenazine group.For other adverse effects such as dizziness (fluphenazine 8%, low-potency antipsychotics 17%, 4 RCTs, n = 1051, RR 0.49 CI 0.32 to 0.73); drowsiness (fluphenazine 18%, low-potency antipsychotics 25%, 3 RCTs, n = 986, RR 0.67 CI 0.53 to 0.86); dry mouth (fluphenazine 11%, low-potency antipsychotics 18%, 4 RCTs, n = 1051, RR 0.63 CI 0.45 to 0.89); nausea (fluphenazine 4%, low-potency antipsychotics 15%, 3 RCTs, n = 986, RR 0.25 CI 0.14 to 0.45); and vomiting (fluphenazine 3%, low-potency antipsychotics 8%, 3 RCTs, n = 986, RR 0.36 CI 0.18 to 0.72) results favoured fluphenazine with significantly more events occurring in the low-potency antipsychotic group for these outcomes.
AUTHORS' CONCLUSIONS
The results do not show a clear difference in efficacy between fluphenazine and low-potency antipsychotics. The number of included studies was low and their quality moderate. Therefore, further studies would be needed to draw firm conclusions about the relative effects of fluphenazine and low-potency antipsychotics.
Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Dyskinesia, Drug-Induced; Fluphenazine; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 25087165
DOI: 10.1002/14651858.CD009230.pub2 -
The Cochrane Database of Systematic... May 2014Pericyazine is a 3-cyano-10 (3-4'-hydroxypiperidinopropyl) phenothiazine. It is overall pharmacologically similar with chlorpromazine, though particularly sedating.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pericyazine is a 3-cyano-10 (3-4'-hydroxypiperidinopropyl) phenothiazine. It is overall pharmacologically similar with chlorpromazine, though particularly sedating. Dopamine receptor subtype analysis has not been performed for pericyazine, but the drug appears to induce greater noradrenergic than dopaminergic blockade. Compared to chlorpromazine, pericyazine reportedly has more potent antiemetic, antiserotonin, and anticholinergic activity.
OBJECTIVES
To evaluate the clinical effects and safety of pericyazine in comparison with placebo, typical and atypical antipsychotic agents and standard care for people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (February 2013) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials.
SELECTION CRITERIA
All relevant randomised controlled trials focusing on pericyazine for schizophrenia and other types of schizophrenia-like psychoses (schizophreniform and schizoaffective disorders). We excluded quasi-randomised trials.
DATA COLLECTION AND ANALYSIS
Data were extracted independently from included papers by at least two review authors. Risk ratios (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data were calculated. We assessed risk of bias for included studies and used GRADE to judge quality of evidence.
MAIN RESULTS
We could only include five studies conducted between 1965 and 1980. Most of the included studies did not report details of randomisation, allocation concealment, details of blinding and we could not assess the impact of attrition due to poor reporting.For the primary outcome of Global state - not improved, the confidence interval was compatible with a small benefit and increased risk of not improving with pericyazine compared with typical antipsychotics (2 RCTs, n = 122, RR 1.24 CI 0.93 to 1.66, very low quality of evidence) or atypical antipsychotics (1 RCT, n = 93, RR 0.97 CI 0.67 to 1.42, very low quality of evidence).When compared with typical antipsychotics relapse was only experienced by one person taking pericyazine (1 RCT, n = 80, RR 2.59 CI 0.11 to 61.75, very low quality of evidence).Pericyazine was associated with more extrapyramidal side effects than typical antipsychotics (3 RCTs, n = 163, RR 0.52 CI 0.34 to 0.80, very low quality of evidence) and atypical antipsychotics (1 RCT, n = 93, RR 2.69 CI 1.35 to 5.36, very low quality of evidence).The estimated risk of leaving the study early for specific reasons was imprecise for the comparisons of pericyazine with typical antipsychotics (2 RCTs, n = 71, RR 0.46 CI 0.11 to 1.90, very low quality of evidence), and with atypical antipsychotics (1 RCT, n = 93, RR 0.13 CI 0.01 to 2.42, very low quality of evidence).
AUTHORS' CONCLUSIONS
On the basis of very low quality evidence we are unable to determine the effects of pericyazine in comparison with typical or atypical antipsychotics for the treatment of schizophrenia. However, there is some evidence that pericyazine may be associated with a higher incidence of extrapyramidal side effects than other antipsychotics, and again this was judged to be very low quality evidence. Large, robust studies are still needed before any firm conclusions can be drawn.
Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Humans; Phenothiazines; Randomized Controlled Trials as Topic; Schizophrenia; Spasm; Tremor
PubMed: 24825770
DOI: 10.1002/14651858.CD007479.pub2 -
The Cochrane Database of Systematic... Jan 2014Perazine is an old phenothiazine derivative used for the treatment of people with schizophrenia and is reputed to have a low level of extrapyramidal adverse effects. As... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perazine is an old phenothiazine derivative used for the treatment of people with schizophrenia and is reputed to have a low level of extrapyramidal adverse effects. As far as we are aware, its use is limited to Germany, Poland, the former Yugoslavia and the Netherlands.
OBJECTIVES
To examine the effects of perazine for those with schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medications.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register, which includes relevant randomised controlled trials from the bibliographic databases Biological Abstracts, CINAHL, The Cochrane Library, EMBASE, MEDLINE, PsycLIT, LILACS, PSYNDEX, Sociological Abstracts and Sociofile. We searched the references of all included studies for further trials. We contacted pharmaceutical companies and authors of trials. We updated this search on 16th July 2012.
SELECTION CRITERIA
We selected all randomised controlled trials that compared perazine with other treatments for people with schizophrenia or schizophrenia-like psychoses, or both.
DATA COLLECTION AND ANALYSIS
The review authors (SL, BH, BHe) independently inspected the citations and where possible abstracts and ordered papers for re-inspection and quality assessment. We independently extracted data. We calculated the risk ratio (RR) and 95% confidence interval (CI) using a random-effects model. For continuous data, we calculated mean differences (MD). We inspected all data for heterogeneity, assessed trials for risk of bias and created summary of findings tables using GRADE.
MAIN RESULTS
The review now includes seven trials with a total of 479 participants. In only one trial, with 95 participants, perazine appeared superior to 'active placebo' (trimipramine) at five weeks for the outcome of 'no important global improvement' (n = 95, RR 0.43 CI 0.2 to 0.8, low quality evidence), but there was no statistically significant difference in most measures of mental state. Perazine did not induce more general adverse events than placebo but more participants received at least one dose of antiparkinson medication (n = 95, RR 4.50 CI 1.0 to 19.5, very low quality evidence).Six small trials comparing perazine with other antipsychotics, including 384 participants in total, were incompletely reported and the outcomes were presented in various ways so that meta-analysis was not possible on most occasions. In the six studies, a similar number of participants receiving perazine or comparator antipsychotics (amisulpride, haloperidol, olanzapine, ziprasidone, zotepine) left the studies early (n = 384, RR 0.97 CI 0.68 to 1.38, low quality evidence). The results on efficacy could not be meta-analysed because the authors presented their results in very different ways. No obvious differences in adverse events between perazine and other antipsychotics could be derived from the limited data. Two haloperidol comparisons did not present extrapyramidal side-effects in a way that was suitable for use in meta-analysis, but three small comparisons with the second-generation antipsychotics zotepine and amisulpride showed no higher risk of akathisia (n = 111, RR 0.31 CI 0.1 to 1.1), dyskinesia (n = 111, RR 0.47 CI 0.1 to 3.5), parkinsonism (n = 81, RR 1.21 CI 0.5 2.8) or tremor (n = 40, RR 0.80 CI 0.3 to 2.6) with perazine.
AUTHORS' CONCLUSIONS
The number, size and reporting of randomised controlled perazine trials are insufficient to present firm conclusions about the properties of this antipsychotic. It is possible that perazine is associated with a similar risk of extrapyramidal side-effects as some atypical antipsychotics but this is based on small comparisons. This should be clarified in larger, well-designed trials.
Topics: Antipsychotic Agents; Humans; Perazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 24425538
DOI: 10.1002/14651858.CD002832.pub3 -
The Cochrane Database of Systematic... Jan 2014Trifluoperazine is a long-established high potency typical antipsychotic drug used in the treatment of schizophrenia and schizophrenia-like illnesses. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Trifluoperazine is a long-established high potency typical antipsychotic drug used in the treatment of schizophrenia and schizophrenia-like illnesses.
OBJECTIVES
To determine absolute effects of trifluoperazine for schizophrenia and schizophrenia-like illnesses compared with placebo.To critically appraise and summarise current evidence on the resource use, cost and economic evaluation of trifluoperazine compared with placebo for schizophrenia.
SEARCH METHODS
Searches of the Cochrane Schizophrenia Group's register of trials (July 2012), supplemented with handsearching, reference searching, personal communication and contact with industry. Two review authors undertook a search for economic studies using the Cochrane Schizophrenia Group's Health Economic Database (CSzGHED) on the 9th April 2013.
SELECTION CRITERIA
All available clinical randomised trials involving people with schizophrenia and schizophrenia-like illnesses that compare trifluoperazine with placebo.
DATA COLLECTION AND ANALYSIS
Studies for the effects of interventions were reliably selected by a review team and data were doubly independently extracted to reduce bias. We only used dichotomous data, using intention-to-treat analysis when possible. Data were estimated using risk ratio (RR) with 95% confidence intervals (CI). A 'Summary of findings' table was produced, where possible, for each primary outcome using GRADE. Economic studies were searched and reliably selected by review authors (VF and SS) to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary.
MAIN RESULTS
This review included 10 studies with a total number of 686 participants featuring in 20 different outcomes of interest. Overall, there was significant clinical improvement in clinical global state at medium term amongst people receiving trifluoperazine (3 RCTs, n = 417, RR 4.61, CI 1.54 to 13.84, low quality evidence) and significantly fewer people receiving trifluoperazine left the studies early due to relapse or worsening at medium term (2 RCTs, n = 381, RR 0.34, CI 0.23 to 0.49, low quality evidence). However, results were equivocal for leaving the study early at medium term for any reason (2 RCTs, n = 391, RR 0.80, CI 0.17 to 3.81, very low quality evidence) and due to severe adverse effects (2 RCTs, n = 391, RR 1.54, CI 0.56 to 4.24, very low quality evidence). Equivocal data were also found for intensified symptoms at medium term (2 RCTs, n = 80, RR 1.05, CI 0.54 to 2.05, very low quality evidence) and rates of agitation or distress again at medium term (1 RCT, n = 52, RR 2.00, CI 0.19 to 20.72, very low quality evidence). Comparison between low and high-dose trifluoperazine with placebo from a single study provided equivocal evidence of effects. For economic outcomes, we valued outcomes in GBP terms and presented them in additional tables; there was an estimated saving of £3488.3 in favour of trifluoperazine. However, numerous assumptions were made and these savings need to be interpreted in light of those assumptions.
AUTHORS' CONCLUSIONS
Our results agree with existing evidence that compared to placebo, trifluoperazine is an effective antipsychotic for people with schizophrenia. Furthermore, our review provides supportive evidence that trifluoperazine increases the risk of extrapyramidal adverse effects. Although the effect sizes against placebo are similar to those observed with other agents, they are based on data from many small, pre-CONSORT trials with generally either a low or very low GRADE evidence that has limited implication for clinical practice. Large, independent trials are needed that adhere to the CONSORT statement to compare trifluoperazine with placebo used in the treatment of schizophrenia and schizophrenia-like illnesses.
Topics: Antipsychotic Agents; Dyskinesia, Drug-Induced; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Trifluoperazine
PubMed: 24414883
DOI: 10.1002/14651858.CD010226.pub2 -
The Cochrane Database of Systematic... Jan 2014Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia.
OBJECTIVES
To review the effects of chlorpromazine compared with placebo, for the treatment of schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (15 May 2012). We also searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care.
DATA COLLECTION AND ANALYSIS
We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. We analysed dichotomous data using risk ratio (RR) and estimated the 95% confidence interval (CI) around this. We excluded continuous data if more than 50% of participants were lost to follow-up. Where continuous data were included, we analysed this data using mean difference (MD) with a 95% confidence interval. We used a fixed-effect model.
MAIN RESULTS
We inspected over 1100 electronic records. The review currently includes 315 excluded studies and 55 included studies. The quality of the evidence is very low. We found chlorpromazine reduced the number of participants experiencing a relapse compared with placebo during six months to two years follow-up (n = 512, 3 RCTs, RR 0.65 CI 0.47 to 0.90), but data were heterogeneous. No difference was found in relapse rates in the short, medium or long term over two years, although data were also heterogeneous. We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n = 1164, 14 RCTs, RR 0.71 CI 0.58 to 0.86). Fewer people allocated to chlorpromazine left trials early ( n = 1831, 27 RCTs, RR 0.64 CI 0.53 to 0.78) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n = 1627, 23 RCTs, RR 2.79 CI 2.25 to 3.45), it increases a person's chances of experiencing acute movement disorders (n = 942, 5 RCTs, RR 3.47 CI 1.50 to 8.03) and parkinsonism (n = 1468, 15 RCTs, RR 2.11 CI 1.59 to 2.80). Akathisia did not occur more often in the chlorpromazine group than placebo. Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n = 1488, 18 RCTs, RR 2.38 CI 1.74 to 3.25) and considerable weight gain (n = 165, 5 RCTs, RR 4.92 CI 2.32 to 10.43).
AUTHORS' CONCLUSIONS
The results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well-established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients.
Topics: Antipsychotic Agents; Chlorpromazine; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Schizophrenia; Secondary Prevention
PubMed: 24395698
DOI: 10.1002/14651858.CD000284.pub3 -
World Journal of Gastroenterology Dec 2013To assess systematically the safety and efficacy of bile leakage test in liver resection. (Meta-Analysis)
Meta-Analysis Review
AIM
To assess systematically the safety and efficacy of bile leakage test in liver resection.
METHODS
Randomized controlled trials and controlled clinical trials involving the bile leakage test were included in a systematic literature search. Two authors independently assessed the studies for inclusion and extracted the data. A meta-analysis was conducted to estimate postoperative bile leakage, intraoperative positive bile leakage, and complications. We used either the fixed-effects or random-effects model.
RESULTS
Eight studies involving a total of 1253 patients were included and they all involved the bile leakage test in liver resection. The bile leakage test group was associated with a significant reduction in bile leakage compared with the non-bile leakage test group (RR = 0.39, 95%CI: 0.23-0.67; I (2) = 3%). The white test had superiority for detection of intraoperative bile leakage compared with the saline solution test (RR = 2.38, 95%CI: 1.24-4.56, P = 0.009). No significant intergroup differences were observed in total number of complications, ileus, liver failure, intraperitoneal hemorrhage, pulmonary disorder, abdominal infection, and wound infection.
CONCLUSION
The bile leakage test reduced postoperative bile leakage and did not increase incidence of complications. Fat emulsion is the best choice of solution for the test.
Topics: Anastomotic Leak; Bile Duct Diseases; Chi-Square Distribution; Diagnostic Techniques, Digestive System; Fat Emulsions, Intravenous; Hepatectomy; Humans; Indocyanine Green; Methylene Blue; Odds Ratio; Predictive Value of Tests
PubMed: 24363535
DOI: 10.3748/wjg.v19.i45.8420 -
Schizophrenia Bulletin Nov 2013Fluphenazine, a phenothiazine derivative, was one of the first drugs to be classed as an "antipsychotic" and was approved by the Food and Drug Administration in 1959. In... (Comparative Study)
Comparative Study Review
Fluphenazine, a phenothiazine derivative, was one of the first drugs to be classed as an "antipsychotic" and was approved by the Food and Drug Administration in 1959. In Britain, it was first used for the relief of anxiety. The American reports, however, were the first to indicate its value in psychotic illness. Fluphenazine is an inexpensive and widely accessible antipsychotic drug that has been available to treat people with schizophrenia for five decades. We updated our original search (from September 2006) using The Cochrane Schizophrenia Group Trials register (May 2012); we found no new relevant studies. Seven randomized controlled trials (RCTs) were included with a total of N = 439 participants. Results, based on this small selection of studies, suggested that there was no significant difference between oral fluphenazine and placebo for most outcomes, including global state and leaving the study early. Results did suggest a statistically significant effect favoring oral fluphenazine in the short term for levels of relapse (n = 38, 1 RCT, RR 0.25 CI 0.06-1.03) with levels of extrapyramidal adverse effects more frequent with oral fluphenazine. The findings in this review confirm much that clinicians and recipients of care already know, but they provide quantification to support clinical impression. In this review, for perhaps the first time, we objectively quantified the effects of oral administration of fluphenazine in comparison with placebo. It is indeed a potent antipsychotic but with considerable adverse effects. Other drugs may well be preferable.
Topics: Antipsychotic Agents; Fluphenazine; Humans; Placebos; Schizophrenia
PubMed: 24072807
DOI: 10.1093/schbul/sbt140 -
The European Respiratory Journal Mar 2014Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for... (Review)
Review
Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for drug-susceptible TB patients. In order to speed up novel treatment for MDR-TB, we suggest considering expanding the indications of already available drugs. Six drugs with antimicrobial activity (phenothiazine, metronidazole, doxycycline, disulfiram, tigecycline and co-trimoxazole) are not listed in the World Health Organization guidelines on MDR-TB treatment but could be potential candidates for evaluation against Mycobacterium tuberculosis. A systematic review was conducted to evaluate antituberculous activity of these drugs against M. tuberculosis. We searched PubMed, Google Scholar and Embase for English articles published up to December 31, 2012. We reviewed in vitro, in vivo and clinical antituberculous activity of these drugs in addition to pharmacokinetics and side-effects. Of the drugs effective against actively replicating M. tuberculosis, co-trimoxazole seems to be the most promising, because of its consistent pharmacokinetic profile, easy penetration into tissue and safety profile. For the dormant state of TB, thioridazine may play a potential role as an adjuvant for treatment of MDR-TB. A strategy consisting of pharmacokinetic/pharmacodynamic studies, dose finding and phase III studies is needed to explore the role of these drugs in MDR-TB treatment.
Topics: Anti-Infective Agents; Antitubercular Agents; Chemistry, Pharmaceutical; Clinical Trials as Topic; Disulfiram; Doxycycline; Drug Design; Humans; Metronidazole; Minocycline; Mycobacterium tuberculosis; Phenothiazines; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant
PubMed: 23988774
DOI: 10.1183/09031936.00113713