-
The Cochrane Database of Systematic... Jun 2017Wendan decoction (WDD) is one of the classical Chinese herb formulas used for psychotic symptoms. It is thought to be safe, accessible and inexpensive. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Wendan decoction (WDD) is one of the classical Chinese herb formulas used for psychotic symptoms. It is thought to be safe, accessible and inexpensive.
OBJECTIVES
To investigate the effects of WDD for treatment of people with schizophrenia or schizophrenia-like illness compared with placebo, antipsychotic drugs and other interventions for outcomes of clinical importance.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (February 2016), which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, China biomedical databases group (SinoMed, CNKI, VIP, Wanfang) and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the register. We also inspected references of identified studies and contacted relevant authors for additional information.
SELECTION CRITERIA
Randomised controlled trials with useable data comparing WDD with antipsychotics, placebo or other interventions for people with schizophrenia.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratios (RR) and 95% confidence intervals (CIs), on an intention-to-treat basis. For continuous data, we estimated mean differences (MD) between groups and their 95% CIs. We employed a random-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included 15 randomised trials (1437 participants) of WDD for schizophrenia. There was a high risk of performance bias within the trials but overall, risk for selection, attrition and reporting bias was low or unclear.Data showed WDD improved the short-term global state of participants compared with placebo or no treatment (1 RCT n = 72, RR 0.53, 95% CI 0.39 to 0.73, low-quality evidence).When WDD was compared with antipsychotic drugs, such as chlorpromazine or risperidone, no difference in short-term global state of participants was observed (2 RCTs n = 140, RR 1.18 95% CI 0.98 to 1.43, moderate-quality evidence) and mental state (total endpoint Positive and Negative Syndrome Scale (PANSS): 2 RCTs, n = 140, MD 0.84, 95% CI -4.17 to 5.84, low-quality evidence). However, WDD was associated with fewer people experiencing extrapyramidal effects (EPS) compared with other treatments (2 RCTs 0/70 versus 47/70, n = 140, RR 0.02, 95% CI 0.00 to 0.15, moderate-quality evidence).WDD is often used as an add-on intervention alongside antipsychotics. When WDD + antipsychotic was compared to antipsychotic alone, the combination group had better global state (short-term results, 6 RCTs, n = 684, RR 0.60, 95% CI 0.50 to 0.72, moderate-quality evidence) and mental state (short-term total endpoint PANSS: 5 RCTs, n = 580, MD -11.64, 95% CI -13.33 to - 9.94, low-quality evidence), fewer people with EPS (2 RCTs n = 308, RR 0.46, 95% CI 0.30 to 0.70, moderate-quality evidence) and reduction of the mean use of risperidone (1 RCT n = 107, MD -0.70, 95% CI -0.87 to -0.53, low-quality evidence). But, there was no effect on weight gain (1 RCT n = 108, RR 0.50, 95% CI 0.20 to 1.24, low-quality evidence).When WDD + low-dose antipsychotic was compared with normal-dose antipsychotic alone, the combination again showed benefits for short-term global state (7 RCTs n = 522, RR 0.69, 95% CI 0.51 to 0.93, moderate-quality evidence), mental state (total endpoint PANSS: 4 RCTs n = 250, MD -9.53, 95% CI -17.82 to -1.24, low-quality evidence), and fewer participants with EPS (3 RCTS n = 280, RR 0.29, 95% CI 0.16 to 0.51, moderate-quality evidence).Across all comparisons, we found no data on outcomes directly reporting quality of life, hospital service use and economics.
AUTHORS' CONCLUSIONS
Limited evidence suggests that WDD may have some positive short-term antipsychotic global effects compared to placebo or no treatment. However when WDD was compared with other antipsychotics there was no effect on global or mental state, but WDD was associated with fewer adverse effects. When WDD was combined with an antipsychotic, positive effects were found for global and mental state and the combination caused fewer adverse effects. The available evidence is not high quality. Better designed large studies are needed to fully and fairly test the effects of WDD for people with schizophrenia.
Topics: Antipsychotic Agents; Chlorpromazine; Drug Therapy, Combination; Drugs, Chinese Herbal; Dyskinesia, Drug-Induced; Humans; Patient Satisfaction; Quality of Life; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia
PubMed: 28657646
DOI: 10.1002/14651858.CD012217.pub2 -
The Cochrane Database of Systematic... Apr 2017The World Health Organization (WHO) Model Lists of Essential Medicines lists chlorpromazine as one of its five medicines used in psychotic disorders. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The World Health Organization (WHO) Model Lists of Essential Medicines lists chlorpromazine as one of its five medicines used in psychotic disorders.
OBJECTIVES
To determine chlorpromazine dose response and dose side-effect relationships for schizophrenia and schizophrenia-like psychoses.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (December 2008; 2 October 2014; 19 December 2016).
SELECTION CRITERIA
All relevant randomised controlled trials (RCTs) comparing low doses of chlorpromazine (≤ 400 mg/day), medium dose (401 mg/day to 800 mg/day) or higher doses (> 800 mg/day) for people with schizophrenia, and which reported clinical outcomes.
DATA COLLECTION AND ANALYSIS
We included studies meeting review criteria and providing useable data. Review authors extracted data independently. For dichotomous data, we calculated fixed-effect risk ratios (RR) and their 95% confidence intervals (CIs). For continuous data, we calculated mean differences (MD) and their 95% CIs based on a fixed-effect model. We assessed risk of bias for included studies and graded trial quality using GRADE (Grading of Recommendations Assessment, Development and Evaluation).
MAIN RESULTS
As a result of searches undertaken in 2014, we found one new study and in 2016 more data for already included studies. Five relevant studies with 1132 participants (585 are relevant to this review) are now included. All are hospital-based trials and, despite over 60 years of chlorpromazine use, have durations of less than six months and all are at least at moderate risk of bias. We found only data on low-dose (≤ 400 mg/day) versus medium-dose chlorpromazine (401 mg/day to 800 mg/day) and low-dose versus high-dose chlorpromazine (> 800 mg/day).When low-dose chlorpromazine (≤ 400 mg/day) was compared to medium-dose chlorpromazine (401 mg/day to 800 mg/day), there was no clear benefit of one dose over the other for both global and mental state outcomes (low-quality and very low-quality evidence). There was also no clear evidence for people in one dosage group being more likely to leave the study early, over the other dosage group (moderate-quality evidence). Similar numbers of participants from each group experienced agitation and restlessness (very low-quality evidence). However, significantly more people in the medium-dose group (401 mg/day to 800 mg/day) experienced extrapyramidal symptoms in the short term (2 RCTS, n = 108, RR 0.47, 95% CI 0.30 to 0.74, moderate-quality evidence). No data for death were available.When low-dose chlorpromazine (≤ 400 mg/day) was compared to high-dose chlorpromazine (> 800 mg/day), data from one study with 416 patients were available. Clear evidence of a benefit of the high dose was found with regards to global state. The low-dose group had significantly fewer people improving (RR 1.13, 95% CI 1.01 to 1.25, moderate-quality evidence). There was also a marked difference between the number of people leaving the study from each group for any reason, with significantly more people leaving from the high-dose group (RR 0.60, 95% CI 0.40 to 0.89, moderate-quality evidence). More people in the low-dose group had to leave the study due to deterioration in behaviour (RR 2.70, 95% CI 1.34 to 5.44, low-quality evidence). There was clear evidence of a greater risk of people experiencing extrapyramidal symptoms in general in the high-dose group (RR 0.43, 95% CI 0.32 to 0.59, moderate-quality evidence). One death was reported in the high-dose group yet no effect was shown between the two dosage groups (RR 0.33, 95% CI 0.01 to 8.14, moderate-quality evidence). No data for mental state were available.
AUTHORS' CONCLUSIONS
The dosage of chlorpromazine has changed drastically over the past 50 years with lower doses now being the preferred of choice. However, this change was gradual and arose not due to trial-based evidence, but due to clinical experience and consensus. Chlorpromazine is one of the most widely used antipsychotic drugs yet appropriate use of lower levels has come about after many years of trial and error with much higher doses. In the absence of high-grade evaluative studies, clinicians have had no alternative but to learn from experience. However, such an approach can lack scientific rigor and does not allow for proper dissemination of information that would assist clinicians find the optimum treatment dosage for their patients. In the future, data for recently released medication should be available from high-quality trials and studies to provide optimum treatment to patients in the shortest amount of time.
Topics: Antipsychotic Agents; Barbiturates; Chloral Hydrate; Chlorpromazine; Drug Administration Schedule; Humans; Hypnotics and Sedatives; Patient Dropouts; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 28407198
DOI: 10.1002/14651858.CD007778.pub2 -
The Cochrane Database of Systematic... Apr 2017Schizophrenia is a chronic, disabling and severe mental disorder, characterised by disturbance in perception, thought, language, affect and motor behaviour.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Schizophrenia is a chronic, disabling and severe mental disorder, characterised by disturbance in perception, thought, language, affect and motor behaviour. Chlorpromazine and clotiapine are among antipsychotic drugs used for the treatment of people with schizophrenia.
OBJECTIVES
To determine the clinical effects, safety and cost-effectiveness of chlorpromazine compared with clotiapine for adults with schizophrenia.
SEARCH METHODS
We searched Cochrane Schizophrenia's Trials Register (last update search 16/01/2016), which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the Register.
SELECTION CRITERIA
All randomised clinical trials focusing on chlorpromazine versus clotiapine for schizophrenia. We included trials meeting our selection criteria and reporting useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
We have included four studies, published between 1974 and 2003, randomising 276 people with schizophrenia to receive either chlorpromazine or clotiapine. The studies were poor at concealing allocation of treatment and blinding of outcome assessment. Our main outcomes of interest were clinically important change in global and mental state, specific change in negative symptoms, incidence of movement disorder (dyskinesia), leaving the study early for any reason, and costs. All reported data were short-term (under six months' follow-up).The trials did not report data for the important outcomes of clinically important change in global or mental state, or cost of care. Improvement in mental state was reported using the Positive and Negative Syndrome Scale (PANSS). When chlorpromazine was compared with clotiapine the average improvement scores for mental state using the PANSS total was higher in the clotiapine group (1 RCT, N = 31, MD 11.50 95% CI 9.42 to 13.58, very low-quality evidence). The average change scores on the PANSS negative sub-scale were similar between treatment groups (1 RCT, N = 21, MD -0.97 95% CI -2.76 to 0.82, very low-quality evidence). There was no clear difference in incidence of dyskinesia (1 RCT, N = 68, RR 3.00 95% CI 0.13 to 71.15, very low-quality evidence). Similar numbers of participants left the study early from each treatment group (3 RCTs, N = 158, RR 0.68 95% CI 0.24 to 1.88, very low-quality evidence).
AUTHORS' CONCLUSIONS
Clinically important changes in global and mental state were not reported. Only one trial reported the average change in overall mental state; results favour clotiapine but these limited data are very difficult to trust due to methodological limitations of the study. The comparative effectiveness of chlorpromazine compared to clotiapine on change in global state remains unanswered. Results in this review suggest chlorpromazine and clotiapine cause similar adverse effects, although again, the quality of evidence for this is poor, making firm conclusions difficult.
Topics: Antipsychotic Agents; Chlorpromazine; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Intention to Treat Analysis; Patient Dropouts; Randomized Controlled Trials as Topic; Risk; Schizophrenia
PubMed: 28387925
DOI: 10.1002/14651858.CD011810.pub2 -
The Cochrane Database of Systematic... Mar 2017Chlorpromazine, a widely available and inexpensive antipsychotic drug, is considered the benchmark treatment for schizophrenia worldwide. Metiapine, a dibenzothiazepine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chlorpromazine, a widely available and inexpensive antipsychotic drug, is considered the benchmark treatment for schizophrenia worldwide. Metiapine, a dibenzothiazepine derivative, has been reported to have potent antipsychotic characteristics. However, no evidence currently exists on the effectiveness of chlorpromazine in treatment of people with schizophrenia compared to metiapine, a newer antipsychotic.
OBJECTIVES
To compare the effect of chlorpromazine versus metiapine for the treatment of people with schizophrenia SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials in November 2015 and 2016.
SELECTION CRITERIA
All randomised controlled trials (RCTs) focusing on chlorpromazine versus metiapine for adults with schizophrenia. We included trials meeting our selection criteria and reporting useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included three studies randomising 161 people with schizophrenia. Data were available for only two of our seven prestated main outcomes. Clinically important improvement in global state was measured using the Clinical Global Impression (CGI). There was no clear difference between chlorpromazine and metiapine groups (2 RCTs, n = 120, RR 1.11, 95% CI 0.84 to 1.47, very low quality evidence) and numbers of participants with parkinsonism at eight weeks were similar (2 RCTs, n = 70, RR 0.97, 95% CI 0.46 to 2.03, very low quality evidence). There were no useable data available for the other key outcomes of clinically important improvement in mental state, readmission due to relapse, satisfaction with treatment, aggressive or violent behaviour, or cost of care.
AUTHORS' CONCLUSIONS
Chlorpromazine has been the mainstay treatment for schizophrenia for decades, yet available evidence comparing this drug to metiapine fails to provide high-quality trial based data. However, the need to determine whether metiapine is more or less effective than chlorpromazine seems to be lacking in clinical relevance and future research on this comparison seems unlikely.
Topics: Adult; Antipsychotic Agents; Chlorpromazine; Dibenzothiazepines; Humans; Parkinson Disease, Secondary; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 28349512
DOI: 10.1002/14651858.CD011655.pub2 -
The Cochrane Database of Systematic... Nov 2016Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such situations should ensure that the person becomes calm swiftly and safely.
OBJECTIVES
To examine whether haloperidol plus promethazine is an effective treatment for psychosis-induced aggression.
SEARCH METHODS
On 6 May 2015 we searched the Cochrane Schizophrenia Group's Register of Trials, which is compiled by systematic searches of major resources (including MEDLINE, EMBASE, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings.
SELECTION CRITERIA
All randomised clinical trials with useable data focusing on haloperidol plus promethazine for psychosis-induced aggression.
DATA COLLECTION AND ANALYSIS
We independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We found two new randomised controlled trials (RCTs) from the 2015 update searching. The review now includes six studies, randomising 1367 participants and presenting data relevant to six comparisons.When haloperidol plus promethazine was compared with haloperidol alone for psychosis-induced aggression for the outcome not tranquil or asleep at 30 minutes, the combination treatment was clearly more effective (n=316, 1 RCT, RR 0.65, 95% CI 0.49 to 0.87, high-quality evidence). There were 10 occurrences of acute dystonia in the haloperidol alone arm and none in the combination group. The trial was stopped early as haloperidol alone was considered to be too toxic.When haloperidol plus promethazine was compared with olanzapine, high-quality data showed both approaches to be tranquillising. It was suggested that the combination of haloperidol plus promethazine was more effective, but the difference between the two approaches did not reach conventional levels of statistical significance (n=300, 1 RCT, RR 0.60, 95% CI 0.22 to 1.61, high-quality evidence). Lower-quality data suggested that the risk of unwanted excessive sedation was less with the combination approach (n=116, 2 RCTs, RR 0.67, 95% CI 0.12 to 3.84).When haloperidol plus promethazine was compared with ziprasidone all data were of lesser quality. We identified no binary data for the outcome tranquil or asleep. The average sedation score (Ramsay Sedation Scale) was lower for the combination approach but not to conventional levels of statistical significance (n=60, 1 RCT, MD -0.1, 95% CI - 0.58 to 0.38). These data were of low quality and it is unclear what they mean in clinical terms. The haloperidol plus promethazine combination appeared to cause less excessive sedation but again the difference did not reach conventional levels of statistical significance (n=111, 2 RCTs, RR 0.30, 95% CI 0.06 to 1.43).We found few data for the comparison of haloperidol plus promethazine versus haloperidol plus midazolam. Average Ramsay Sedation Scale scores suggest the combination of haloperidol plus midazolam to be the most sedating (n=60, 1 RCT, MD - 0.6, 95% CI -1.13 to -0.07, low-quality evidence). The risk of excessive sedation was considerably less with haloperidol plus promethazine (n=117, 2 RCTs, RR 0.12, 95% CI 0.03 to 0.49, low-quality evidence). Haloperidol plus promethazine seemed to decrease the risk of needing restraints by around 12 hours (n=60, 1 RCT, RR 0.24, 95% CI 0.10 to 0.55, low-quality evidence). It may be that use of midazolam with haloperidol sedates swiftly, but this effect does not last long.When haloperidol plus promethazine was compared with lorazepam, haloperidol plus promethazine seemed to more effectively cause sedation or tranquillisation by 30 minutes (n=200, 1 RCT, RR 0.26, 95% CI 0.10 to 0.68, high-quality evidence). The secondary outcome of needing restraints or seclusion by 12 hours was not clearly different between groups, with about 10% in each group needing this intrusive intervention (moderate-quality evidence). Sedation data were not reported, however, the combination group did have less 'any serious adverse event' in 24-hour follow-up, but there were not clear differences between the groups and we are unsure exactly what the adverse effect was. There were no deaths.When haloperidol plus promethazine was compared with midazolam, there was clear evidence that midazolam is more swiftly tranquillising of an aggressive situation than haloperidol plus promethazine (n=301, 1 RCT, RR 2.90, 95% CI 1.75 to 4.8, high-quality evidence). On its own, midazolam seems to be swift and effective in tranquillising people who are aggressive due to psychosis. There was no difference in risk of serious adverse event overall (n=301, 1 RCT, RR 1.01, 95% CI 0.06 to 15.95, high-quality evidence). However, 1 in 150 participants allocated haloperidol plus promethazine had a swiftly reversed seizure, and 1 in 151 given midazolam had swiftly reversed respiratory arrest.
AUTHORS' CONCLUSIONS
Haloperidol plus promethazine is effective and safe, and its use is based on good evidence. Benzodiazepines work, with midazolam being particularly swift, but both midazolam and lorazepam cause respiratory depression. Olanzapine intramuscular and ziprasidone intramuscular do seem to be viable options and their action is swift, but resumption of aggression with subsequent need to re-inject was more likely than with haloperidol plus promethazine. Haloperidol used on its own without something to offset its frequent and serious adverse effects does seem difficult to justify.
Topics: Aggression; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Midazolam; Promethazine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic; Restraint, Physical
PubMed: 27885664
DOI: 10.1002/14651858.CD005146.pub3 -
The Cochrane Database of Systematic... Jul 2016Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years.
OBJECTIVES
To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia.
SEARCH METHODS
We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics.
DATA COLLECTION AND ANALYSIS
Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence.
MAIN RESULTS
Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness.
AUTHORS' CONCLUSIONS
Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.
Topics: Administration, Oral; Amisulpride; Antipsychotic Agents; Benzodiazepines; Fluphenazine; Humans; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride; Treatment Outcome
PubMed: 27370402
DOI: 10.1002/14651858.CD010832.pub2 -
The Cochrane Database of Systematic... May 2016Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for hospitalization during pregnancy. While a previous Cochrane review examined interventions for nausea and vomiting in pregnancy, there has not yet been a review examining the interventions for the more severe condition of hyperemesis gravidarum.
OBJECTIVES
To assess the effectiveness and safety, of all interventions for hyperemesis gravidarum in pregnancy up to 20 weeks' gestation.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (20 December 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomized controlled trials of any intervention for hyperemesis gravidarum. Quasi-randomized trials and trials using a cross-over design were not eligible for inclusion.We excluded trials on nausea and vomiting of pregnancy that were not specifically studying the more severe condition of hyperemesis gravidarum.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the eligibility of trials, extracted data and evaluated the risk of bias. Data were checked for accuracy.
MAIN RESULTS
Twenty-five trials (involving 2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. The comparisons covered a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various pharmaceutical interventions. The methodological quality of included studies was mixed. For selected important comparisons and outcomes, we graded the quality of the evidence and created 'Summary of findings' tables. For most outcomes the evidence was graded as low or very low quality mainly due to the imprecision of effect estimates. Comparisons included in the 'Summary of findings' tables are described below, the remaining comparisons are described in detail in the main text.No primary outcome data were available when acupuncture was compared with placebo, There was no clear evidence of differences between groups for anxiodepressive symptoms (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.40; one study, 36 women, very low-quality evidence), spontaneous abortion (RR 0.48, 95% CI 0.05 to 5.03; one study, 57 women, low-quality evidence), preterm birth (RR 0.12, 95% CI 0.01 to 2.26; one study, 36 women, low-quality evidence), or perinatal death (RR 0.57, 95% CI 0.04 to 8.30; one study, 36 women, low-quality evidence).There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (RR 1.40, 95% CI 0.79 to 2.49 and RR 1.51, 95% CI 0.92 to 2.48, respectively; very low-quality evidence).In a study with 92 participants, women taking vitamin B6 had a slightly longer hospital stay compared with placebo (mean difference (MD) 0.80 days, 95% CI 0.08 to 1.52, moderate-quality evidence). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40 to 1.40, low-quality evidence) or side effects.A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15 to 3.55, and MD -0.10, 95% CI -1.63 to 1.43; one study, 83 women, respectively, very low-quality evidence). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23 to 4.69, and RR 2.38, 95% CI 1.10 to 5.11, respectively; moderate-quality evidence). There were no clear differences between groups for other side effects.In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (RR 0.70, 95% CI 0.56 to 0.87, RR 0.48, 95% CI 0.34 to 0.69, and RR 0.31, 95% CI 0.11 to 0.90, respectively, moderate-quality evidence). There were no clear differences between groups for other important outcomes including quality of life and other side effects.In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (MD 0.00, 95% CI -1.39 to 1.39, very low-quality evidence), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00 to 0.94, low-quality evidence) .Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70 to 0.10; very low-quality evidence), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50 to 0.94; four studies, 269 women). For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, there was insufficient evidence to identify differences between groups (very low-quality evidence for all outcomes). In other single studies there were no clear differences between groups for preterm birth or side effects (very low-quality evidence).For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00 to 1.28;one study, 40 women).In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 hours (RR 2.00, 95% CI 1.08 to 3.72; low-quality evidence), but not at 17 days (RR 0.81, 95% CI 0.58 to 1.15, very low-quality evidence). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth.
AUTHORS' CONCLUSIONS
On the basis of this review, there is little high-quality and consistent evidence supporting any one intervention, which should be taken into account when making management decisions. There was also very limited reporting on the economic impact of hyperemesis gravidarum and the impact that interventions may have.The limitations in interpreting the results of the included studies highlights the importance of consistency in the definition of hyperemesis gravidarum, the use of validated outcome measures, and the need for larger placebo-controlled trials.
Topics: Acupuncture Therapy; Adrenal Cortex Hormones; Antiemetics; Female; Humans; Hydrocortisone; Hyperemesis Gravidarum; Metoclopramide; Ondansetron; Placebo Effect; Prednisolone; Pregnancy; Promethazine; Pyridoxine
PubMed: 27168518
DOI: 10.1002/14651858.CD010607.pub2 -
The Cochrane Database of Systematic... Apr 2016In the 1940s reserpine, refined from a plant extract that had been used for centuries, began to be used as a treatment for people with mental disorders and was one of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the 1940s reserpine, refined from a plant extract that had been used for centuries, began to be used as a treatment for people with mental disorders and was one of the very first antipsychotic drugs. Its irreversible pharmacological potency and adverse effects meant that it has been withdrawn in the UK and its role has been superceded by 'newer' compounds. The effects of reserpine are of historical interest although there are some reports of it still being used in highly specialist situations in psychiatry. Chlorpromazine is also an old drug but it is still used for treatment of people with schizophrenia.
OBJECTIVES
To investigate the effects of two old medications (reserpine and chlorpromazine) for people with schizophrenia. Reserpine is now rarely used while chlorpromazine remains on the essential list of drugs of the World Health Organization (WHO).
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (24 March 2016).
SELECTION CRITERIA
We included randomised clinical trials focusing on chlorpromazine versus reserpine for schizophrenia that presented useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The review currently includes nine studies with an average 60 participants per study. All of these studies are now over 60 years old, conducted between 1955 and 1962. When chlorpromazine was compared with reserpine for people with schizophrenia, improvement in global state was better at short term for those receiving chlorpromazine (n = 781, 6 RCTs, RR 'not improved' 0.75 95% CI 0.62 to 0.92, low-quality evidence). Short-term improvement in paranoid distortion was measured using the Multidimensional Scale for Rating Psychiatric Patients (MSRPP). Data showed no clear difference between treatment groups (n = 19, 1 RCT, RR 1.33 95% CI 0.62 to 2.89, very low-quality evidence). There was no difference in functioning: occupational adjustment, medium term (n = 40, 1 RCT, RR 0.83 95% CI 0.47 to 1.47, moderate-quality evidence) and general behaviour (n = 98, 1 RCT, RR 0.79 CI 0.41 to 1.53, moderate-quality evidence). Adverse events were poorly reported. For 'toxic reaction' there was, again, no obvious difference between the two compounds (n = 210, 3 RCTs, RR 1.68 95% CI 0.43 to 6.54, moderate-quality evidence), and this also applied to leaving the study early (n = 229, 4 RCTs, RR 1.16 95% CI 0.94 to 1.42, moderate-quality evidence).
AUTHORS' CONCLUSIONS
Judged by standards of today, the evidence is largely of limited quality. However, some of these 1950s studies are remarkable in their foresight and clarity. Reserpine did have some effect on global state - but chlorpromazine did seem to perform better. Important issues regarding adverse effects were not really addressed by these trials. Chlorpromazine remains on the WHO list of essential drugs. Reserpine is now almost obsolete, although, probably as a result of evidence other than that reported in the pioneering trials used in this review.
Topics: Antipsychotic Agents; Chlorpromazine; Humans; Randomized Controlled Trials as Topic; Reserpine; Schizophrenia
PubMed: 27124109
DOI: 10.1002/14651858.CD012122.pub2 -
The Cochrane Database of Systematic... Apr 2016Chlorpromazine is an aliphatic phenothiazine, which is one of the widely-used typical antipsychotic drugs. Chlorpromazine is reliable for its efficacy and one of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chlorpromazine is an aliphatic phenothiazine, which is one of the widely-used typical antipsychotic drugs. Chlorpromazine is reliable for its efficacy and one of the most tested first generation antipsychotic drugs. It has been used as a 'gold standard' to compare the efficacy of older and newer antipsychotic drugs. Expensive new generation drugs are heavily marketed worldwide as a better treatment for schizophrenia, but this may not be the case and an unnecessary drain on very limited resources.
OBJECTIVES
To compare the effects of chlorpromazine with atypical or second generation antipsychotic drugs, for the treatment of people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register up to 23 September 2013.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared chlorpromazine with any other atypical antipsychotic drugs for treating people with schizophrenia. Adults (as defined in each trial) diagnosed with schizophrenia, including schizophreniform, schizoaffective and delusional disorders were included in this review.
DATA COLLECTION AND ANALYSIS
At least two review authors independently screened the articles identified in the literature search against the inclusion criteria and extracted data from included trials. For homogeneous dichotomous data, we calculated the risk ratio (RR) and the 95% confidence intervals (CIs). For continuous data, we determined the mean difference (MD) values and 95% CIs. We assessed the risk of bias in included studies and rated the quality of the evidence using the GRADE approach.
MAIN RESULTS
This review includes 71 studies comparing chlorpromazine to olanzapine, risperidone or quetiapine. None of the included trials reported any data on economic costs. 1. Chlorpromazine versus olanzapineIn the short term, there appeared to be a significantly greater clinical response (as defined in each study) in people receiving olanzapine (3 RCTs, N = 204; RR 2.34, 95% CI 1.37 to 3.99, low quality evidence). There was no difference between drugs for relapse (1 RCT, N = 70; RR 1.5, 95% CI 0.46 to 4.86, very low quality evidence), nor in average endpoint score using the Brief Psychiatric Rating Scale (BPRS) for mental state (4 RCTs, N = 245; MD 3.21, 95% CI -0.62 to 7.05,very low quality evidence). There were significantly more extrapyramidal symptoms experienced amongst people receiving chlorpromazine (2 RCTs, N = 298; RR 34.47, 95% CI 4.79 to 248.30,very low quality evidence). Quality of life ratings using the general quality of life interview (GQOLI) - physical health subscale were more favourable with people receiving olanzapine (1 RCT, N = 61; MD -10.10, 95% CI -13.93 to -6.27, very low quality evidence). There was no difference between groups for people leaving the studies early (3 RCTs, N = 139; RR 1.69, 95% CI 0.45 to 6.40, very low quality evidence). 2. Chlorpromazine versus risperidoneIn the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or risperidone (7 RCTs, N = 475; RR 0.84, 95% CI 0.53 to 1.34, low quality of evidence), nor in average endpoint score using the BPRS for mental state 4 RCTs, N = 247; MD 0.90, 95% CI -3.49 to 5.28, very low quality evidence), or any observed extrapyramidal adverse effects (3 RCTs, N = 235; RR 1.7, 95% CI 0.85 to 3.40,very low quality evidence). Quality of life ratings using the QOL scale were significantly more favourable with people receiving risperidone (1 RCT, N = 100; MD -14.2, 95% CI -20.50 to -7.90, very low quality evidence). There was no difference between groups for people leaving the studies early (one RCT, N = 41; RR 0.21, 95% CI 0.01 to 4.11, very low quality evidence). 3. Chlorpromazine versus quetiapineIn the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or quetiapine (28 RCTs, N = 3241; RR 0.93, 95% CI 0.81 to 1.06, moderate quality evidence) nor in average endpoint score using the BPRS for mental state (6 RCTs, N = 548; MD -0.18, 95% CI -1.23 to 0.88, very low quality evidence). Quality of life ratings using the GQOL1-74 scale were significantly more favourable with people receiving quetiapine (1 RCT, N = 59; MD -6.49, 95% CI -11.30 to -1.68, very low quality evidence). Significantly more people receiving chlorpromazine experienced extrapyramidal adverse effects (8 RCTs, N = 644; RR 8.03, 95% CI 4.78 to 13.51, low quality of evidence). There was no difference between groups for people leaving the studies early in the short term (12 RCTs, N = 1223; RR 1.04, 95% CI 0.77 to 1.41,moderate quality evidence).
AUTHORS' CONCLUSIONS
Most included trials included inpatients from hospitals in China. Therefore the results of this Cochrane review are more applicable to the Chinese population. Mostincluded trials were short term studies, therefore we cannot comment on the medium and long term use of chlorpromazine compared to atypical antipsychotics. Low qualityy evidence suggests chlorpromazine causes more extrapyramidal adverse effects. However, all studiesused varying dose ranges, and higher doses would be expected to be associated with more adverse events.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Humans; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia
PubMed: 27045703
DOI: 10.1002/14651858.CD010631.pub2 -
Medicina Oral, Patologia Oral Y Cirugia... May 2016Gold standard for the diagnosis of oral dysplasia (OD) and oral squamous cell carcinoma (OSCC) and malignant lesions is the histological examination. Several adjunctive... (Review)
Review
BACKGROUND
Gold standard for the diagnosis of oral dysplasia (OD) and oral squamous cell carcinoma (OSCC) and malignant lesions is the histological examination. Several adjunctive diagnostic techniques have been proposed in order to increase the sensitivity (SE) and specificity (SP) of conventional oral examination and to improve the diagnostic first level accuracy. The aim of this study is to perform a systematic review on non-invasive tools for diagnosis of OD and early OSCC.
MATERIAL AND METHODS
Medline, Scopus, Web of Knowledge databases were searched, using as entry terms "oral dysplasia AND diagnosis" / "oral cancer AND diagnosis". Data extracted from each study included number of lesions evaluated, histopathological diagnosis, SE, SP, positive and negative predictive values (PPV and NPV), diagnostic accuracy (DA) and the main conclusions.
RESULTS
After title and abstract scanning of 11.080 records, we selected 35 articles for full text evaluation. Most evaluated tools were autofluorescence (AF), chemiluminescence (CL), toluidine blu (TL) and chemiluminescence associated with toluidine blue (CLTB).
CONCLUSIONS
There is a great inhomogeneity of the reported values and there is no significant evidence of superiority of one tool over the other. Further clinical trials with a higher level of evidence are necessary in order to assess the real usefulness visual diagnostic tools.
Topics: Carcinoma, Squamous Cell; Humans; Hyperplasia; Mouth Neoplasms; Sensitivity and Specificity; Tolonium Chloride
PubMed: 26946204
DOI: 10.4317/medoral.20996