-
Current Drug Targets 2020Different clinical studies have given inconsistent results on whether the use of antipsychotics increases the risk of thromboembolism. In this paper, we reviewed all... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Different clinical studies have given inconsistent results on whether the use of antipsychotics increases the risk of thromboembolism. In this paper, we reviewed all relevant literature to provide suggestions for clinical diagnosis and treatment.
METHODS
PubMed, Web of Science, EMBASE, MEDLINE, Cochrane and Scopus databases were thoroughly searched up to June 2019. Two researchers independently searched the literature, extracted data. Data were analyzed by Stata 12.0 software.
RESULTS
A total of 22 studies involving 31514226 subjects were included. This meta-analysis showed that patients taking the first- or second-generation antipsychotics had a higher risk of venous thromboembolism and pulmonary embolism than those who did not, and low potency first-generation agents increased the risk of venous thromboembolism more than high potency antipsychotics, and olanzapine, clozapine, haloperidol, perphenazine and risperidone also significantly increased the risk of it. The risk of venous thrombosis in obese people was higher than that in overweight people, patients not less than 65 years old had an increased risk compared with younger patients. In addition, women taking antipsychotics had a higher risk of pulmonary embolism than men.
CONCLUSION
The use of antipsychotics will increase the risk of venous thromboembolism and pulmonary embolism, which will be affected by the type of antipsychotics and patient characteristics.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Data Interpretation, Statistical; Humans; Middle Aged; Observational Studies as Topic; Pulmonary Embolism; Risk Assessment; Risk Factors; Software; Venous Thromboembolism; Young Adult
PubMed: 32321400
DOI: 10.2174/1389450121666200422084414 -
The Cochrane Database of Systematic... Jan 2005Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European countries and Japan.
OBJECTIVES
To examine the clinical effects and safety of perphenazine for those with schizophrenia and schizophrenia-like psychoses.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's register (June 2001), references of all included studies and contacted pharmaceutical companies and authors of included studies in order to identify further trials.
SELECTION CRITERIA
We included all randomised controlled trials that compared perphenazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. We excluded trials of depot formulations of perphenazine.
DATA COLLECTION AND ANALYSIS
Two reviewers independently inspected citations and, where possible, abstracts. We ordered papers, inspected and quality assessed them. We extracted data, again working independently. If loss to follow up was greater than 50% we considered results as 'prone to bias'. For dichotomous data we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD).
MAIN RESULTS
The review currently includes 25 studies with 2478 patients, 2285 of whom had been randomised to interventions that were relevant for the review such as perphenazine, other antipsychotic drugs or placebo. The trials were carried out between 1961 and 1993. All but one trial were short term with a duration of between ten days and 12 weeks. Descriptions of allocation and blinding were usually incomplete. Six studies (n=300) compared perphenazine with placebo. Perphenazine was associated with fewer participants leaving the trials early due to relapse or worsening of symptoms (n=84, RR 0.1 CI 0.03 - 0.4, NNT 2 CI 1 to 20). Twenty studies compared perphenazine (n=738) with other antipsychotics (n=1278). Perphenazine seemed as effective as other antipsychotics ('global state unimproved or worse' n=1327, RR 1.0 CI 0.9 to 1.2). We found no clear differences in terms of specific aspects of efficacy, behaviour or tolerability. However, interpretation of findings of the review was limited by poor reporting and the use of 24 different comparator antipsychotics in the 20 trials.
AUTHORS' CONCLUSIONS
Although perphenazine has been randomised for more than 40 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. At best we can say that perphenazine showed similar effects and adverse events as several of the other pooled antipsychotic drugs. Since perphenazine is a relatively inexpensive and frequently used compound, further trials are justified to clarify the properties of this classical antipsychotic drug.
Topics: Antipsychotic Agents; Humans; Mental Disorders; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 15674907
DOI: 10.1002/14651858.CD003443.pub2 -
The Cochrane Database of Systematic... Apr 2005Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece, Italy, the Netherlands and the UK. Benperidol is a butyrophenone antipsychotic, with the highest neuroleptic potency in terms of D2 receptor blockade. Those taking it are therefore reputed to be at high risk of extrapyramidal side effects, but benperidol's unusual profile may render it valuable to subgroups of people with schizophrenia.
OBJECTIVES
To examine the clinical effects and safety of benperidol for those with schizophrenia and schizophrenia-like psychoses.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's register (November 2004) for this update.
SELECTION CRITERIA
We included all randomised controlled trials that compared benperidol with other treatments for people with schizophrenia, or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We reliably selected studies, quality rated them and extracted data. We independently extracted data but excluded data if loss to follow up was greater than 50%. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis.
MAIN RESULTS
The update yielded no further studies for inclusion in the review. We identified only one unpublished poorly randomised controlled trial (N=40, duration 30 days, comparison perphenazine). Although benperidol was inferior to perphenazine (1 RCT, N=40, global state no better or worse RR 8.0 CI 2.1 to 30, NNH 1.4 CI 1 to 2) poor reporting suggests that an overestimate of effect is likely. It was not possible to report other outcomes.
AUTHORS' CONCLUSIONS
Currently, there are insufficient data from randomised trials to assess the clinical effects of benperidol. This compound merits further research interest.
Topics: Antipsychotic Agents; Benperidol; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 15846648
DOI: 10.1002/14651858.CD003083.pub2 -
The Cochrane Database of Systematic... May 2014Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to promote additional response. The antiepileptic carbamazepine is one such drug.
OBJECTIVES
To examine whether carbamazepine or oxcarbazepine alone is an effective treatment for schizophrenia and schizoaffective psychoses and whether carbamazepine or oxcarbazepine augmentation of neuroleptic medication is an effective treatment for the same illnesses.
SEARCH METHODS
For the original version we searched The Cochrane Schizophrenia Group's Register of Trials (December 2001), The Cochrane Library (Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1980-2001), Biological Abstracts (1980-2001), PsycLIT (1886-2001) and PSYNDEX (1974-2001). For the most recent update we searched the Cochrane Schizophrenia Group's Register of Trials in July 2012. We also inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors for additional data.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing carbamazepine or compounds of the carbamazepine family with placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For homogenous dichotomous data we calculated fixed-effect, risk ratio (RR), with 95% confidence intervals (CIs) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). We assessed the risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The updated search did not reveal any further studies that met our inclusion criteria. The number of included studies therefore remains at 10 with the number of participants randomised still 283.One study comparing carbamazepine with placebo as the sole treatment for schizophrenia was abandoned early due to high relapse rate with 26 out of 31 participants relapsing by three months. No effect of carbamazepine was evident with no difference in relapse between the two groups (1 RCT n = 31, RR 1.07 CI 0.78 to 1.45). Another study compared carbamazepine with antipsychotics as the sole treatment for schizophrenia. No differences in terms of mental state were found when comparing 50% reduction in Brief Psychiatric Rating Scale (BPRS) scores (1 RCT n = 38, RR 1.23 CI 0.78 to 1.92). A favourable effect for carbamazepine was found when more people who received the antipsychotic (perphenazine) had parkinsonism (1 RCT n = 38, RR 0.03 CI 0.00 to 0.043). Eight studies compared adjunctive carbamazepine versus adjunctive placebo, we were able use GRADE for quality of evidence for these results. Adding carbamazepine to antipsychotic treatment was as acceptable as adding placebo with no difference between the numbers leaving the study early from each group (8 RCTs n = 182, RR 0.47 CI 0.16 to 1.35, very low quality evidence). Carbamazepine augmentation was superior compared with antipsychotics alone in terms of overall global improvement, but participant numbers were low (2 RCTs n = 38, RR 0.57 CI 0.37 to 0.88). There were no differences for the mental state outcome of 50% reduction in BPRS scores (6 RCTs n = 147, RR 0.86 CI 0.67 to 1.12, low quality evidence). Less people in the carbamazepine augmentation group had movement disorders than those taking haloperidol alone (1 RCT n = 20, RR 0.38 CI 0.14 to 1.02). No data were available for the effects of carbamazepine on subgroups of people with schizophrenia and aggressive behaviour, negative symptoms or EEG abnormalities or with schizoaffective disorder.
AUTHORS' CONCLUSIONS
Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommended for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. At present large, simple well-designed and reported trials are justified - especially if focusing on people with violent episodes and people with schizoaffective disorders or those with both schizophrenia and EEG abnormalities.
Topics: Antimanic Agents; Antipsychotic Agents; Carbamazepine; Combined Modality Therapy; Humans; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia
PubMed: 24789267
DOI: 10.1002/14651858.CD001258.pub3 -
The Cochrane Database of Systematic... Nov 2017Oral zuclopenthixol dihydrochloride (Clopixol) is an anti-psychotic treatment for people with psychotic symptoms, especially those with schizophrenia. It is associated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral zuclopenthixol dihydrochloride (Clopixol) is an anti-psychotic treatment for people with psychotic symptoms, especially those with schizophrenia. It is associated with neuroleptic malignant syndrome, a prolongation of the QTc interval, extra-pyramidal reactions, venous thromboembolism and may modify insulin and glucose responses.
OBJECTIVES
To determine the effects of zuclopenthixol dihydrochloride for treatment of schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (latest search 09 June 2015). There were no language, date, document type, or publication status limitations for inclusion of records in the register.
SELECTION CRITERIA
All randomised controlled trials (RCTs) focusing on zuclopenthixol dihydrochloride for schizophrenia. We included trials meeting our inclusion 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-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included 20 trials, randomising 1850 participants. Data were reported for 12 comparisons, predominantly for the short term (up to 12 weeks) and inpatient populations. Overall risk of bias for included studies was low to unclear.Data were unavailable for many of our pre-stated outcomes of interest. No data were available, across all comparisons, for death, duration of stay in hospital and general functioning.Zuclopenthixol dihydrochloride versus: 1. placeboMovement disorders (EPSEs) were similar between groups (1 RCT, n = 28, RR 6.07 95% CI 0.86 to 43.04 very low-quality evidence). There was no clear difference in numbers leaving the study early (2 RCTs, n = 100, RR 0.29, 95% CI 0.01 to 6.60, very low-quality evidence). 2. chlorpromazineNo clear differences were found for the outcomes of global state (average CGI-SI endpoint score) (1 RCT, n = 60, MD 0.00, 95% CI -0.49 to 0.49) or movement disorders (EPSEs) (3 RCTs, n = 199, RR 0.94, 95% CI 0.61 to 1.45), both very low-quality evidence. More people left the study early for any reason from the zuclopenthixol group (6 RCTs, n = 766, RR 0.54, 95% CI 0.36 to 0.81, low-quality evidence). 3. chlorprothixeneThere was no clear difference in numbers leaving the study early for any reason (1 RCT, n = 20, RR 1.00, 95% CI 0.34 to 2.93, very low-quality evidence). 4. clozapineNo useable data were presented. 5. haloperidolNo clear differences between treatment groups were found for the outcomes global state score (average CGI endpoint score) (1 RCT, n = 49, MD 0.13, 95% CI -0.30 to 0.55) or leaving the study early (2 RCTs, n = 141, RR 0.99, 95% CI 0.72 to 1.35), both very low-quality evidence. 6. perphenazineThose receiving zuclopenthixol were more likely to require medication in the short term for EPSEs than perphenazine (1 RCT, n = 50, RR 1.90, 95% CI 1.12 to 3.22, very low-quality evidence). Similar numbers left the study early (2 RCTs, n = 104, RR 0.63, 95% CI 0.27 to 1.47, very low-quality evidence). 7. risperidoneThose receiving zuclopenthixol were more likely to require medications for EPSEs than risperidone (1 RCT, n = 98,RR 1.92, 95% CI 1.12 to 3.28, very low quality evidence). There was no clear difference in numbers leaving the study early ( 3 RCTs, n = 154, RR 1.30, 95% CI 0.84 to 2.02) or in mental state (average PANSS total endpoint score) (1 RCT, n = 25, MD -3.20, 95% CI -7.71 to 1.31), both very low-quality evidence). 8. sulpirideNo clear differences were found for global state (average CGI endpoint score) ( 1 RCT, n = 61, RR 1.18, 95% CI 0.49 to 2.85, very low-quality evidence), requiring hypnotics/sedatives (1 RCT, n = 61, RR 0.60, 95% CI 0.27 to 1.32, very low-quality evidence) or leaving the study early (1 RCT, n = 61, RR 2.07 95% CI 0.97 to 4.40, very low-quality evidence). 9. thiothixeneNo clear differences were found for the outcomes of 'global state (average CGI endpoint score) (1 RCT, n = 20, RR 0.50, 95% CI 0.17 to 1.46) or leaving the study early (1 RCT, n = 20, RR 0.57, 95% CI 0.24 to 1.35), both very low-quality evidence). 10. trifluoperazineNo useable data were presented. 11. zuclopenthixol depotThere was no clear difference in numbers leaving the study early (1 RCT, n = 46, RR 1.95, 95% CI 0.36 to 10.58, very low-quality evidence). 12. Zuclopenthixol dihydrochloride (cis z isomer) versus zuclopenthixol (cis z/trans e isomer)There were no clear differences in reported side-effects ( 1 RCT, n = 57, RR 1.34, 95% CI 0.82 to 2.18, very low-quality evidence) and in numbers leaving the study early (4 RCTs, n = 140, RR 2.15, 95% CI 0.49 to 9.41, very low-quality evidence).
AUTHORS' CONCLUSIONS
Zuclopenthixol dihydrochloride appears to cause more EPSEs than clozapine, risperidone or perphenazine, but there was no difference in EPSEs when compared to placebo or chlorpromazine. Similar numbers required hypnotics/sedatives when zuclopenthixol dihydrochloride was compared to sulpiride, and similar numbers of reported side-effects were found when its isomers were compared. The other comparisons did not report adverse-effect data.Reported data indicate zuclopenthixol dihydrochloride demonstrates no difference in mental or global states compared to placebo, chlorpromazine, chlorprothixene, clozapine, haloperidol, perphenazine, sulpiride, thiothixene, trifluoperazine, depot and isomers. Zuclopenthixol dihydrochloride, when compared with risperidone, is favoured when assessed using the PANSS in the short term, but not in the medium term.The data extracted from the included studies are mostly equivocal, and very low to low quality, making it difficult to draw firm conclusions. Prescribing practice is unlikely to change based on this meta-analysis. Recommending any particular course of action about side-effect medication other than monitoring, using rating scales and clinical assessment, and prescriptions on a case-by-case basis, is also not possible.There is a need for further studies covering this topic with more antipsychotic comparisons for currently relevant outcomes.
Topics: Antipsychotic Agents; Clopenthixol; Humans; Movement Disorders; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 29144549
DOI: 10.1002/14651858.CD005474.pub2 -
The Cochrane Database of Systematic... 2004Treatment of people with schizophrenia using older typical antipsychotic drugs such as haloperidol can be problematic. Many fail to respond and more experience disabling... (Review)
Review
BACKGROUND
Treatment of people with schizophrenia using older typical antipsychotic drugs such as haloperidol can be problematic. Many fail to respond and more experience disabling adverse effects. Aripiprazole is said to be one of a new generation of atypical antipsychotics with good antipsychotic properties and minimal adverse effects.
OBJECTIVES
To evaluate the effects of aripiprazole for people with schizophrenia and schizophrenia-like psychoses.
SEARCH STRATEGY
The reviewers searched the Cochrane Schizophrenia Group's Register (May 2003) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. The authors contacted relevant pharmaceutical companies, the FDA and authors of trials for additional information.
SELECTION CRITERIA
All clinical randomised trials comparing aripiprazole with placebo, typical or atypical antipsychotic drugs for schizophrenia and schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD).
MAIN RESULTS
Despite the fact that 4125 people participated in ten randomised aripiprazole studies, we were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning. Study attrition was very large and data reporting poor. Compared with placebo, aripiprazole significantly decreased relapse in both the short and medium term (n=300, 1 RCT, RR 0.66 CI 0.53 to 0.81, NNT 5 CI 4 to 8). It also produced better compliance with study protocol (n=1348, 5 RCTs, RR 0.66 CI 0.49 to 0.88, NNT 15 CI 10 to 41). Aripiprazole may decrease prolactin levels below that expected from placebo (n=305, 1 RCT, RR 0.32 CI 0.13 to 0.81, NNT 14 CI 11 to 50). Compared with typical antipsychotics there were no significant benefits for aripiprazole with regards to global state, mental state, quality of life or leaving the study early. Both groups reported similar rates of adverse effects, including akathisia (RR 0.44 CI 0.17 to 1.12) and general extrapyramidal effects (RR 0.53 CI 0.18 to 1.53). Aripiprazole did however cause more insomnia than perphenazine (n=300, 1 RCT, RR 2.23 CI 1.57 to 3.18, NNH 4 CI 3 to 9) and less need for antiparkinson drugs than 10-20mg/day haloperidol (n=1854, 4 RCTs, RR 0.45 CI 0.33 to 0.60, NNT 4 CI 3 to 5). When compared with olanzapine and risperidone, aripiprazole was no better or worse on outcomes of global state and leaving the study early. The rates of adverse effects were also similar, with the exception of less elevation of prolactin (n=301, 1 RCT, RR 0.04 CI 0.02 to 0.08, NNT 2) and less prolongation of the average QTc (30mg/day) (n=200, 1 RCT, WMD -10.0, CI -16.99 to -3.01) compared with risperidone.
REVIEWERS' CONCLUSIONS
Aripiprazole may be effective for the treatment of schizophrenia, but it is not much different from typical antipsychotics and atypical antipsychotics with respect to treatment response, efficacy or tolerability. In comparison with typical antipsychotics, aripiprazole may have a higher risk of insomnia, but in comparison to atypical antipsychotics, less risk of raised prolactin and prolongation of the QTc interval. Clearly reported pragmatic short, medium and long term randomised controlled trials should be carried out to determine its position in everyday clinical practice.
Topics: Antipsychotic Agents; Aripiprazole; Humans; Piperazines; Quinolones; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 15106256
DOI: 10.1002/14651858.CD004578.pub2 -
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 -
Journal of Applied Toxicology : JAT Apr 2023In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the... (Review)
Review
In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the treatment of schizophrenia, which is related to altered neurotransmission and dysregulation of neuronal autophagy. Thus, phenothiazine derivatives can impact autophagy. We identified 35 papers, where the use of the phenothiazines in the in vitro autophagy assays on normal and cancer cell lines, Caenorhabditis elegans, and zebrafish were discussed. Chlorpromazine, fluphenazine, mepazine, methotrimeprazine, perphenazine, prochlorperazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate autophagy. Stimulation of autophagy by phenothiazines may be either mammalian target of rapamycin (mTOR)-dependent or mTOR-independent. The final effect depends on the used concentration as well as the cell line. A further investigation of the mechanisms of autophagy regulation by phenothiazine derivatives is required to understand the biological actions and to increase the therapeutic potential of this class of drugs.
Topics: Animals; Antipsychotic Agents; Zebrafish; Promazine; Phenothiazines; Chlorpromazine; Mammals
PubMed: 36165981
DOI: 10.1002/jat.4397 -
The Cochrane Database of Systematic... Jul 2007Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to... (Review)
Review
BACKGROUND
Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to promote additional response. The antiepileptic carbamazepine is one such drug.
OBJECTIVES
To evaluate the effects of carbamazepine and its derivatives for the treatment of schizophrenia and related psychoses.
SEARCH STRATEGY
For the original version we searched Biological Abstracts (1980-2001), The Cochrane Library (Issue 3, 2001), The Cochrane Schizophrenia Group's Register of Trials (December 2001), EMBASE (1980-2001), MEDLINE (1966-2001), PsycLIT (1886-2001) and PSYNDEX (1974-2001). For the current update we searched the Cochrane Schizophrenia Group's Register of Trials in March 2005 and in December 2006. We also inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors for additional data.
SELECTION CRITERIA
We included all randomised controlled trials comparing carbamazepine or compounds of the carbamazepine family to placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD).
MAIN RESULTS
The update search did not reveal any further studies that met our inclusion criteria. The number of included studies therefore remains at ten with the number of participants randomised still 258. One study comparing carbamazepine with placebo as the sole treatment for schizophrenia was abandoned early due to high relapse rate with 26 out of 31 participants relapsing by three months. No effect of carbamazepine was evident with no difference in relapse between the two groups (1 RCT n=31, RR 4.1 CI 0.8 to 1.5). Another study compared carbamazepine with antipsychotics as the sole treatment for schizophrenia. No differences in terms of mental state were found when comparing 50% reduction in BPRS scores (1 RCT n=38, RR 1.2 CI 0.8 to 1.9). A favourable effect for carbamazepine was found when more people who received the antipsychotic (perphenazine) had parkinsonism (1 RCT n=38, RR 0.03 CI 0.00 to 0.04, NNH 1 CI 0.9 to 1.4). Eight studies compared adjunctive carbamazepine versus adjunctive placebo. Adding carbamazepine to antipsychotic treatment was as acceptable as adding placebo with no difference between the numbers leaving the study early from each group (8 RCTs n=182, RR 0.5 CI 0.2 to 1.4). Carbamazepine augmentation was superior compared with antipsychotics alone in terms of overall global improvement, but participant numbers were low (2RCTs n=38, RR 0.6 CI 0.4 to 0.9, NNT 2 CI 1 to 5). There were no differences for the mental state outcome of 50% reduction in BPRS scores (6 RCTs n=147, RR 0.9 CI 0.7 to 1.1). Less people in the carbamazepine augmentation group had movement disorders than those taking haloperidol alone (1 RCT n=20, RR 0.4 CI 0.1 to 1.0). No data were available for the effects of carbamazepine on subgroups of people with schizophrenia and aggressive behaviour, negative symptoms or EEG abnormalities or with schizoaffective disorder.
AUTHORS' CONCLUSIONS
Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommended for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. At present large, simple well-designed and reported trials are justified especially if focusing on those with violent episodes and people with schizoaffective disorders or those with both schizophrenia and EEG abnormalities.
Topics: Antimanic Agents; Carbamazepine; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 17636660
DOI: 10.1002/14651858.CD001258.pub2 -
Nederlands Tijdschrift Voor Geneeskunde Jul 2006To assess the efficacy and adverse reactions of typical and atypical antipsychotics in the treatment of neuropsychiatric symptoms in dementia, and to examine the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy and adverse reactions of typical and atypical antipsychotics in the treatment of neuropsychiatric symptoms in dementia, and to examine the evidence for the cerebrovascular events warning for atypical antipsychotics.
DESIGN
Systematic review.
METHOD
Using Medline, Cinahl, PsyclNFO, Embase and the Cochrane central register of controlled trials (1980-2005), double-blind randomized controlled trials with intention-to-treat analysis were selected, which evaluated efficacy and adverse reactions of antipsychotics in the treatment of neuropsychiatric symptoms in dementia. The studies underwent a standardised validity assessment.
RESULTS
After screening 950 studies, 14 studies on the effect of haloperidol, risperidone, olanzapine, quetiapine, tiapride, loxapine and perphenazine were selected. In 7 out of 10 studies, haloperidol, risperidone and olanzapine appeared to be more effective than placebo in the treatment of aggression and psychosis. Direct comparison between typical and atypical antipsychotics revealed no statistically significant difference. The most common adverse reactions were extrapyramidal symptoms and somnolence. These adverse reactions were less frequent with low-dose risperidone than with haloperidol or olanzapine, but risperidone and olanzapine were found to be associated with a higher risk of cerebrovascular events in two studies.
CONCLUSION
The efficacy of typical and atypical antipsychotics is comparable, but only low-dose risperidone seems to be associated with fewer (extrapyramidal) side effects. The adverse reactions are inadequately described in the published data and consequently the warning of an increased risk of mortality could not be confirmed.
Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Dementia; Haloperidol; Humans; Olanzapine; Psychotic Disorders; Risperidone; Treatment Outcome
PubMed: 16886695
DOI: No ID Found