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BMJ Clinical Evidence Oct 2011Up to one in five people may have generalised anxiety disorder (GAD) at some point, and most have other health problems. Less than half of people have full remission... (Review)
Review
INTRODUCTION
Up to one in five people may have generalised anxiety disorder (GAD) at some point, and most have other health problems. Less than half of people have full remission after 5 years. GAD may have a genetic component, and has also been linked to previous psychological or other trauma.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for GAD? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 74 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: abecarnil, antidepressants (duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, opipramol, paroxetine, sertraline, and venlafaxine), antipsychotic drugs (trifluoperazine), applied relaxation, benzodiazepines, buspirone, cognitive behavioural therapy, hydroxyzine, and pregabalin.
Topics: Anxiety Disorders; Benzodiazepines; Buspirone; Humans; Hydroxyzine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 22030083
DOI: No ID Found -
BMJ Clinical Evidence Nov 2007Up to one in five people may have generalised anxiety disorder (GAD) at some point, and most have other health problems. Less than half of people have full remission... (Review)
Review
INTRODUCTION
Up to one in five people may have generalised anxiety disorder (GAD) at some point, and most have other health problems. Less than half of people have full remission after 5 years. GAD may have a genetic component, and has also been linked to previous psychological or other trauma.
METHODS AND OBJECTIVES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for GAD? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 52 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: abecarnil, antidepressants (imipramine, opipramol, paroxetine, sertraline, escitalopram and venlafaxine), antipsychotic drugs (trifluoperazine), applied relaxation, benzodiazepines, buspirone, cognitive behavioural therapy, hydroxyzine, kava, and pregabalin.
Topics: Anxiety Disorders; Citalopram; Cognitive Behavioral Therapy; Double-Blind Method; Humans; Paroxetine; Remission Induction; Sertraline
PubMed: 19450347
DOI: No ID Found -
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... 2004Trifluoperazine is an inexpensive accessible 'high potency' antipsychotic drug, widely used to treat schizophrenia or related psychoses. (Review)
Review
BACKGROUND
Trifluoperazine is an inexpensive accessible 'high potency' antipsychotic drug, widely used to treat schizophrenia or related psychoses.
OBJECTIVES
To estimate the effects of trifluoperazine compared with placebo and other drugs.
SEARCH STRATEGY
Searches of the Cochrane Schizophrenia Group's register of trials (March 2002), supplemented with hand searching, reference searching, personal communication and contact with industry.
SELECTION CRITERIA
All clinical randomised trials involving people with schizophrenia and comparing trifluoperazine with any other treatment.
DATA COLLECTION AND ANALYSIS
Studies were reliably selected and quality rated and data was extracted. For dichotomous data, relative risks (RR) were estimated, with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, the number needed to treat (NNT) was calculated. We estimated heterogeneity (I-square technique) and publication bias.
MAIN RESULTS
1162 people from 13 studies were randomised to trifluoperazine or placebo. For global improvement, small short-term studies favoured trifluoperazine (n=95, 3 RCTs, RR 0.62 CI 0.49 to 0.78 NNT 3 CI 2 to 4). Loss to follow up was about 12% in both groups (n=280, 7 RCTs, RR 0.99 CI 0.62 to 1.57) and more people allocated trifluoperazine used antiparkinson drugs to alleviate movements disorders compared with placebo (n=195, 4 RCTs, RR 5.06 CI 2.49 to 10.27, NNH 4 CI 2 to 9). 2230 people from 49 studies were randomised to trifluoperazine or another older generation antipsychotic. Trifluoperazine was not clearly different in terms of 'no substantial improvement' (n=1016, 27 RCTs, RR 1.06 CI 0.98 to 1.14) or leaving the study early (n=930, 22 RCTs, RR 1.15 CI 0.83 to 1.58). Almost identical numbers of people reported at least one adverse event (60%) in each group (n=585, 14 RCTs, RR 0.99 CI 0.87 to 1.13), although trifluoperazine was more likely to cause extrapyramidal adverse effects overall when compared to low potency antipsychotics such as chlorpromazine (n=130, 3 RCTs, RR 1.66 CI 1.03 to 2.67, NNH 6 CI 3 to 121). One small study (n=38) found no clear differences between trifluoperazine and the atypical drug, sulpiride.
REVIEWER'S CONCLUSIONS
Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that trifluoperazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs. It has been claimed that trifluoperazine is effective at low doses for patients with schizophrenia but this does not appear to be based on good quality trial based evidence.
Topics: Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Trifluoperazine
PubMed: 14974020
DOI: 10.1002/14651858.CD003545.pub2 -
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... Oct 2004Acute psychotic illnesses, especially when associated with agitated or violent behaviour, require urgent pharmacological tranquillisation or sedation. Clotiapine, a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute psychotic illnesses, especially when associated with agitated or violent behaviour, require urgent pharmacological tranquillisation or sedation. Clotiapine, a dibenzothiazepine neuroleptic, is being used for this purpose in several countries.
OBJECTIVES
To estimate the effects of clotiapine when compared to other 'standard' or 'non-standard' treatments for acute psychotic illnesses in controlling disturbed behaviour and reducing psychotic symptoms.
SEARCH STRATEGY
We updated previous searches by searching the Cochrane Schizophrenia Group Register (April 2004)
SELECTION CRITERIA
The review included randomised clinical trials comparing clotiapine with any other treatment for people with acute psychotic illnesses.
DATA COLLECTION AND ANALYSIS
Relevant studies were selected for inclusion, their quality was assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes we calculated a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD).
MAIN RESULTS
We identified five relevant trials. None compared clotiapine with placebo, but control drugs were either antipsychotics (chlorpromazine, perphenazine, trifluoperazine and zuclopenthixol acetate) or benzodiazepines (lorazepam). Versus the antipsychotics, the results for 'no important global improvement' did not suggest clotiapine to be superior, or inferior, to chlorpromazine, perphenazine, or trifluoperazine (n = 83, 3 RCTs, RR 0.82 CI 0.22 to 3.05, I-squared 58%). Use of clotiapine when compared with chlorpromazine did change the proportion of people ready for hospital discharge by the end of the study (n = 49, 1 RCT, RR 1.04 95%CI 0.96 to 2.12). Overall, attrition rates were low. No significant difference was found for those allocated to clotiapine compared with people randomised to other antipsychotics (n = 121, RR 2.26 95%CI 0.40 to 13). Weak data suggests that clotiapine may result in less need for antiparkinsonian treatment compared with zuclopenthixol acetate (n = 38, RR 0.43 95%CI 0.02 to 0.98). Compared with lorazepam, clotiapine, when used to control aggressive/violent outbursts for people already treated with haloperidol, did not significantly improve mental state (WMD -3.36 95%CI -8.09 to 1.37). We could not pool much data due to skew or inadequate presentation of results. Economic outcomes and satisfaction with care were not addressed.
REVIEWERS' CONCLUSIONS
We found no evidence to support the use of clotiapine in preference to other 'standard' or 'non-standard' treatments for management of people with acute psychotic illness. All trials in this review have important methodological problems. We do not wish to discourage clinicians from using clotiapine in the psychiatric emergency, but well-designed, conducted and reported trials are needed to properly determine the efficacy of this drug.
Topics: Acute Disease; Antipsychotic Agents; Dibenzothiazepines; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 15495032
DOI: 10.1002/14651858.CD002304.pub2 -
The Cochrane Database of Systematic... Jun 2011Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment.
OBJECTIVES
To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data.
SELECTION CRITERIA
Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment.
DATA COLLECTION AND ANALYSIS
Working independently, we critically appraised records from 681studies, of which five studies met inclusion criteria. John Rathbone from the Schizophrenia Group supported us with the data extraction. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate.
MAIN RESULTS
Five studies with a combined N = 998 met inclusion criteria. Four studies (N = 724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs N = 353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT N = 240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT N = 236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT N = 94, RR 0.96 CI 0.3 to 3.6). Two studies (Cole 1964; May 1976) contributed data to assessment of side effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications compared to placebo. Rappaport 1978 suggested a higher rehospitalisation rate for those receiving chlorpromazine compared to placebo (N = 80, RR 2.29 CI 1.3 to 4.0, NNH 2.9). However, a higher attrition in the placebo group is likely to have introduced a survivor bias into this comparison, as this difference becomes non-significant in a sensitivity analysis on intent-to-treat participants (N = 127, RR 1.69 CI 0.9 to 3.0). One study (May 1976) contributes data to a comparison of trifluoperazine to psychotherapy on long-term health in favour of the trifluoperazine group (N = 92, MD 5.8 CI 1.6 to 0.0); however, data from this study are also likely to contain biases due to selection and attrition. One study (Mosher 1995) contributes data to a comparison of typical antipsychotic medication to psychosocial treatment on six-week outcome measures of global psychopathology (N = 89, MD 0.01 CI -0.6 to 0.6) and global improvement (N = 89, MD -0.03 CI -0.5 to 0.4), indicating no between-group differences. On the whole, there is very little useable data in the few studies meeting inclusion criteria.
AUTHORS' CONCLUSIONS
With only a few studies meeting inclusion criteria, and with limited useable data in these studies, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that people with early episode schizophrenia treated with typical antipsychotic medications are less likely to leave the study early, but more likely to experience medication-related side effects. Data are too sparse to assess the effects of antipsychotic medication on outcomes in early episode schizophrenia.
Topics: Antipsychotic Agents; Chlorpromazine; Fluphenazine; Humans; Patient Dropouts; Randomized Controlled Trials as Topic; Schizophrenia; Thioridazine; Trifluoperazine
PubMed: 21678355
DOI: 10.1002/14651858.CD006374.pub2 -
The Cochrane Database of Systematic... Jan 2015Haloperidol is worldwide one of the most frequently used antipsychotic drugs with a very high market share. Previous narrative, unsystematic reviews found no differences... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Haloperidol is worldwide one of the most frequently used antipsychotic drugs with a very high market share. Previous narrative, unsystematic reviews found no differences in terms of efficacy between the various first-generation ("conventional", "typical") antipsychotic agents. This established the unproven psychopharmacological assumption of a comparable efficacy between the first-generation antipsychotic compounds codified in textbooks and treatment guidelines. Because this assumption contrasts with the clinical impression, a high-quality systematic review appeared highly necessary.
OBJECTIVES
To compare the efficacy, acceptability, and tolerability of haloperidol with other first-generation antipsychotics in schizophrenia and schizophrenia-like psychosis.
SEARCH METHODS
In October 2011 and July 2012, we searched the Cochrane Schizophrenia Group's Trials Register, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. To identify further relevant publications, we screened the references of all included studies and contacted the manufacturers of haloperidol for further relevant trials and missing information on identified studies. Furthermore, we contacted the corresponding authors of all included trials for missing data.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) that compared oral haloperidol with another oral first-generation antipsychotic drug (with the exception of the low-potency antipsychotics chlorpromazine, chlorprothixene, levopromazine, mesoridazine, perazine, prochlorpromazine, and thioridazine) in schizophrenia and schizophrenia-like psychosis. Clinically important response to treatment was defined as the primary outcome. Secondary outcomes were global state, mental state, behaviour, overall acceptability (measured by the number of participants leaving the study early due to any reason), overall efficacy (attrition due to inefficacy of treatment), overall tolerability (attrition due to adverse events), and specific adverse effects.
DATA COLLECTION AND ANALYSIS
At least two review authors independently extracted data from the included trials. The methodological quality of the included studies was assessed using The Cochrane Collaboration`s 'Risk of bias' tool.We analysed dichotomous outcomes with risk ratios (RR) and continuous outcomes with mean differences (MD), both with the associated 95% confidence intervals (CI). All analyses were based on a random-effects model and we preferably used data on an intention-to-treat basis where possible.
MAIN RESULTS
The systematic review currently includes 63 randomised trials with 3675 participants. Bromperidol (n = 9), loxapine (n = 7), and trifluoperazine (n = 6) were the most frequently administered antipsychotics comparator to haloperidol. The included studies were published between 1962 and 1993, were characterised by small sample sizes (mean: 58 participants, range from 18 to 206) and the predefined outcomes were often incompletely reported. All results for the main outcomes were based on very low or low quality data. In many trials the mechanism of randomisation, allocation, and blinding was frequently not reported. In short-term studies (up to 12 weeks), there was no clear evidence of a difference between haloperidol and the pooled group of the other first-generation antipsychotic agents in terms of the primary outcome "clinically important response to treatment" (40 RCTs, n = 2132, RR 0.93 CI 0.87 to 1.00). In the medium-term trials, haloperidol may be less effective than the other first-generation antipsychotic group but this evidence is based on only one trial (1 RCT, n = 80, RR 0.51 CI 0.37 to 0.69).Based on limited evidence, haloperidol alleviated more positive symptoms of schizophrenia than the other antipsychotic drugs. There were no statistically significant between-group differences in global state, other mental state outcomes, behaviour, leaving the study early due to any reason, due to inefficacy, as well as due to adverse effects. The only statistically significant difference in specific side effects was that haloperidol produced less akathisia in the medium term.
AUTHORS' CONCLUSIONS
The findings of the meta-analytic calculations support the statements of previous narrative, unsystematic reviews suggesting comparable efficacy of first-generation antipsychotics. In efficacy-related outcomes, there was no clear evidence of a difference between the prototypal drug haloperidol and other, mainly high-potency first-generation antipsychotics. Additionally, we demonstrated that haloperidol is characterised by a similar risk profile compared to the other first-generation antipsychotic compounds. The only statistically significant difference in specific side effects was that haloperidol produced less akathisia in the medium term. The results were limited by the low methodological quality in many of the included original studies. Data for the main results were low or very low quality. Therefore, future clinical trials with high methodological quality are required.
Topics: Administration, Oral; Antipsychotic Agents; Haloperidol; Humans; Loxapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Trifluoperazine
PubMed: 25592299
DOI: 10.1002/14651858.CD009831.pub2 -
Cells Oct 2021The incidence of spinal cord injury (SCI) is ever-growing, resulting in life-changing neurological deficits which can have devastating long-term impacts on a person's... (Meta-Analysis)
Meta-Analysis
The incidence of spinal cord injury (SCI) is ever-growing, resulting in life-changing neurological deficits which can have devastating long-term impacts on a person's quality of life. There is an unmet clinical need for a treatment which will prevent progression of the injury, allowing improved axonal regeneration and functional recovery to occur. The initial mechanical insult, followed by a cascade of secondary mechanisms, leads to the exacerbation and remodelling of the lesion site, thus inhibiting neurological recovery. Oedema rapidly accumulates following SCI and contributes to the detrimental pathophysiology and worsens functional outcomes. This study systematically reviewed the current experimental treatments being explored in the field of SCI, which specifically target oedema. Abiding by PRISMA guidelines and strict inclusion criteria, 14 studies were identified and analysed from three online databases (PubMed, Web of Science and EMBASE). As a result, we identified three key modalities which attenuate oedema: selective inhibition of the main water channel protein, aquaporin 4 (AQP4), modulation of inflammation and surgical interventions. Collectively, however, they all result in the downregulation of AQP4, which crucially leads to a reduction in oedema and improved functional outcomes. We concluded that trifluoperazine (TFP), a calmodulin kinase inhibitor which prevents the cell-surface localisation of AQP4, was the most efficacious treatment, significantly eliminating oedema within 7 days of administration. To date, this study is the most concise analysis of current experimental treatments for oedema, exposing its molecular mechanisms and assessing potential therapeutic pathways for future research.
Topics: Animals; Blood-Brain Barrier; Edema; Humans; Motor Activity; Publication Bias; Rats; Recovery of Function; Risk; Spinal Cord Injuries; Treatment Outcome
PubMed: 34685662
DOI: 10.3390/cells10102682 -
BJPsych Open Jan 2016For treatment of patients diagnosed with schizophrenia, comparative long-term effectiveness of antipsychotic drugs to reduce relapses when minimising adverse effects is...
BACKGROUND
For treatment of patients diagnosed with schizophrenia, comparative long-term effectiveness of antipsychotic drugs to reduce relapses when minimising adverse effects is of clinical interest, hence prompting this review.
AIMS
To evaluate the comparative long-term effectiveness of antipsychotic drugs.
METHOD
We systematically searched electronic databases for reports of randomised controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing relapse risks in schizophrenia. We conducted network meta-analysis of 18 antipsychotics and placebo.
RESULTS
Studies of 10 177 patients in 56 reports were included; treatment duration averaged 48 weeks (range 4-156). Olanzapine was significantly more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI 0.14-0.88) or haloperidol (OR=0.50, 95% CI 0.30-0.82); and fluphenazine decanoate was more effective than chlorpromazine (OR=0.31, 95% CI 0.11-0.88) in relapse reduction. Fluphenazine decanoate, haloperidol, haloperidol decanoate and trifluoperazine produced more extrapyramidal adverse effects than olanzapine or quetiapine; and olanzapine was associated with more weight gain than other agents.
CONCLUSIONS
Except for apparent superiority of olanzapine and fluphenazine decanoate over chlorpromazine, most agents showed intermediate efficacy for relapse prevention and differences among them were minor. Typical antipsychotics yielded adverse neurological effects, and olanzapine was associated with weight gain. The findings may contribute to evidence-based treatment selection for patients with chronic psychotic disorders.
DECLARATION OF INTEREST
R.J.B. received grants from the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology Research Fund.
COPYRIGHT AND USAGE
© The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
PubMed: 27703755
DOI: 10.1192/bjpo.bp.115.002576