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Stefan Leucht - One of the best experts on this subject based on the ideXlab platform.
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The Cochrane Library - Haloperidol versus First-Generation Antipsychotics for the treatment of schizophrenia and other psychotic disorders.
Cochrane Database of Systematic Reviews, 2015Co-Authors: Markus Dold, Magdolna Tardy, Myrto Samara, Stefan LeuchtAbstract: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.
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Perphenazine versus low-potency First-Generation Antipsychotic drugs for schizophrenia.
The Cochrane database of systematic reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract: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. To review the effects of high-potency, First-Generation perphenazine compared with low-potency, First-Generation Antipsychotic drugs for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (October 2010). We included all randomised controlled trials (RCTs) comparing perphenazine with First-Generation, low-potency Antipsychotic drugs for people with schizophrenia or schizophrenia-like psychoses. 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. 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. 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.
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Flupenthixol versus low-potency First-Generation Antipsychotic drugs for schizophrenia.
The Cochrane database of systematic reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Markus Dold, Stefan LeuchtAbstract:Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between Antipsychotic drugs, however, low-potency Antipsychotic drugs are sometimes perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects. To review the effects in clinical response of flupenthixol and low-potency Antipsychotics for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (July 2010). Randomised controlled trials that compared flupenthixol with First-Generation low-potency Antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For continuous data, we calculated mean differences (MD) based on a random-effects model. The review currently includes one randomised trial from mainland China with 153 participants that lasted two months and compared flupenthixol with chlorpromazine. The exact methods of sequence Generation and allocation concealment were not reported, and medication was provided in an open manner. There were no data on the outcomes that we had a priori selected for a 'Summary of findings' table.There was no significant difference between flupenthixol and chlorpromazine in the participants' general mental state at endpoint as measured by the Brief Psychiatric Rating Scale (BPRS) total score (1 randomised controlled trial (RCT), n = 153, MD 2.20 95% confidence interval (CI) -1.25 to 5.65). Chlorpromazine was associated with significantly less dizziness (1 RCT, n = 153, MD 0.12 95% CI 0.01 to 0.23); dystonia (1 RCT, n = 153, MD 0.29 95% CI 0.13 to 0.45); unsteady gait (1 RCT, n = 153, MD 0.46 95% CI 0.28 to 0.64); reduced facial expression (1 RCT, n = 153, MD 0.27 95% CI 0.09 to 0.45); restlessness (1 RCT, n = 153, MD 0.69 95% CI 0.45 to 0.93); rigidity (elbow) (1 RCT, n = 153, MD 0.48 95% CI 0.28 to 0.68); and tremor (1 RCT, n = 153, MD 0.56 95% CI 0.34 to 0.78). Chlorpromazine produced more dryness of mouth than flupenthixol (1 RCT, n = 153, MD -0.14 95% CI -0.25 to -0.03). The evidence base of flupenthixol versus low-potency First-Generation Antipsychotics is currently restricted to one randomised comparison with chlorpromazine. The few reported data do not suggest a difference in efficacy, but flupenthixol appeared to produce more movement disorders and dizziness, while chlorpromazine was associated with the anticholinergic side effect - dryness of mouth. More trials are needed to make conclusions about the relative effects of flupenthixol and low-potency Antipsychotics.
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Fluphenazine versus low-potency First-Generation Antipsychotic drugs for schizophrenia.
The Cochrane database of systematic reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract:Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between any other Antipsychotic compounds, however, low-potency Antipsychotic drugs are often perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects. This review examined the effects of the high-potency Antipsychotic fluphenazine compared to those of low-potency Antipsychotics. To review the effects of fluphenazine and low-potency Antipsychotics for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (November 2010). We included all randomised controlled trials (RCTs) comparing fluphenazine with First-Generation low-potency Antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. The review currently includes seven randomised trials and 1567 participants that compared fluphenazine with low-potency Antipsychotic drugs. The size of the included studies was between 40 and 438 participants. Overall, sequence Generation, allocation procedures and blinding were poorly reported. Fluphenazine was not significantly different from low-potency Antipsychotic drugs in terms of response to treatment (fluphenazine 55%, low-potency drug 55%, 2 RCTs, n = 105, RR 1.06 CI 0.75 to 1.50, moderate quality evidence). There was also no significant difference in acceptability of treatment with equivocal numbers of participants leaving the studies early due to any reason (fluphenazine 36%, low-potency Antipsychotics 36%, 6 RCTs, n = 1532, RR 1.00 CI 0.88 to 1.14, moderate quality evidence). There was no significant difference between fluphenazine and low-potency Antipsychotics for numbers experiencing at least one adverse effect (fluphenazine 70%, low-potency Antipsychotics 88%, 1 RCT, n = 65, RR 0.79 CI 0.58 to 1.07, moderate quality evidence). However, at least one movement disorder occurred significantly more frequently in the fluphenazine group (fluphenazine 15%, low-potency Antipsychotics 10%, 3 RCTs, n = 971, RR 2.11 CI 1.41 to 3.15, low quality of evidence). In contrast, low-potency Antipsychotics produced significantly more sedation (fluphenazine 20%, low-potency Antipsychotics 64%, 1 RCT, n = 65, RR 0.31 CI 0.13 to 0.77, high quality evidence). No data were available for the outcomes of death and quality of life. The results of the primary outcome were robust in a number of subgroup and sensitivity analyses.Adverse effects such as akathisia (fluphenazine 15%, low-potency Antipsychotics 6%, 5 RCTs, n = 1209, RR 2.28 CI 1.58 to 3.28); dystonia (fluphenazine 5%, low-potency Antipsychotics 2%, 4 RCTs, n = 1309, RR 2.66 CI 1.25 to 5.64); loss of associated movement (fluphenazine 20%, low-potency Antipsychotics 2%, 1 RCT, n = 338, RR 11.15 CI 3.95 to 31.47); rigor (fluphenazine 27%, low-potency Antipsychotics 12%, 2 RCTs, n = 403, RR 2.18 CI 1.20 to 3.97); and tremor (fluphenazine 15%, low-potency Antipsychotics 6%, 2 RCTs, n = 403, RR 2.53 CI 1.37 to 4.68) occurred significantly more frequently in the fluphenazine group.For other adverse effects such as dizziness (fluphenazine 8%, low-potency Antipsychotics 17%, 4 RCTs, n = 1051, RR 0.49 CI 0.32 to 0.73); drowsiness (fluphenazine 18%, low-potency Antipsychotics 25%, 3 RCTs, n = 986, RR 0.67 CI 0.53 to 0.86); dry mouth (fluphenazine 11%, low-potency Antipsychotics 18%, 4 RCTs, n = 1051, RR 0.63 CI 0.45 to 0.89); nausea (fluphenazine 4%, low-potency Antipsychotics 15%, 3 RCTs, n = 986, RR 0.25 CI 0.14 to 0.45); and vomiting (fluphenazine 3%, low-potency Antipsychotics 8%, 3 RCTs, n = 986, RR 0.36 CI 0.18 to 0.72) results favoured fluphenazine with significantly more events occurring in the low-potency Antipsychotic group for these outcomes. The results do not show a clear difference in efficacy between fluphenazine and low-potency Antipsychotics. The number of included studies was low and their quality moderate. Therefore, further studies would be needed to draw firm conclusions about the relative effects of fluphenazine and low-potency Antipsychotics.
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haloperidol versus low potency First Generation Antipsychotic drugs for schizophrenia
Cochrane Database of Systematic Reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract:People with schizophrenia often hear voices or see things (hallucinations) and have strange beliefs (delusions). It is a serious, often long lasting, mental illness that can have a severe detrimental effect on all aspects of the sufferer's life. Antipsychotic drugs are the main treatment for the symptoms of schizophrenia. Fluphenazine is an older Antipsychotic that is effective in treating the symptoms of schizophrenia. However, most Antipsychotics have side effects and when compared to newer Antipsychotic drugs, fluphenazine is thought to be more likely to cause serious movement disorders such as involuntary shaking, tremors, muscle stiffness and the inability to sit still. Fluphenazine is also known to lower people’s mood. Prescribing low-strength or low-potency drugs can help reduce side effects but are often seen as less effective in treating symptoms. This review examined the effects of the high-potency Antipsychotic fluphenazine compared with those of low-potency Antipsychotics. A search for randomised trials comparing these types of drugs was carried out in 2010. The review includes seven studies with 1567 participants. Pooled data from two of these trials did not show a clear difference in effectiveness between fluphenazine and low-potency Antipsychotics. However, evidence showed fluphenazine produced more movement disorders than low-potency Antipsychotics, whereas the low-potency drugs were more likely to cause dizziness, drowsiness and sedation, a dry mouth, nausea and sometimes even vomiting. The number of included studies was low and the quality of evidence provided was moderate. Therefore, further good quality studies would be needed to draw firm conclusions about the relative effectiveness of fluphenazine compared to low-potency Antipsychotics. Important information on service use, going into hospital again (rehospitalisation), costs and quality of life was missing and not reported.
Rolf R. Engel - One of the best experts on this subject based on the ideXlab platform.
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Perphenazine versus low-potency First-Generation Antipsychotic drugs for schizophrenia.
The Cochrane database of systematic reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract: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. To review the effects of high-potency, First-Generation perphenazine compared with low-potency, First-Generation Antipsychotic drugs for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (October 2010). We included all randomised controlled trials (RCTs) comparing perphenazine with First-Generation, low-potency Antipsychotic drugs for people with schizophrenia or schizophrenia-like psychoses. 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. 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. 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.
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Flupenthixol versus low-potency First-Generation Antipsychotic drugs for schizophrenia.
The Cochrane database of systematic reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Markus Dold, Stefan LeuchtAbstract:Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between Antipsychotic drugs, however, low-potency Antipsychotic drugs are sometimes perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects. To review the effects in clinical response of flupenthixol and low-potency Antipsychotics for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (July 2010). Randomised controlled trials that compared flupenthixol with First-Generation low-potency Antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For continuous data, we calculated mean differences (MD) based on a random-effects model. The review currently includes one randomised trial from mainland China with 153 participants that lasted two months and compared flupenthixol with chlorpromazine. The exact methods of sequence Generation and allocation concealment were not reported, and medication was provided in an open manner. There were no data on the outcomes that we had a priori selected for a 'Summary of findings' table.There was no significant difference between flupenthixol and chlorpromazine in the participants' general mental state at endpoint as measured by the Brief Psychiatric Rating Scale (BPRS) total score (1 randomised controlled trial (RCT), n = 153, MD 2.20 95% confidence interval (CI) -1.25 to 5.65). Chlorpromazine was associated with significantly less dizziness (1 RCT, n = 153, MD 0.12 95% CI 0.01 to 0.23); dystonia (1 RCT, n = 153, MD 0.29 95% CI 0.13 to 0.45); unsteady gait (1 RCT, n = 153, MD 0.46 95% CI 0.28 to 0.64); reduced facial expression (1 RCT, n = 153, MD 0.27 95% CI 0.09 to 0.45); restlessness (1 RCT, n = 153, MD 0.69 95% CI 0.45 to 0.93); rigidity (elbow) (1 RCT, n = 153, MD 0.48 95% CI 0.28 to 0.68); and tremor (1 RCT, n = 153, MD 0.56 95% CI 0.34 to 0.78). Chlorpromazine produced more dryness of mouth than flupenthixol (1 RCT, n = 153, MD -0.14 95% CI -0.25 to -0.03). The evidence base of flupenthixol versus low-potency First-Generation Antipsychotics is currently restricted to one randomised comparison with chlorpromazine. The few reported data do not suggest a difference in efficacy, but flupenthixol appeared to produce more movement disorders and dizziness, while chlorpromazine was associated with the anticholinergic side effect - dryness of mouth. More trials are needed to make conclusions about the relative effects of flupenthixol and low-potency Antipsychotics.
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Fluphenazine versus low-potency First-Generation Antipsychotic drugs for schizophrenia.
The Cochrane database of systematic reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract:Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between any other Antipsychotic compounds, however, low-potency Antipsychotic drugs are often perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects. This review examined the effects of the high-potency Antipsychotic fluphenazine compared to those of low-potency Antipsychotics. To review the effects of fluphenazine and low-potency Antipsychotics for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (November 2010). We included all randomised controlled trials (RCTs) comparing fluphenazine with First-Generation low-potency Antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. The review currently includes seven randomised trials and 1567 participants that compared fluphenazine with low-potency Antipsychotic drugs. The size of the included studies was between 40 and 438 participants. Overall, sequence Generation, allocation procedures and blinding were poorly reported. Fluphenazine was not significantly different from low-potency Antipsychotic drugs in terms of response to treatment (fluphenazine 55%, low-potency drug 55%, 2 RCTs, n = 105, RR 1.06 CI 0.75 to 1.50, moderate quality evidence). There was also no significant difference in acceptability of treatment with equivocal numbers of participants leaving the studies early due to any reason (fluphenazine 36%, low-potency Antipsychotics 36%, 6 RCTs, n = 1532, RR 1.00 CI 0.88 to 1.14, moderate quality evidence). There was no significant difference between fluphenazine and low-potency Antipsychotics for numbers experiencing at least one adverse effect (fluphenazine 70%, low-potency Antipsychotics 88%, 1 RCT, n = 65, RR 0.79 CI 0.58 to 1.07, moderate quality evidence). However, at least one movement disorder occurred significantly more frequently in the fluphenazine group (fluphenazine 15%, low-potency Antipsychotics 10%, 3 RCTs, n = 971, RR 2.11 CI 1.41 to 3.15, low quality of evidence). In contrast, low-potency Antipsychotics produced significantly more sedation (fluphenazine 20%, low-potency Antipsychotics 64%, 1 RCT, n = 65, RR 0.31 CI 0.13 to 0.77, high quality evidence). No data were available for the outcomes of death and quality of life. The results of the primary outcome were robust in a number of subgroup and sensitivity analyses.Adverse effects such as akathisia (fluphenazine 15%, low-potency Antipsychotics 6%, 5 RCTs, n = 1209, RR 2.28 CI 1.58 to 3.28); dystonia (fluphenazine 5%, low-potency Antipsychotics 2%, 4 RCTs, n = 1309, RR 2.66 CI 1.25 to 5.64); loss of associated movement (fluphenazine 20%, low-potency Antipsychotics 2%, 1 RCT, n = 338, RR 11.15 CI 3.95 to 31.47); rigor (fluphenazine 27%, low-potency Antipsychotics 12%, 2 RCTs, n = 403, RR 2.18 CI 1.20 to 3.97); and tremor (fluphenazine 15%, low-potency Antipsychotics 6%, 2 RCTs, n = 403, RR 2.53 CI 1.37 to 4.68) occurred significantly more frequently in the fluphenazine group.For other adverse effects such as dizziness (fluphenazine 8%, low-potency Antipsychotics 17%, 4 RCTs, n = 1051, RR 0.49 CI 0.32 to 0.73); drowsiness (fluphenazine 18%, low-potency Antipsychotics 25%, 3 RCTs, n = 986, RR 0.67 CI 0.53 to 0.86); dry mouth (fluphenazine 11%, low-potency Antipsychotics 18%, 4 RCTs, n = 1051, RR 0.63 CI 0.45 to 0.89); nausea (fluphenazine 4%, low-potency Antipsychotics 15%, 3 RCTs, n = 986, RR 0.25 CI 0.14 to 0.45); and vomiting (fluphenazine 3%, low-potency Antipsychotics 8%, 3 RCTs, n = 986, RR 0.36 CI 0.18 to 0.72) results favoured fluphenazine with significantly more events occurring in the low-potency Antipsychotic group for these outcomes. The results do not show a clear difference in efficacy between fluphenazine and low-potency Antipsychotics. The number of included studies was low and their quality moderate. Therefore, further studies would be needed to draw firm conclusions about the relative effects of fluphenazine and low-potency Antipsychotics.
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haloperidol versus low potency First Generation Antipsychotic drugs for schizophrenia
Cochrane Database of Systematic Reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract:People with schizophrenia often hear voices or see things (hallucinations) and have strange beliefs (delusions). It is a serious, often long lasting, mental illness that can have a severe detrimental effect on all aspects of the sufferer's life. Antipsychotic drugs are the main treatment for the symptoms of schizophrenia. Fluphenazine is an older Antipsychotic that is effective in treating the symptoms of schizophrenia. However, most Antipsychotics have side effects and when compared to newer Antipsychotic drugs, fluphenazine is thought to be more likely to cause serious movement disorders such as involuntary shaking, tremors, muscle stiffness and the inability to sit still. Fluphenazine is also known to lower people’s mood. Prescribing low-strength or low-potency drugs can help reduce side effects but are often seen as less effective in treating symptoms. This review examined the effects of the high-potency Antipsychotic fluphenazine compared with those of low-potency Antipsychotics. A search for randomised trials comparing these types of drugs was carried out in 2010. The review includes seven studies with 1567 participants. Pooled data from two of these trials did not show a clear difference in effectiveness between fluphenazine and low-potency Antipsychotics. However, evidence showed fluphenazine produced more movement disorders than low-potency Antipsychotics, whereas the low-potency drugs were more likely to cause dizziness, drowsiness and sedation, a dry mouth, nausea and sometimes even vomiting. The number of included studies was low and the quality of evidence provided was moderate. Therefore, further good quality studies would be needed to draw firm conclusions about the relative effectiveness of fluphenazine compared to low-potency Antipsychotics. Important information on service use, going into hospital again (rehospitalisation), costs and quality of life was missing and not reported.
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The Cochrane Library - Haloperidol versus low‐potency First‐Generation Antipsychotic drugs for schizophrenia
Cochrane Database of Systematic Reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract:People with schizophrenia often hear voices or see things (hallucinations) and have strange beliefs (delusions). It is a serious, often long lasting, mental illness that can have a severe detrimental effect on all aspects of the sufferer's life. Antipsychotic drugs are the main treatment for the symptoms of schizophrenia. Fluphenazine is an older Antipsychotic that is effective in treating the symptoms of schizophrenia. However, most Antipsychotics have side effects and when compared to newer Antipsychotic drugs, fluphenazine is thought to be more likely to cause serious movement disorders such as involuntary shaking, tremors, muscle stiffness and the inability to sit still. Fluphenazine is also known to lower people’s mood. Prescribing low-strength or low-potency drugs can help reduce side effects but are often seen as less effective in treating symptoms. This review examined the effects of the high-potency Antipsychotic fluphenazine compared with those of low-potency Antipsychotics. A search for randomised trials comparing these types of drugs was carried out in 2010. The review includes seven studies with 1567 participants. Pooled data from two of these trials did not show a clear difference in effectiveness between fluphenazine and low-potency Antipsychotics. However, evidence showed fluphenazine produced more movement disorders than low-potency Antipsychotics, whereas the low-potency drugs were more likely to cause dizziness, drowsiness and sedation, a dry mouth, nausea and sometimes even vomiting. The number of included studies was low and the quality of evidence provided was moderate. Therefore, further good quality studies would be needed to draw firm conclusions about the relative effectiveness of fluphenazine compared to low-potency Antipsychotics. Important information on service use, going into hospital again (rehospitalisation), costs and quality of life was missing and not reported.
Peter B. Jones - One of the best experts on this subject based on the ideXlab platform.
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extrapyramidal motor side effects of First and second Generation Antipsychotic drugs
British Journal of Psychiatry, 2012Co-Authors: Michael J Peluso, Thomas R. E. Barnes, Sha N W Lewis, Peter B. JonesAbstract:Background Second-Generation Antipsychotics have been thought to cause fewer extrapyramidal side-effects (EPS) than First-Generation Antipsychotics, but recent pragmatic trials have indicated equivalence. Aims To determine whether second-Generation Antipsychotics had better outcomes in terms of EPS than First-Generation drugs. Method We conducted an intention-to-treat, secondary analysis of data from an earlier randomised controlled trial ( n = 227). A clinically significant difference was defined as double or half the symptoms in groups prescribed First- v. second-Generation Antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for First-Generation drugs) or less than 0.5 (indicating advantage for the newer drugs). We also examined EPS in terms of symptoms emergent at 12 weeks and 52 weeks, and symptoms that had resolved at these time points. Results At baseline those randomised to the First-Generation Antipsychotic group ( n = 118) had similar EPS to the second-Generation group ( n = 109). Indications of resolved Parkinsonism (OR = 0.5) and akathisia (OR = 0.4) and increased tardive dyskinesia (OR = 2.2) in the second-Generation drug group at 12 weeks were not statistically significant and the effects were not present by 52 weeks. Patients in the second-Generation group were dramatically (30-fold) less likely to be prescribed adjunctive anticholinergic medication, despite equivalence in terms of EPS. Conclusions The expected improvement in EPS profiles for participants randomised to second-Generation drugs was not found; the prognosis over 1 year of those in the First-Generation arm was no worse in these terms. The place of careful prescription of First-Generation drugs in contemporary practice remains to be defined, potentially improving clinical effectiveness and avoiding life-shortening metabolic disturbances in some patients currently treated with the narrow range of second-Generation Antipsychotics used in routine practice. This has educational implications because a Generation of psychiatrists now has little or no experience with First-Generation Antipsychotic prescription.
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randomized controlled trial of the effect on quality of life of second vs First Generation Antipsychotic drugs in schizophrenia cost utility of the latest Antipsychotic drugs in schizophrenia study cutlass 1
Archives of General Psychiatry, 2006Co-Authors: Peter B. Jones, Linda Davies, Thomas R. E. Barnes, R.m. Murray, Graham Dunn, Karen P Hayhurst, A. Markwick, Helen Lloyd, Shôn LewisAbstract:CONTEXT: Second-Generation (atypical) Antipsychotics (SGAs) are more expensive than First-Generation (typical) Antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms. OBJECTIVE: To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs. DESIGN: A noncommercially funded, pragmatic, multisite, randomized controlled trial of Antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis. SETTING: Fourteen community psychiatric services in the English National Health Service. PARTICIPANTS: Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects. INTERVENTIONS: Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist. MAIN OUTCOME MEASURES: Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care. RESULTS: The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar. CONCLUSIONS: In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.
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randomized controlled trial of effect of prescription of clozapine versus other second Generation Antipsychotic drugs in resistant schizophrenia
Schizophrenia Bulletin, 2005Co-Authors: Shôn Lewis, Linda Davies, Thomas R. E. Barnes, R.m. Murray, Graham Dunn, Karen P Hayhurst, A. Markwick, Helen Lloyd, Peter B. JonesAbstract:There is good evidence that clozapine is more efficacious than First-Generation Antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-Generation Antipsychotic (SGA) drugs. A noncommercially funded, pragmatic, open, multisite, randomized controlled trial was conducted in the United Kingdom National Health Service (NHS). Participants were 136 people aged 18-65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous Antipsychotic drugs. Participants were randomly allocated to clozapine or to one of the class of other SGA drugs (risperidone, olanzapine, quetiapine, amisulpride) as selected by the managing clinician. Outcomes were assessed blind to treatment allocation. One-year assessments were carried out in 87% of the sample. The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score (3.63 points; CI: 0.46-7.71; p = .08) but did show an advantage in Positive and Negative Syndrome Scale (PANSS) total score that was statistically significant (-4.93 points; CI: -8.82 to -1.05; p = .013) during follow-up. Clozapine showed a trend toward having fewer total extrapyramidal side effects. At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs. In conclusion, in people with schizophrenia with poor treatment response to 2 or more Antipsychotic drugs, there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year.
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Randomised controlled trial of effect on quality of life of prescription of second Generation (atypical) versus First Generation Antipsychotic drugs in schizophrenia [Abstract]. 20th International Congress on Schizophrenia Research, Savannah, Georgia
Schizophrenia Bulletin, 2005Co-Authors: Peter B. Jones, Linda Davies, Thomas R. E. Barnes, R.m. Murray, Graham Dunn, Karen P Hayhurst, A. Markwick, Helen Lloyd, Shôn LewisAbstract:Objectives: To compare the class of conventional, First Generation Antipsychotic drugs (FGA) with the atypical, second Generation drugs (SGA) other than Clozapine, in people with schizophrenia needing a change in treatment because of poor response or side effects. We hypothesized that SGA drugs would be associated with improvement in health-related quality of life. Design: A five-centre,RCT with three, blinded follow-up assessments over one year. The trial was conducted in general adult mental health settings in 14 NHS Trusts in Greater Manchester, Nottingham, Cambridge and London.Participants: 227 participants age 18-65 with schizophrenia and related disorders. Intervention: Random allocation to prescription from the class of SGA drugs, other than Clozapine, available at the time of the trial (Amisulpride, Olanzapine, Quetiapine, Risperidone) or to an FGA drug; choice of drug from within the randomised class was made by the managing clinician. Main Outcome Measures: The primary outcome was the Quality of Life Scale (QLS). Secondary outcomes included symptoms (PANSS), side effects and participant satisfaction. Results: The primary hypothesis of a five point improvement in QLS over the year following commencement of SGA compared with FGA drugs was excluded by an intention to treat analysis. Participants in the FGA arm showed a trend towardsgreater improvements in QLS and symptoms scores, suggesting failure to find the predicted advantage for SGA drugs was unlikely to be due to low statistical power (75%). Participants reported no clear preference for either class of drug. Conclusion: In people with schizophrenia whose medication is being changed because of intolerance or broadly-defined ineffectiveness, there is no disadvantage over one year in terms of quality of life, symptoms or associated costs of care in commencing conventional FGA drugs rather than atypical SGA drugs. This result is not accounted for by inadequate power or by patterns of drug discontinuation.
John M. Davis - One of the best experts on this subject based on the ideXlab platform.
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second Generation versus First Generation Antipsychotic drugs for schizophrenia a meta analysis
The Lancet, 2009Co-Authors: Stefan Leucht, Caroline Corves, Dieter Arbter, Rolf R. Engel, Chunbo Li, John M. DavisAbstract:Summary Background Because of the debate about whether second-Generation Antipsychotic drugs are better than First-Generation Antipsychotic drugs, we did a meta-analysis of randomised controlled trials to compare the effects of these two types of drugs in patients with schizophrenia. Methods We compared nine second-Generation Antipsychotic drugs with First-Generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. Findings We included 150 double-blind, mostly short-term, studies, with 21 533 participants. We excluded open studies because they systematically favoured second-Generation drugs. Four of these drugs were better than First-Generation Antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride −0·31 [95% CI −0·44 to −0·19, p Interpretation Second-Generation Antipsychotic drugs differ in many properties and are not a homogeneous class. This meta-analysis provides data for individualised treatment based on efficacy, side-effects, and cost. Funding National Institute of Mental Health.
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Second-Generation versus First-Generation Antipsychotic drugs for schizophrenia : a meta-analysis. Commentary
The Lancet, 2009Co-Authors: Peter Tyrer, Timothy J. Kendall, Stefan Leucht, Caroline Corves, Dieter Arbter, Rolf R. Engel, John M. DavisAbstract:Background Because of the debate about whether second-Generation Antipsychotic drugs are better than First-Generation Antipsychotic drugs, we did a meta-analysis of randomised controlled trials to compare the effects of these two types of drugs in patients with schizophrenia. Methods We compared nine second-Generation Antipsychotic drugs with First-Generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. Findings We included 150 double-blind, mostly short-term, studies, with 21533 participants. We excluded open studies because they systematically favoured second-Generation drugs. Four of these drugs were better than First-Generation Antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride -0.31 [95% CI -0.44 to -0.19, p
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second Generation versus First Generation Antipsychotic drugs for schizophrenia a meta analysis commentary
The Lancet, 2009Co-Authors: Peter Tyrer, Timothy J. Kendall, Stefan Leucht, Caroline Corves, Dieter Arbter, Rolf R. Engel, John M. DavisAbstract:Background Because of the debate about whether second-Generation Antipsychotic drugs are better than First-Generation Antipsychotic drugs, we did a meta-analysis of randomised controlled trials to compare the effects of these two types of drugs in patients with schizophrenia. Methods We compared nine second-Generation Antipsychotic drugs with First-Generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. Findings We included 150 double-blind, mostly short-term, studies, with 21533 participants. We excluded open studies because they systematically favoured second-Generation drugs. Four of these drugs were better than First-Generation Antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride -0.31 [95% CI -0.44 to -0.19, p<0.0001], clozapine -0.52 [-0.75 to -0.29, p<0.0001], olanzapine -0.28 [-0.38 to -0.18, p<0.0001], and risperidone -0.13 [-0.22 to -0.05, p=0.002]). The other second-Generation drugs were not more efficacious than the First-Generation drugs, even for negative symptoms. Therefore efficacy on negative symptoms cannot be a core component of atypicality. Second-Generation Antipsychotic drugs induced fewer extrapyramidal side-effects than did haloperidol (even at low doses). Only a few have been shown to induce fewer extrapyramidal side-effects than low-potency First-Generation Antipsychotic drugs. With the exception of aripiprazole and ziprasidone, second-Generation Antipsychotic drugs induced more weight gain, in various degrees, than did haloperidol but not than low-potency First-Generation drugs. The second-Generation drugs also differed in their sedating properties. We did not note any consistent effects of moderator variables, such as industry sponsorship, comparator dose, or prophylactic antiparkinsonian medication. Interpretation Second-Generation Antipsychotic drugs differ in many properties and are not a homogeneous class. This meta-analysis provides data for individualised treatment based on efficacy, side-effects, and cost.
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Issues that May Determine the Outcome of Antipsychotic Trials: Industry Sponsorship and Extrapyramidal Side Effect
Neuropsychopharmacology, 2008Co-Authors: John M. Davis, Nancy Chen, Ira D GlickAbstract:This study presents a meta-analysis of the influence of several potentially biasing factors (eg industry support, extrapyramidal side effects) on efficacy of studies comparing second-Generation Antipsychotic (SGA) with First-Generation Antipsychotic (FGA) medications. We used the dataset from our previously published meta-analysis of 124 randomized controlled trials (RCTs) comparing SGAs with FGAs, to evaluate whether certain possible biases could influence the actual outcome on the total score of the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impressions (CGI) scores. Industry sponsorship was determined by contact with authors or publication statement. We calculated whether (1) industry sponsorship, (2) study quality, (3) extrapyramidal symptoms (EPS) properties, or (4) prophylactic antiparkinsonian medications influenced SGA vs FGA efficacy for each drug and averaged overall by two Hedges and Olkin-based meta-analyses. The analysis found that none of the factors was significantly associated with a particular outcome. While industry-sponsored articles may conclude their medication to be more favorable than that of a competitor in an RCT, we found that the observed efficacy was not influenced by sponsorship. Many attribute the finding that SGAs appears to be more efficacious than FGAs to be a result of EPS-decreasing efficacy (or its measurement). We were unable to confirm that the drug's EPS properties or antiparkinsonian management altered actual efficacy.
Magdolna Tardy - One of the best experts on this subject based on the ideXlab platform.
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The Cochrane Library - Haloperidol versus First-Generation Antipsychotics for the treatment of schizophrenia and other psychotic disorders.
Cochrane Database of Systematic Reviews, 2015Co-Authors: Markus Dold, Magdolna Tardy, Myrto Samara, Stefan LeuchtAbstract: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.
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Perphenazine versus low-potency First-Generation Antipsychotic drugs for schizophrenia.
The Cochrane database of systematic reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract: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. To review the effects of high-potency, First-Generation perphenazine compared with low-potency, First-Generation Antipsychotic drugs for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (October 2010). We included all randomised controlled trials (RCTs) comparing perphenazine with First-Generation, low-potency Antipsychotic drugs for people with schizophrenia or schizophrenia-like psychoses. 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. 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. 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.
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Flupenthixol versus low-potency First-Generation Antipsychotic drugs for schizophrenia.
The Cochrane database of systematic reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Markus Dold, Stefan LeuchtAbstract:Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between Antipsychotic drugs, however, low-potency Antipsychotic drugs are sometimes perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects. To review the effects in clinical response of flupenthixol and low-potency Antipsychotics for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (July 2010). Randomised controlled trials that compared flupenthixol with First-Generation low-potency Antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For continuous data, we calculated mean differences (MD) based on a random-effects model. The review currently includes one randomised trial from mainland China with 153 participants that lasted two months and compared flupenthixol with chlorpromazine. The exact methods of sequence Generation and allocation concealment were not reported, and medication was provided in an open manner. There were no data on the outcomes that we had a priori selected for a 'Summary of findings' table.There was no significant difference between flupenthixol and chlorpromazine in the participants' general mental state at endpoint as measured by the Brief Psychiatric Rating Scale (BPRS) total score (1 randomised controlled trial (RCT), n = 153, MD 2.20 95% confidence interval (CI) -1.25 to 5.65). Chlorpromazine was associated with significantly less dizziness (1 RCT, n = 153, MD 0.12 95% CI 0.01 to 0.23); dystonia (1 RCT, n = 153, MD 0.29 95% CI 0.13 to 0.45); unsteady gait (1 RCT, n = 153, MD 0.46 95% CI 0.28 to 0.64); reduced facial expression (1 RCT, n = 153, MD 0.27 95% CI 0.09 to 0.45); restlessness (1 RCT, n = 153, MD 0.69 95% CI 0.45 to 0.93); rigidity (elbow) (1 RCT, n = 153, MD 0.48 95% CI 0.28 to 0.68); and tremor (1 RCT, n = 153, MD 0.56 95% CI 0.34 to 0.78). Chlorpromazine produced more dryness of mouth than flupenthixol (1 RCT, n = 153, MD -0.14 95% CI -0.25 to -0.03). The evidence base of flupenthixol versus low-potency First-Generation Antipsychotics is currently restricted to one randomised comparison with chlorpromazine. The few reported data do not suggest a difference in efficacy, but flupenthixol appeared to produce more movement disorders and dizziness, while chlorpromazine was associated with the anticholinergic side effect - dryness of mouth. More trials are needed to make conclusions about the relative effects of flupenthixol and low-potency Antipsychotics.
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Fluphenazine versus low-potency First-Generation Antipsychotic drugs for schizophrenia.
The Cochrane database of systematic reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract:Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between any other Antipsychotic compounds, however, low-potency Antipsychotic drugs are often perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects. This review examined the effects of the high-potency Antipsychotic fluphenazine compared to those of low-potency Antipsychotics. To review the effects of fluphenazine and low-potency Antipsychotics for people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (November 2010). We included all randomised controlled trials (RCTs) comparing fluphenazine with First-Generation low-potency Antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. The review currently includes seven randomised trials and 1567 participants that compared fluphenazine with low-potency Antipsychotic drugs. The size of the included studies was between 40 and 438 participants. Overall, sequence Generation, allocation procedures and blinding were poorly reported. Fluphenazine was not significantly different from low-potency Antipsychotic drugs in terms of response to treatment (fluphenazine 55%, low-potency drug 55%, 2 RCTs, n = 105, RR 1.06 CI 0.75 to 1.50, moderate quality evidence). There was also no significant difference in acceptability of treatment with equivocal numbers of participants leaving the studies early due to any reason (fluphenazine 36%, low-potency Antipsychotics 36%, 6 RCTs, n = 1532, RR 1.00 CI 0.88 to 1.14, moderate quality evidence). There was no significant difference between fluphenazine and low-potency Antipsychotics for numbers experiencing at least one adverse effect (fluphenazine 70%, low-potency Antipsychotics 88%, 1 RCT, n = 65, RR 0.79 CI 0.58 to 1.07, moderate quality evidence). However, at least one movement disorder occurred significantly more frequently in the fluphenazine group (fluphenazine 15%, low-potency Antipsychotics 10%, 3 RCTs, n = 971, RR 2.11 CI 1.41 to 3.15, low quality of evidence). In contrast, low-potency Antipsychotics produced significantly more sedation (fluphenazine 20%, low-potency Antipsychotics 64%, 1 RCT, n = 65, RR 0.31 CI 0.13 to 0.77, high quality evidence). No data were available for the outcomes of death and quality of life. The results of the primary outcome were robust in a number of subgroup and sensitivity analyses.Adverse effects such as akathisia (fluphenazine 15%, low-potency Antipsychotics 6%, 5 RCTs, n = 1209, RR 2.28 CI 1.58 to 3.28); dystonia (fluphenazine 5%, low-potency Antipsychotics 2%, 4 RCTs, n = 1309, RR 2.66 CI 1.25 to 5.64); loss of associated movement (fluphenazine 20%, low-potency Antipsychotics 2%, 1 RCT, n = 338, RR 11.15 CI 3.95 to 31.47); rigor (fluphenazine 27%, low-potency Antipsychotics 12%, 2 RCTs, n = 403, RR 2.18 CI 1.20 to 3.97); and tremor (fluphenazine 15%, low-potency Antipsychotics 6%, 2 RCTs, n = 403, RR 2.53 CI 1.37 to 4.68) occurred significantly more frequently in the fluphenazine group.For other adverse effects such as dizziness (fluphenazine 8%, low-potency Antipsychotics 17%, 4 RCTs, n = 1051, RR 0.49 CI 0.32 to 0.73); drowsiness (fluphenazine 18%, low-potency Antipsychotics 25%, 3 RCTs, n = 986, RR 0.67 CI 0.53 to 0.86); dry mouth (fluphenazine 11%, low-potency Antipsychotics 18%, 4 RCTs, n = 1051, RR 0.63 CI 0.45 to 0.89); nausea (fluphenazine 4%, low-potency Antipsychotics 15%, 3 RCTs, n = 986, RR 0.25 CI 0.14 to 0.45); and vomiting (fluphenazine 3%, low-potency Antipsychotics 8%, 3 RCTs, n = 986, RR 0.36 CI 0.18 to 0.72) results favoured fluphenazine with significantly more events occurring in the low-potency Antipsychotic group for these outcomes. The results do not show a clear difference in efficacy between fluphenazine and low-potency Antipsychotics. The number of included studies was low and their quality moderate. Therefore, further studies would be needed to draw firm conclusions about the relative effects of fluphenazine and low-potency Antipsychotics.
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haloperidol versus low potency First Generation Antipsychotic drugs for schizophrenia
Cochrane Database of Systematic Reviews, 2014Co-Authors: Magdolna Tardy, Rolf R. Engel, Maximilian Huhn, Stefan LeuchtAbstract:People with schizophrenia often hear voices or see things (hallucinations) and have strange beliefs (delusions). It is a serious, often long lasting, mental illness that can have a severe detrimental effect on all aspects of the sufferer's life. Antipsychotic drugs are the main treatment for the symptoms of schizophrenia. Fluphenazine is an older Antipsychotic that is effective in treating the symptoms of schizophrenia. However, most Antipsychotics have side effects and when compared to newer Antipsychotic drugs, fluphenazine is thought to be more likely to cause serious movement disorders such as involuntary shaking, tremors, muscle stiffness and the inability to sit still. Fluphenazine is also known to lower people’s mood. Prescribing low-strength or low-potency drugs can help reduce side effects but are often seen as less effective in treating symptoms. This review examined the effects of the high-potency Antipsychotic fluphenazine compared with those of low-potency Antipsychotics. A search for randomised trials comparing these types of drugs was carried out in 2010. The review includes seven studies with 1567 participants. Pooled data from two of these trials did not show a clear difference in effectiveness between fluphenazine and low-potency Antipsychotics. However, evidence showed fluphenazine produced more movement disorders than low-potency Antipsychotics, whereas the low-potency drugs were more likely to cause dizziness, drowsiness and sedation, a dry mouth, nausea and sometimes even vomiting. The number of included studies was low and the quality of evidence provided was moderate. Therefore, further good quality studies would be needed to draw firm conclusions about the relative effectiveness of fluphenazine compared to low-potency Antipsychotics. Important information on service use, going into hospital again (rehospitalisation), costs and quality of life was missing and not reported.