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The Cochrane Database of Systematic... Mar 2015Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European countries and Japan.
OBJECTIVES
To examine the clinical effects and safety of perphenazine for those with schizophrenia and schizophrenia-like psychoses.
SEARCH METHODS
We updated our original search using the Cochrane Schizophrenia Group's register (September 2013), references of all included studies and contacted pharmaceutical companies and authors of included studies in order to identify further trials.
SELECTION CRITERIA
We included all randomised controlled trials that compared perphenazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. We excluded trials of depot formulations of perphenazine.
DATA COLLECTION AND ANALYSIS
Two review authors independently inspected citations and, where possible, abstracts. We ordered papers, inspected and quality assessed them. We extracted data, again working independently. If loss to follow-up was greater than 50% we considered results as 'prone to bias'. For dichotomous data, we calculated risk ratios (RR) and for continuous data we calculated mean differences (MD), both with the 95% confidence intervals (CI). We assessed quality of data using the GRADE (Grading of Recommendations Assessment, Development and Evaluationtool) and assessed risk of bias for included studies.
MAIN RESULTS
Thirty-one studies fulfilled the inclusion criteria, with a total of 4662 participants (of which 4522 were receiving the drugs relevant to our comparison) and presented data that could be used for at least one comparison. The trial centres were located in Europe (especially Scandinavia), Japan and Northern America.When comparing perphenazine with placebo, for our primary outcome of clinical response, results favoured perphenazine with significantly more people receiving placebo rated as either 'no better or deterioration' for global state than people receiving perphenazine (1 RCT, n = 61 RR 0.32 CI 0.13 to 0.78, very low quality evidence). More people receiving placebo relapsed, although not a statistically significant number (1 RCT, n = 48, RR 0.14 CI 0.02 to 1.07, very low quality evidence). Death was not reported in the perphenazine versus placebo comparison. Experiences of dystonia were equivocal between groups (1 RCT, n = 48, RR 1.00 CI 0.07 to 15.08, very low quality evidence); other outcomes not reported in this comparison include serious adverse events, economic outcomes, and service use and hospitalisation.For the comparison of perphenazine versus any other antipsychotic drugs, no real differences in effect between the drugs were found. There was no significant difference between groups for those considered 'no better or deterioration' (17 RCTs, n = 1879, RR 1.04 CI 0.91 to 1.17, very low quality evidence). For mental state outcome of 'no effect' of the study drug, there was again no significant difference between groups (4 RCTs, n = 383, RR 1.24 CI 0.61 to 2.52, very low quality evidence). Death was not reported in any of the included studies. There was no significant difference in rates of dystonia with perphenazine versus any other antipsychotic drugs (4 RCTs, n = 416, RR 1.36 CI 0.23 to 8.16, very low quality evidence), nor was there a significant difference between groups for serious adverse events (2 RCTs, n = 1760, RR 0.98 CI 0.68 to 1.41, very low quality evidence).
AUTHORS' CONCLUSIONS
Although perphenazine has been used in randomised trials for more than 50 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. All data for the main outcomes in this review were of very low quality evidence. At best we can say that perphenazine showed similar effects and adverse events as several of the other antipsychotic drugs. Since perphenazine is a relatively inexpensive and frequently used compound, further trials are justified to clarify the properties of this classical antipsychotic drug.
Topics: Antipsychotic Agents; Humans; Mental Disorders; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 25749632
DOI: 10.1002/14651858.CD003443.pub3 -
Journal of B.U.ON. : Official Journal... 2020In the effort to improve treatment effectiveness in glioblastoma, this short note reviewed collected data on the pathophysiology of glioblastoma with particular... (Review)
Review
In the effort to improve treatment effectiveness in glioblastoma, this short note reviewed collected data on the pathophysiology of glioblastoma with particular reference to intersections with the pharmacology of perphenazine. That study identified five areas of potentially beneficial intersection. Data showed seemingly 5 independent perphenazine attributes of benefit to glioblastoma treatment - i) blocking dopamine receptor 2, ii) reducing centrifugal migration of subventricular zone cells by blocking dopamine receptor 3, iii) blocking serotonin receptor 7, iv) activation of protein phosphatase 2, and v) nausea reduction. Perphenazine is fully compatible with current chemoirradiation protocols and with the commonly used ancillary medicines used in clinical practice during the course of glioblastoma. All these attributes argue for a trial of perphenazine's addition to current standard treatment with temozolomide and irradiation. The subventricular zone seeds the brain with mutated cells that become recurrent glioblastoma after centrifugal migration. The current paper shows how perphenazine might reduce that contribution. Perphenazine is an old, generic, cheap, phenothiazine antipsychotic drug that has been in continuous clinical use worldwide since the 1950's. Clinical experience and research data over these decades have shown perphenazine to be well-tolerated in psychiatric populations, in normals, and in non-psychiatric, medically ill populations for whom perphenazine is used to reduce nausea. For now (Summer, 2020) the nature of glioblastoma requires a polypharmacy approach until/unless a core feature and means to address it can be identified in the future. Conclusions: Perphenazine possesses a remarkable constellation of attributes that recommend its use in GB treatment.
Topics: Dopamine Antagonists; Glioblastoma; Humans; Perphenazine
PubMed: 33099901
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2005Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European countries and Japan.
OBJECTIVES
To examine the clinical effects and safety of perphenazine for those with schizophrenia and schizophrenia-like psychoses.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's register (June 2001), references of all included studies and contacted pharmaceutical companies and authors of included studies in order to identify further trials.
SELECTION CRITERIA
We included all randomised controlled trials that compared perphenazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. We excluded trials of depot formulations of perphenazine.
DATA COLLECTION AND ANALYSIS
Two reviewers independently inspected citations and, where possible, abstracts. We ordered papers, inspected and quality assessed them. We extracted data, again working independently. If loss to follow up was greater than 50% we considered results as 'prone to bias'. For dichotomous data we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD).
MAIN RESULTS
The review currently includes 25 studies with 2478 patients, 2285 of whom had been randomised to interventions that were relevant for the review such as perphenazine, other antipsychotic drugs or placebo. The trials were carried out between 1961 and 1993. All but one trial were short term with a duration of between ten days and 12 weeks. Descriptions of allocation and blinding were usually incomplete. Six studies (n=300) compared perphenazine with placebo. Perphenazine was associated with fewer participants leaving the trials early due to relapse or worsening of symptoms (n=84, RR 0.1 CI 0.03 - 0.4, NNT 2 CI 1 to 20). Twenty studies compared perphenazine (n=738) with other antipsychotics (n=1278). Perphenazine seemed as effective as other antipsychotics ('global state unimproved or worse' n=1327, RR 1.0 CI 0.9 to 1.2). We found no clear differences in terms of specific aspects of efficacy, behaviour or tolerability. However, interpretation of findings of the review was limited by poor reporting and the use of 24 different comparator antipsychotics in the 20 trials.
AUTHORS' CONCLUSIONS
Although perphenazine has been randomised for more than 40 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. At best we can say that perphenazine showed similar effects and adverse events as several of the other pooled antipsychotic drugs. Since perphenazine is a relatively inexpensive and frequently used compound, further trials are justified to clarify the properties of this classical antipsychotic drug.
Topics: Antipsychotic Agents; Humans; Mental Disorders; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 15674907
DOI: 10.1002/14651858.CD003443.pub2 -
The Cochrane Database of Systematic... Oct 2014Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between the various first-generation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between the various first-generation antipsychotics, however, low-potency first-generation antipsychotic drugs are sometimes perceived as less efficacious than high-potency first-generation compounds by clinicians, and they also seem to differ in their side effects.
OBJECTIVES
To review the effects of high-potency, first-generation perphenazine compared with low-potency, first-generation antipsychotic drugs for people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (October 2010).
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing perphenazine with first-generation, low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis and using a random-effects model.
MAIN RESULTS
The review currently includes four relevant randomised trials with 365 participants. The size of the included studies was between 42 and 158 participants with a study length between one and four months. Overall, the methods of sequence generation and allocation concealment were poorly reported. Most studies were rated as low risk of bias in terms of blinding. Overall, attrition bias in the studies was high.The effects of perphenazine and low-potency antipsychotic drugs seemed to be similar in terms of the primary outcome - response to treatment (perphenazine 58%, low-potency antipsychotics 59%, 2 RCTs, n = 138, RR 0.97 CI 0.74 to 1.26 - moderate quality of evidence). There was also no clear evidence of a difference in acceptability of treatment with the number of participants leaving the studies early due to any reason, however results were imprecise (perphenazine 30%, low-potency antipsychotics 28%, 3 RCTs, n = 323, RR 0.78 CI 0.35 to 1.76, very low quality of evidence).There were low numbers of studies available for the outcomes experiencing at least one adverse effect (perphenazine 33%, low-potency antipsychotics 47%, 2 RCTs, n = 165, RR 0.83 CI 0.36 to 1.95, low quality evidence) and experiencing at least one movement disorder (perphenazine 22%, low-potency first-generation antipsychotics 0%, 1 RCT, n = 69, RR 15.62 CI 0.94 to 260.49, low quality evidence), and the confidence intervals for the estimated effects did not exclude important differences. Akathisia was more frequent in the perphenazine group (perphenazine 25%, low-potency antipsychotics 22%, 2 RCTs, n = 227, RR 9.45 CI 1.69 to 52.88), whereas severe toxicity was less so (perphenazine 42%, low-potency antipsychotics 69%, 1 RCT, n = 96, RR 0.61 CI 0.41 to 0.89).There were three deaths in the low-potency group by four months but the difference between groups was not significant (perphenazine 0%, low-potency antipsychotics 2%, 1 RCT, n = 96, RR 0.14 CI 0.01 to 2.69, moderate quality evidence). No data were available for our prespecified outcomes of interest sedation or quality of life. Data were not available for other outcomes such as relapse, service use, costs and satisfaction with care.The event rates reported quote simple aggregates and are not based on the RRs.
AUTHORS' CONCLUSIONS
The results do not show a superiority in efficacy of high-potency perphenazine compared with low-potency first-generation antipsychotics. There is some evidence that perphenazine is more likely to cause akathisia and less likely to cause severe toxicity, but most adverse effect results were equivocal. The number of studies as well as the quality of studies is low, with quality of evidence for the main outcomes ranging from moderate to very low, so more randomised evidence would be needed for conclusions to be made.
Topics: Adult; Antipsychotic Agents; Humans; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 25290157
DOI: 10.1002/14651858.CD009369.pub2 -
The Cochrane Database of Systematic... 2000Anti-psychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the... (Review)
Review
BACKGROUND
Anti-psychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain.
OBJECTIVES
To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes.
SEARCH STRATEGY
Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), the Cochrane Schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) were searched. References of all identified trials were also inspected for more studies and industry contacted.
SELECTION CRITERIA
Randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral anti-psychotics or other depot preparations were compared.
DATA COLLECTION AND ANALYSIS
Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat.
MAIN RESULTS
One study of six months duration, compared perphenazine enanthate to clopenthixol decanoate. There was no differences between the two for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group required anticholinergic drugs than those allocated to clopenthixol decanoate (OR 3.6 CI 1.2-10, NNT 10). A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (OR 0.2 CI 0.06-0.7) than those allocated the decanoate ester of the same drug (NNT 4.0) and required more anticholinergic drugs (OR 0.2 CI 0.08-0.7, NNT 3.7).
REVIEWER'S CONCLUSIONS
Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the two trials with useful data is 236. Neither study observes the effect of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Humans; Perphenazine; Schizophrenia
PubMed: 10796445
DOI: 10.1002/14651858.CD001717 -
The Cochrane Database of Systematic... Jul 2005Antipsychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the... (Review)
Review
BACKGROUND
Antipsychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain.
OBJECTIVES
To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes.
SEARCH STRATEGY
We updated previous searches of the Cochrane Schizophrenia Group Register (June 1998), Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) by searching the Cochrane Schizophrenia Group Register (March 2004). References of all identified trials were also inspected for more studies and industry contacted.
SELECTION CRITERIA
We compared randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral antipsychotics or other depot preparations.
DATA COLLECTION AND ANALYSIS
We reliably selected studies, quality rated them and extracted data. For dichotomous data we estimated the Relative Risk (RR) with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat.
MAIN RESULTS
Only four studies (Ahlfors 1980, Eufe 1979, Knudsen 1985c, Tegeler 1979), randomising a total 313 people could be included in this review and this combined with an overall lack of usable data limits any interpretation of results. Perphenazine enanthate was not significantly any better or worse than other depot antipsychotics in most of the main outcomes such as global state, relapse or leaving the study early. We found some differences favouring the control groups for adverse effects. One study (Ahlfors 1980) of six months' duration (n=172), compared perphenazine enanthate to clopenthixol decanoate. There were no differences between the two groups for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group, however, required anticholinergic drugs than those allocated to clopenthixol decanoate (RR 1.12 CI 1.0 to 1.2, NNT 10).A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (RR 1.36, CI 1.1 to 1.8 NNT 5) than those allocated the decanoate ester of the same drug and required more anticholinergic drugs (RR 1.47 CI 1.1 to 2.0, NNT 4).
AUTHORS' CONCLUSIONS
Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate, a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the four trials with useful data is 313. None of the studies observed the effects of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Humans; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 16034865
DOI: 10.1002/14651858.CD001717.pub2 -
Journal of Clinical Psychopharmacology
Topics: Adolescent; Aggression; Antipsychotic Agents; Disruptive, Impulse Control, and Conduct Disorders; Female; Humans; Nausea; Perphenazine; Psychotic Disorders; Substance Withdrawal Syndrome
PubMed: 34369907
DOI: 10.1097/JCP.0000000000001436 -
DICP : the Annals of Pharmacotherapy Mar 1990A 29-year-old man experienced four episodes of prolonged painful erection while being treated with perphenazine for paranoid schizophrenia. Each episode of priapism...
A 29-year-old man experienced four episodes of prolonged painful erection while being treated with perphenazine for paranoid schizophrenia. Each episode of priapism lasted five hours or longer. On two occasions, aspiration of blood from the corpora cavernosa resulted in detumescence; the other episodes were successfully managed with operative shunting of blood from the congested cavernosa. Perphenazine was discontinued after the fourth episode of priapism and antipsychotic treatment with thiothixene was subsequently initiated. During 16 months of follow-up, the patient has reported normal erections without repeat episodes of priapism.
Topics: Adult; Humans; Male; Perphenazine; Priapism; Schizophrenia, Paranoid
PubMed: 2316231
DOI: 10.1177/106002809002400306 -
Anesthesia and Analgesia Feb 2021
Topics: Antiemetics; Humans; Perphenazine; Postoperative Nausea and Vomiting
PubMed: 33449568
DOI: 10.1213/ANE.0000000000005279 -
Journal of Neuro-oncology Jan 2014We present here a potential new treatment adjunct for glioblastoma. Building on murine studies, a series of papers appeared recently showing that therapeutic irradiation... (Review)
Review
We present here a potential new treatment adjunct for glioblastoma. Building on murine studies, a series of papers appeared recently showing that therapeutic irradiation of the ipsilateral subventricular zone (SVZ) retards growth of more peripherally growing cortical glioblastomas in humans, suggesting a tumor trophic function for the SVZ. Further studies showed that SVZ cells migrate out towards a peripheral glioblastoma. Dopamine signaling through D3 subtype receptor indirectly drives this centrifugal migration in humans. Since psychiatry has several drugs with good D3 blocking attributes, such as fluphenazine, or perphenazine, we suggest that adding one of these D3 blocking drugs to current standard treatment of resection followed by temozolomide and irradiation might prolong survival by depriving glioblastoma of the trophic functions previously subserved by dopaminergic signaling on SVZ cells.
Topics: Brain Neoplasms; Cerebral Ventricles; Dopamine Antagonists; Glioblastoma; Humans; Neoplastic Stem Cells; Perphenazine
PubMed: 24242756
DOI: 10.1007/s11060-013-1308-y