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Profiles of Drug Substances,... 2012
Review
Topics: Animals; Antipsychotic Agents; Drug Stability; Humans; Pimozide; Spectrum Analysis
PubMed: 22469321
DOI: 10.1016/B978-0-12-397220-0.00007-6 -
Clinical and Experimental Pharmacology... Feb 2019Over the past years, studies have described that users of antipsychotics are less likely to develop cancer than the population in general due to cytotoxic properties of... (Review)
Review
Over the past years, studies have described that users of antipsychotics are less likely to develop cancer than the population in general due to cytotoxic properties of this class of drugs on cancer cells. For this reason, Pimozide has been widely studied as a potential anticancer treatment, and satisfactory results in melanoma, central nervous system tumours, osteosarcoma, neuroblastoma, myeloproliferative neoplasms, breast, lung, prostate, ovarian, colorectal, pancreatic, and hepatocellular carcinoma have been showed. Moreover, advantages as clinical use approved by the Food and Drug Administration (FDA), high clinical safety, low side effects, and reasonable price have stimulated the treatment with Pimozide instead of other agents. The action mechanism remains unclear, but three vias associated to cancer stem cell (CSC) hypothesis show that Pimozide: (a) blocks CSC features, as epithelial-to-mesenchymal transition (EMT), through inhibition of Wnt-β/catenin signalling; (b) acts as an inhibitor of signal transducer and activator of transcription (STAT-3 and 5), pathway which is activated and up-regulated in CSCs; (c) inhibits ubiquitine specific protease (USP1) and WD repeat-containing protein 48 (WDR48), that are proteins responsible to inhibit the differentiation and to maintain the cell in an undifferentiated state. Based on this perspective, the aim of this manuscript is to review the antineoplastic role of Pimozide during tumorigenesis and its potential to revert the process of undifferentiation and proliferation of CSC through different vias.
Topics: Animals; Antineoplastic Agents; Humans; Neoplasms; Neoplastic Stem Cells; Pimozide
PubMed: 30383889
DOI: 10.1111/1440-1681.13049 -
The Cochrane Database of Systematic... Apr 2009Neuroleptic drugs with potent D-2 receptor blocking properties have been the traditional treatment for tics caused by Tourette Syndrome. Pimozide is the most studied of... (Review)
Review
BACKGROUND
Neuroleptic drugs with potent D-2 receptor blocking properties have been the traditional treatment for tics caused by Tourette Syndrome. Pimozide is the most studied of these. Use of these medications is declining because of concerns about side effects, and new atypical neuroleptics are now available. The true benefit and risks associated with pimozide compared to other drugs is not known.
OBJECTIVES
To evaluate the efficacy and harms of pimozide in comparison to placebo or other medications in the treatment of tics in Tourette Syndrome.
SEARCH STRATEGY
We cross-referenced pimozide and its proprietary names with Tourette Syndrome and its derivations, as MeSH headings and as text words, and searched the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4), MEDLINE (1950-April 2007), and EMBASE (1980-April 2007). Reference lists of relevant articles were reviewed for additional trials.
SELECTION CRITERIA
All randomized, controlled, double blind studies comparing pimozide to placebo or other medications for the treatment of tics in Tourette Syndrome were considered for inclusion in this review. Both parallel group and crossover studies of children or adults, at any dose and for any duration, were included.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by two authors onto standardized forms and disagreements were resolved by discussion.
MAIN RESULTS
Six randomized controlled trials were included (total 162 participants, age range 7 to 53 years). Pimozide was compared with: placebo and haloperidol (two trials), placebo (one trial), haloperidol (one trial), and risperidone (two trials). Methodological quality was rated 'fair' for all studies. Studies used different outcome measurement scales for assessing tic severity and adverse effects. Significant clinical heterogeneity made meta-analysis inappropriate. Pimozide was superior to placebo in three studies, though it caused more side effects than placebo in one of these. Pimozide was inferior to haloperidol in one of three studies (the other two showed no significant difference between the drugs), which also showed significantly fewer side effects associated with pimozide. No significant differences between pimozide and risperidone were detected.
AUTHORS' CONCLUSIONS
Pimozide is an effective treatment for tics in Tourette Syndrome, though the number of trials comparing its effect to placebo and other drugs is limited. Trials of longer duration (minimum six months) are needed to investigate the longer-term effects of pimozide compared to atypical neuroleptics. Future trials should use the Yale Global Tic Severity Scale to assess the main outcome measure, and quantify adverse events with the Extrapyramidal Symptoms Rating Scale.
Topics: Anti-Dyskinesia Agents; Haloperidol; Humans; Pimozide; Randomized Controlled Trials as Topic; Risperidone; Tics; Tourette Syndrome
PubMed: 19370666
DOI: 10.1002/14651858.CD006996.pub2 -
Drugs 1976Pimozide 1-(1-[4,4-bis(4-fluorophenyl)butyl]-4-peperidinyl)-2-benzimidazolone, is the first of a new series of psychotropic drugs, the kiphenylbutylpiperidines. It is... (Review)
Review
Pimozide 1-(1-[4,4-bis(4-fluorophenyl)butyl]-4-peperidinyl)-2-benzimidazolone, is the first of a new series of psychotropic drugs, the kiphenylbutylpiperidines. It is advocated for once-daily use as maintenance therapy in chronic schizophrenia and for the treatment of psychic and functional disorders induced by personality traits. Published data suggest that in chronic schizophrenia, pimozide 4 to 6mg daily is indistinguishable from maintenance doses of chlorpromazine, fluphenazine, flupenthixol, perphenazine, or thioidazine. Patient groups have usually been to small to allow statistically significant differences to be apparent, but in some trials pimozide was significantly superior to trifluoperzine and to haloperidol. On present evidence, pimozide has no place in the hyperactive, aggressive type of patient or in treating the acute phase of schizophrenia, probably because of its relative lack of sedative properties compared with many antipsychotic drugs. The incidence and severity of extrapyramidal reactions with pimozide are low, but suitably designed controlled studies are needed to determine whether its use leads to a reduction in the requirement for antiparkinsonian medication. In anxious patients, pimozide seems to offer no advantages over currently available anxiolytic agents, either in terms of efficacy or incidence of side-effects. Claims for a specific effect against anxiety associated with psychosis or disturbed personality traits remain unproven.
Topics: Adult; Animals; Anxiety; Behavior, Animal; Child; Dogs; Drug Interactions; Haplorhini; Humans; Lipodystrophy; Mental Disorders; Mice; Movement Disorders; Pimozide; Rabbits; Rats; Schizophrenia; Teratogens
PubMed: 824116
DOI: 10.2165/00003495-197612010-00001 -
The Cochrane Database of Systematic... Nov 2013Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been associated with cardiotoxicity and sudden unexplained death. Electrocardiogram monitoring is now required before and during use.
OBJECTIVES
To review the effects of pimozide for people with schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.A secondary objective was to examine the effects of pimozide for people with delusional disorder.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Register (28 January 2013).
SELECTION CRITERIA
We sought all relevant randomised clinical trials (RCTs) comparing pimozide with other treatments.
DATA COLLECTION AND ANALYSIS
Working independently, we inspected citations, ordered papers and then re-inspected and assessed the quality of the studies and of extracted data. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and mean differences (MDs) for continuous data. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence.
MAIN RESULTS
We included 32 studies in total: Among the five studies that compared pimozide versus placebo, only one study provided data for global state relapse, for which no difference between groups was noted at medium term (1 RCT n = 20, RR 0.22 CI 0.03 to 1.78, very low quality of evidence). None of the five studies provided data for no improvement or first-rank symptoms in mental state. Data for extrapyramidal symptoms demonstrate no difference between groups for Parkinsonism (rigidity) at short term (1 RCT, n = 19, RR 5.50 CI 0.30 to 101.28, very low quality of evidence) or at medium term (1 RCT n = 25, RR 1.33 CI 0.14 to 12.82, very low quality of evidence), or for Parkinsonism (tremor) at medium term (1 RCT n = 25, RR 1 CI 0.2 to 4.95, very low quality of evidence). No data were reported for quality of life at medium term.Of the 26 studies comparing pimozide versus any antipsychotic, seven studies provided data for global state relapse at medium term, for which no difference was noted (7 RCTs n = 227, RR 0.82 CI 0.57 to 1.17, moderate quality of evidence). Data from one study demonstrated no difference in mental state (no improvement) at medium term (1 RCT n = 23, RR 1.09 CI 0.08 to 15.41, very low quality evidence); another study demonstrated no difference in the presence of first-rank symptoms at medium term (1 RCT n = 44, RR 0.53 CI 0.25 to 1.11, low quality of evidence). Data for extrapyramidal symptoms demonstrate no difference between groups for Parkinsonism (rigidity) at short term (6 RCTs n = 186, RR 1.21 CI 0.71 to 2.05,low quality of evidence) or medium term (5 RCTs n = 219, RR 1.12 CI 0.24 to 5.25,low quality of evidence), or for Parkinsonism (tremor) at medium term (4 RCTs n = 174, RR 1.46 CI 0.68 to 3.11, very low quality of evidence). No data were reported for quality of life at medium term.In the one study that compared pimozide plus any antipsychotic versus the same antipsychotic, significantly fewer relapses were noted in the augmented pimozide group at medium term (1 RCT n = 69, RR 0.28 CI 0.15 to 0.50, low quality evidence). No data were reported for mental state outcomes or for extrapyramidal symptoms (EPS). Data were skewed for quality of life scores, which were not included in the meta-analysis but were presented separately.Two studies compared pimozide plus any antipsychotics versus antipsychotic plus placebo; neither study reported data for outcomes of interest, apart from Parkinsonism at medium term and quality of life using the Specific Level of Functioning scale (SLOF); however, data were skewed.Only one study compared pimozide plus any antipsychotic versus antipsychotics plus antipsychotic; no data were reported for global state and mental state outcomes of interest. Data were provided for Parkinsonism (rigidity and tremor) using the Extrapyramidal Symptom Rating Scale (ESRS); however, these data were skewed.
AUTHORS' CONCLUSIONS
Although shortcomings in the data are evident, enough overall consistency over different outcomes and time scales is present to confirm that pimozide is a drug with efficacy similar to that of other, more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia. No data support or refute its use for those with delusional disorder.
Topics: Antipsychotic Agents; Delusions; Humans; Pimozide; Psychotic Disorders; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia; Schizophrenic Psychology
PubMed: 24194433
DOI: 10.1002/14651858.CD001949.pub3 -
Drug Intelligence & Clinical Pharmacy Jun 1985The orphan drug pimozide was recently approved for marketing in the U.S. for the treatment of Tourette's syndrome (TS). TS is characterized by recurrent, involuntary... (Review)
Review
The orphan drug pimozide was recently approved for marketing in the U.S. for the treatment of Tourette's syndrome (TS). TS is characterized by recurrent, involuntary motor movements and vocal tics, and is believed to be due to neurochemical dysfunction. Pimozide's receptor selectivity differs from that of haloperidol, the standard agent used for TS. Clinical trials with pimozide demonstrate a positive response for many patients, although superiority over haloperidol has not been demonstrated in general. Pimozide causes annoying side effects in a large percentage of patients and may cause severe side effects (e.g., tardive dyskinesia, cardiovascular toxicity) with prolonged use and/or at higher doses. The long half-life of pimozide allows for once-daily dosing. Pimozide should be reserved for treatment of patients with TS who have not responded to haloperidol or who cannot tolerate haloperidol's adverse effects.
Topics: Formularies as Topic; Humans; Pimozide; Tourette Syndrome
PubMed: 3891283
DOI: 10.1177/106002808501900602 -
Dermatology Online Journal Mar 2003Pimozide is widely used in psychiatry for chronic psychoses, schizophrenia, the syndrome of Gilles de la Tourette and to a certain extent, also in dermatology. The only... (Review)
Review
Pimozide is widely used in psychiatry for chronic psychoses, schizophrenia, the syndrome of Gilles de la Tourette and to a certain extent, also in dermatology. The only dermatological indication is for delusions of parasitosis. Though there is a good rationale for using pimozide in this disease, the majority of the studies on pimozide in dermatology are uncontrolled trials and case reports.
Topics: Antipsychotic Agents; Drug Interactions; Pimozide
PubMed: 12639456
DOI: No ID Found -
The Cochrane Database of Systematic... 2000Pimozide was first formulated in the late 1960s and marketed for the care of those with schizophrenia or related psychoses such as delusional disorder. (Review)
Review
BACKGROUND
Pimozide was first formulated in the late 1960s and marketed for the care of those with schizophrenia or related psychoses such as delusional disorder.
OBJECTIVES
To assess the effects of pimozide for people with schizophrenia, non-affective psychotic mental illness and delusional disorder in terms of clinical, social and economic outcomes.
SEARCH STRATEGY
Electronic searches of Biological Abstracts (1982-1995), The Cochrane Schizophrenia Group's Register, EMBASE (1980-1995), Janssen-Cilag UK's register of studies (1999), MEDLINE (1966-1995), PsycLIT (1974-1995), hand-searching the references of all included studies and contacting the manufacturers of the compound.
SELECTION CRITERIA
All randomised trials relating to people with schizophrenia, or similar disorders comparing pimozide to other drug treatments were sought. Studies where randomisation was implied rather than stated were included if they did not change the results. Primary outcomes were clinically significant change in global function, mental state, relapse, hospital admission, death, adverse events and acceptability of treatment.
DATA COLLECTION AND ANALYSIS
Studies were selected, rated and data extracted. For dichotomous data Relative Risks (RR) based on a random effects model with the 95% confidence intervals (CI) were estimated. The number needed to treat statistic (NNT) was calculated where indicated. Analysis was by intention-to-treat.
MAIN RESULTS
This review currently includes 34 studies focusing on those with schizophrenia, none on people with delusional disorder. Few people have been randomised to pimozide versus placebo, but data from three longer term studies does suggest that the active drug prevents relapse (RR 0.59 CI 0.4-0.8, NNT 4 CI 2-13). Pimozide has similar efficacy to that of typical antipsychotic drugs for the outcomes of change in global functioning, mental state, relapse and leaving the study early. People allocated to pimozide did not have a higher mortality than those taking other antipsychotics. Pimozide was more likely to cause parkinsonian tremor (RR 1.6 CI 1.1-2.3, NNH 6 CI 3-44) and lead to a requirement for antiparkinsonian medication more frequently (RR 1.8, CI 1.2-2.6, NNH 3 CI 2-5) than other drugs. It was, however, less likely to cause sedation (RR 0.38 CI 0.2-0.7, NNH 6 CI 4-16).
REVIEWER'S CONCLUSIONS
Although there are shortcomings in the data there is enough overall consistency, over different outcomes and time scales, to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotics such as chlorpromazine for those with schizophrenia. There are no data to support or refute its use for those with delusional disorder.
Topics: Antipsychotic Agents; Humans; Pimozide; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology
PubMed: 10796672
DOI: 10.1002/14651858.CD001949 -
The Cochrane Database of Systematic... Jul 2007Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been associated with cardiotoxicity and sudden unexplained deaths. Electrocardiogram monitoring is now required before and during use.
OBJECTIVES
To assess the clinical effects of pimozide for people with schizophrenia, non-affective psychotic mental illness and delusional disorder.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's Register (July 2005).
SELECTION CRITERIA
We sought all relevant randomised clinical trials comparing pimozide with other treatments.
DATA COLLECTION AND ANALYSIS
Working independently, we inspected citations, ordered papers, and then re-inspected and quality assessed the studies and extracted data. For homogeneous dichotomous data, we calculated the relative risk (RR), 95% confidence interval (CI), and, where appropriate, the number needed to treat (NNT) and the number needed to harm (NNH), on an intention-to-treat basis. We calculated weighted mean differences (WMD) for continuous data. We excluded data if loss to follow-up was greater than 50%.
MAIN RESULTS
We found 35 relevant studies (total n=1348), all including people with schizophrenia but none with delusional disorder. 123 people were randomised to pimozide versus placebo. Data suggest that pimozide prevents relapse (2 RCTs, n=66, RR 0.45 CI 0.2 to 0.9, NNT 4 CI 3 to 22). Compared with typical antipsychotic drugs, pimozide has similar efficacy for outcomes of change in global functioning, mental state, relapse and leaving the study early. People allocated to pimozide did not have a higher mortality than those taking other antipsychotic drugs. Pimozide was more likely than typical antipsychotic drugs to cause tremor in the short-term (6 RCTs, n=192, RR 1.6 CI 1.1 to 2.3, NNH 6 CI 3 to 44) and lead to need for antiparkinsonian medication (4 RCTs, n=124, RR 1.8 CI 1.2 to 2.6, NNH 3 CI 2 to 5) than other drugs. In the medium-term, however, pimozide was less likely to cause sedation (5 RCTs, n=231, RR 0.6 CI 0.5 to 0.9, NNH 6 CI 4 to 16).
AUTHORS' CONCLUSIONS
Although there are shortcomings in the data, there is enough overall consistency over different outcomes and time scales to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia. There are no data to support or refute its use for those with delusional disorder.
Topics: Antipsychotic Agents; Humans; Pimozide; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology
PubMed: 17636692
DOI: 10.1002/14651858.CD001949.pub2 -
The Cochrane Database of Systematic... 2000Pimozide was first formulated in the late 1960s and continues to be marketed for the care of those with schizophrenia or related psychoses such as delusional disorder.... (Review)
Review
BACKGROUND
Pimozide was first formulated in the late 1960s and continues to be marketed for the care of those with schizophrenia or related psychoses such as delusional disorder. Pimozide is generally well tolerated apart from extrapyramidal side effects. It has, however, been associated with cardiotoxicity and sudden unexplained deaths and electrocardiogram monitoring is now required before and during its use.
OBJECTIVES
To assess the effects of pimozide for people with schizophrenia, non-affective psychotic mental illness and delusional disorder in terms of clinical, social and economic outcomes.
SEARCH STRATEGY
Electronic searches of Biological Abstracts (1982-1995), The Cochrane Schizophrenia Group's Register, EMBASE (1980-1995), Janssen-Cilag UK's register of studies (1999), MEDLINE (1966-1995), PsycLIT (1974-1995), hand-searching the references of all included studies and contacting the manufacturers of the compound.
SELECTION CRITERIA
All randomised trials relating to people with schizophrenia, or similar disorders comparing pimozide to other drug treatments were sought. Studies where randomisation was implied rather than stated were included if they did not change the results. Primary outcomes were clinically significant change in global function, mental state, relapse, hospital admission, death, adverse events and acceptability of treatment.
DATA COLLECTION AND ANALYSIS
Studies were selected, rated and data extracted. For dichotomous data Relative Risks (RR) based on a random effects model with 95% confidence intervals (CI) were estimated. The number needed to treat statistic (NNT) was calculated where indicated. Analysis was by intention-to-treat.
MAIN RESULTS
This review currently includes 34 studies focusing on those with schizophrenia, none on people with delusional disorder. Few people have been randomised to pimozide versus placebo. Data from two longer term studies does suggest that the active drug prevents relapse (n=66, RR 0.45 CI 0.24-0.86, NNT 4, CI 3-22) but the confidence interval is wide. Pimozide has similar efficacy to that of typical antipsychotic drugs for the outcomes of change in global functioning, mental state, relapse and leaving the study early. People allocated to pimozide did not have a higher mortality than those taking other antipsychotics. Pimozide was more likely to cause parkinsonian tremor (RR 1.6 CI 1.1-2.3, NNH 6 CI 3-44) and lead to a requirement for antiparkinsonian medication more frequently (RR 1.8, CI 1.2-2.6, NNH 3 CI 2-5) than other drugs. It was, however, less likely to cause sedation (RR 0.38 CI 0.2-0.7, NNH 6 CI 4-16).
REVIEWER'S CONCLUSIONS
Although there are shortcomings in the data there is enough overall consistency, over different outcomes and time scales, to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotics such as chlorpromazine for those with schizophrenia. There are no data to support or refute its use for those with delusional disorder.
Topics: Antipsychotic Agents; Humans; Pimozide; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology
PubMed: 10908518
DOI: 10.1002/14651858.CD001949