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BMJ Open Ophthalmology 2022This review assesses different clinical aspects of the various known drug-induced corneal deposits, based on the corneal layer involved (epithelium, stroma and/or... (Review)
Review
This review assesses different clinical aspects of the various known drug-induced corneal deposits, based on the corneal layer involved (epithelium, stroma and/or endothelium), and based on the drug class. The most well-known condition caused by drug deposits is vortex keratopathy, or corneal verticillata, which is a whorl-like opacity in the corneal epithelium. Vortex keratopathy is commonly caused by certain cationic amphiphilic drugs such as amiodarone, antimalarials, suramin, tamoxifen, chlorpromazine and non-steroidal anti-inflammatory drugs. These deposits usually occur once a certain dose of the drug is reached. Most cases present with mild to moderate symptoms with minimal visual impairment. Most of these deposits resolve automatically, after months to years of drug cessation. Notably, other drug classes can cause deposits in all three layers of the cornea. Chlorpromazine, gold, rifabutin, indomethacin and tyrosine kinase inhibitors can cause stromal deposits, with reduced visual acuity when the anterior stroma is involved. Chlorpromazine and rifabutin can also cause deposits in the endothelial layer of the cornea. Regardless of the type of corneal deposit, local therapies such as topical lubricants or corticosteroids may help improve symptoms. Drug cessation or modification can also be helpful but should be weighed against the systemic risks of the underlying disease.
Topics: Chlorpromazine; Corneal Dystrophies, Hereditary; Corneal Opacity; Humans; Rifabutin; Vision Disorders
PubMed: 35415268
DOI: 10.1136/bmjophth-2021-000943 -
The Cochrane Database of Systematic... Sep 2017The efficacy of chlorpromazine, a benchmark antipsychotic, has not been fully assessed in direct comparison with different individual antipsychotics. Penfluridol is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The efficacy of chlorpromazine, a benchmark antipsychotic, has not been fully assessed in direct comparison with different individual antipsychotics. Penfluridol is another old antipsychotic with a long half-life so one oral dose may last up to one week. This could confer advantage.
OBJECTIVES
To assess the clinical effects of chlorpromazine compared with penfluridol for adults with schizophrenia.
SEARCH METHODS
On 31 March 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitations for inclusion of records in the register.
SELECTION CRITERIA
We included all randomised clinical trials focusing on chlorpromazine versus penfluridol for adults with schizophrenia or related disorders. Outcomes of interest were death, service utilisation, global state, mental state, adverse effects and leaving the study early. We included trials meeting our selection criteria and reporting useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we planned to estimate the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The review includes three studies with a total of 130 participants. Short-term results for hospital admissions showed no clear difference between chlorpromazine and penfluridol (1 RCT, n = 29, RR 0.19, 95% CI 0.01 to 3.60, low-quality evidence). No clear difference in the incidence of akathisia was found at medium term (2 RCTs, n = 85, RR 0.19, 95% CI 0.04 to 1.06, low-quality evidence), and similar numbers of participants - nearly half - from each treatment group left the study early (3 RCTs, n = 130, RR 1.21, 95% CI 0.83 to 1.77, low-quality evidence). The risk of needing additional antiparkinsonian medication was less in the chlorpromazine group (2 RCTs, n = 74, RR 0.70, 95% CI 0.51 to 0.95). No useable data reported clinically important change in global or mental state. No data were reported for relapse. No deaths were reported by the trials.
AUTHORS' CONCLUSIONS
Only three small studies provided data and the quality of reporting and evidence is low. Limited data indicate the efficacy and adverse effects profiles of chlorpromazine and penfluridol are generally similar. Penfluridol, however, may confer advantage by needing to be given only once per week. Firm conclusions are not possible without good-quality trials, and where these treatments are used, such trials are justified.
Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Chlorpromazine; Humans; Length of Stay; Penfluridol; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 28940256
DOI: 10.1002/14651858.CD011831.pub2 -
The Cochrane Database of Systematic... Mar 2017Chlorpromazine, a widely available and inexpensive antipsychotic drug, is considered the benchmark treatment for schizophrenia worldwide. Metiapine, a dibenzothiazepine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chlorpromazine, a widely available and inexpensive antipsychotic drug, is considered the benchmark treatment for schizophrenia worldwide. Metiapine, a dibenzothiazepine derivative, has been reported to have potent antipsychotic characteristics. However, no evidence currently exists on the effectiveness of chlorpromazine in treatment of people with schizophrenia compared to metiapine, a newer antipsychotic.
OBJECTIVES
To compare the effect of chlorpromazine versus metiapine for the treatment of people with schizophrenia SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials in November 2015 and 2016.
SELECTION CRITERIA
All randomised controlled trials (RCTs) focusing on chlorpromazine versus metiapine for adults with schizophrenia. We included trials meeting our selection criteria and reporting useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included three studies randomising 161 people with schizophrenia. Data were available for only two of our seven prestated main outcomes. Clinically important improvement in global state was measured using the Clinical Global Impression (CGI). There was no clear difference between chlorpromazine and metiapine groups (2 RCTs, n = 120, RR 1.11, 95% CI 0.84 to 1.47, very low quality evidence) and numbers of participants with parkinsonism at eight weeks were similar (2 RCTs, n = 70, RR 0.97, 95% CI 0.46 to 2.03, very low quality evidence). There were no useable data available for the other key outcomes of clinically important improvement in mental state, readmission due to relapse, satisfaction with treatment, aggressive or violent behaviour, or cost of care.
AUTHORS' CONCLUSIONS
Chlorpromazine has been the mainstay treatment for schizophrenia for decades, yet available evidence comparing this drug to metiapine fails to provide high-quality trial based data. However, the need to determine whether metiapine is more or less effective than chlorpromazine seems to be lacking in clinical relevance and future research on this comparison seems unlikely.
Topics: Adult; Antipsychotic Agents; Chlorpromazine; Dibenzothiazepines; Humans; Parkinson Disease, Secondary; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 28349512
DOI: 10.1002/14651858.CD011655.pub2 -
The Cochrane Database of Systematic... Apr 2017Schizophrenia is a chronic, disabling and severe mental disorder, characterised by disturbance in perception, thought, language, affect and motor behaviour.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Schizophrenia is a chronic, disabling and severe mental disorder, characterised by disturbance in perception, thought, language, affect and motor behaviour. Chlorpromazine and clotiapine are among antipsychotic drugs used for the treatment of people with schizophrenia.
OBJECTIVES
To determine the clinical effects, safety and cost-effectiveness of chlorpromazine compared with clotiapine for adults with schizophrenia.
SEARCH METHODS
We searched Cochrane Schizophrenia's Trials Register (last update search 16/01/2016), which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the Register.
SELECTION CRITERIA
All randomised clinical trials focusing on chlorpromazine versus clotiapine for schizophrenia. We included trials meeting our selection criteria and reporting useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
We have included four studies, published between 1974 and 2003, randomising 276 people with schizophrenia to receive either chlorpromazine or clotiapine. The studies were poor at concealing allocation of treatment and blinding of outcome assessment. Our main outcomes of interest were clinically important change in global and mental state, specific change in negative symptoms, incidence of movement disorder (dyskinesia), leaving the study early for any reason, and costs. All reported data were short-term (under six months' follow-up).The trials did not report data for the important outcomes of clinically important change in global or mental state, or cost of care. Improvement in mental state was reported using the Positive and Negative Syndrome Scale (PANSS). When chlorpromazine was compared with clotiapine the average improvement scores for mental state using the PANSS total was higher in the clotiapine group (1 RCT, N = 31, MD 11.50 95% CI 9.42 to 13.58, very low-quality evidence). The average change scores on the PANSS negative sub-scale were similar between treatment groups (1 RCT, N = 21, MD -0.97 95% CI -2.76 to 0.82, very low-quality evidence). There was no clear difference in incidence of dyskinesia (1 RCT, N = 68, RR 3.00 95% CI 0.13 to 71.15, very low-quality evidence). Similar numbers of participants left the study early from each treatment group (3 RCTs, N = 158, RR 0.68 95% CI 0.24 to 1.88, very low-quality evidence).
AUTHORS' CONCLUSIONS
Clinically important changes in global and mental state were not reported. Only one trial reported the average change in overall mental state; results favour clotiapine but these limited data are very difficult to trust due to methodological limitations of the study. The comparative effectiveness of chlorpromazine compared to clotiapine on change in global state remains unanswered. Results in this review suggest chlorpromazine and clotiapine cause similar adverse effects, although again, the quality of evidence for this is poor, making firm conclusions difficult.
Topics: Antipsychotic Agents; Chlorpromazine; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Intention to Treat Analysis; Patient Dropouts; Randomized Controlled Trials as Topic; Risk; Schizophrenia
PubMed: 28387925
DOI: 10.1002/14651858.CD011810.pub2 -
The Cochrane Database of Systematic... Oct 2018Schizophrenia is a severe mental disorder with a prevalence of about 1% among the general population. It is listed among the top 10 causes of disability-adjusted life... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Schizophrenia is a severe mental disorder with a prevalence of about 1% among the general population. It is listed among the top 10 causes of disability-adjusted life years (DALYs) worldwide. Antipsychotics are the mainstay treatment. Piperacetazine has been reported to be as clinically effective as chlorpromazine, a well established 'benchmark' antipsychotic, for people with schizophrenia. However, the side effect profiles of these antipsychotics differ and it is important that an evidence base is available comparing the benefits, and potential harms of these two antipsychotics.
OBJECTIVES
To assess the clinical and side effects of chlorpromazine for people with schizophrenia and schizophrenia-like psychoses in comparison with piperacetazine.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (6 June 2015 and 8 October 2018) which is based on regular searches of CINAHL, CENTRAL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO and registries of clinical trials. There are no language, date, document type, or publication status limitations for inclusion of records in the register.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) focusing on chlorpromazine versus piperacetazine for people with schizophrenia, reporting useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We found 12 records referring to six trials. We included five trials, all from the 1970s, randomising 343 participants. We excluded one trial. The overall methodology and data reporting by the trials was poor. Only short-term data were available.Results from the included trials found that, in terms of global state improvement, when rated by a psychiatrist, there was no clear difference between chlorpromazine and piperacetazine (RR 0.90, 95% CI 0.80 to 1.02; participants = 208; studies = 2; very low-quality evidence). One trial reported change scores on the mental state scale Brief Psychiatric Rating Scale (BPRS); no clear difference was observed (MD -0.40, 95% CI -1.41 to 0.61; participants = 182; studies = 1; very low-quality evidence). Chlorpromazine appears no worse or better than piperacetazine regarding adverse effects. In both treatment groups, around 60% of participants experienced some sort of adverse effect (RR 1.00, 95% CI 0.75 to 1.33; participants = 74; studies = 3; very low-quality evidence), with approximately 40% of these participants experiencing some parkinsonism-type movement disorder (RR 0.95, CI 0.61 to 1.49; participants = 106; studies = 3; very low-quality evidence). No clear difference in numbers of participants leaving the study early for any reason was observed (RR 0.50, 95% CI 0.10 to 2.56; participants = 256; studies = 4; very low-quality evidence). No trial reported data for change in negative symptoms or economic costs.
AUTHORS' CONCLUSIONS
The results of this review show chlorpromazine and piperacetazine may have similar clinical efficacy, but data are based on very small numbers of participants and the evidence is very low quality. We can not make firm conclusions based on such data. Currently, should clinicians and people with schizophrenia need to choose between chlorpromazine and piperacetazine they should be aware there is no good quality evidence to base decisions. More high quality research is needed.
Topics: Adult; Antipsychotic Agents; Chlorpromazine; Female; Humans; Male; Phenothiazines; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 30378678
DOI: 10.1002/14651858.CD011709.pub2 -
The Cochrane Database of Systematic... Apr 2016In the 1940s reserpine, refined from a plant extract that had been used for centuries, began to be used as a treatment for people with mental disorders and was one of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the 1940s reserpine, refined from a plant extract that had been used for centuries, began to be used as a treatment for people with mental disorders and was one of the very first antipsychotic drugs. Its irreversible pharmacological potency and adverse effects meant that it has been withdrawn in the UK and its role has been superceded by 'newer' compounds. The effects of reserpine are of historical interest although there are some reports of it still being used in highly specialist situations in psychiatry. Chlorpromazine is also an old drug but it is still used for treatment of people with schizophrenia.
OBJECTIVES
To investigate the effects of two old medications (reserpine and chlorpromazine) for people with schizophrenia. Reserpine is now rarely used while chlorpromazine remains on the essential list of drugs of the World Health Organization (WHO).
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (24 March 2016).
SELECTION CRITERIA
We included randomised clinical trials focusing on chlorpromazine versus reserpine for schizophrenia that presented useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The review currently includes nine studies with an average 60 participants per study. All of these studies are now over 60 years old, conducted between 1955 and 1962. When chlorpromazine was compared with reserpine for people with schizophrenia, improvement in global state was better at short term for those receiving chlorpromazine (n = 781, 6 RCTs, RR 'not improved' 0.75 95% CI 0.62 to 0.92, low-quality evidence). Short-term improvement in paranoid distortion was measured using the Multidimensional Scale for Rating Psychiatric Patients (MSRPP). Data showed no clear difference between treatment groups (n = 19, 1 RCT, RR 1.33 95% CI 0.62 to 2.89, very low-quality evidence). There was no difference in functioning: occupational adjustment, medium term (n = 40, 1 RCT, RR 0.83 95% CI 0.47 to 1.47, moderate-quality evidence) and general behaviour (n = 98, 1 RCT, RR 0.79 CI 0.41 to 1.53, moderate-quality evidence). Adverse events were poorly reported. For 'toxic reaction' there was, again, no obvious difference between the two compounds (n = 210, 3 RCTs, RR 1.68 95% CI 0.43 to 6.54, moderate-quality evidence), and this also applied to leaving the study early (n = 229, 4 RCTs, RR 1.16 95% CI 0.94 to 1.42, moderate-quality evidence).
AUTHORS' CONCLUSIONS
Judged by standards of today, the evidence is largely of limited quality. However, some of these 1950s studies are remarkable in their foresight and clarity. Reserpine did have some effect on global state - but chlorpromazine did seem to perform better. Important issues regarding adverse effects were not really addressed by these trials. Chlorpromazine remains on the WHO list of essential drugs. Reserpine is now almost obsolete, although, probably as a result of evidence other than that reported in the pioneering trials used in this review.
Topics: Antipsychotic Agents; Chlorpromazine; Humans; Randomized Controlled Trials as Topic; Reserpine; Schizophrenia
PubMed: 27124109
DOI: 10.1002/14651858.CD012122.pub2 -
Journal of Experimental & Clinical... Jan 2020Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical...
BACKGROUND
Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. Tumor recurrence occurs in virtually all cases, therefore, despite any treatment, the median survival is very low (14.6 months), which makes the approach to these patients a challenging clinical issue.
MAIN BODY
The escalating costs and times required for new medications to reach the bedside make repurposing or repositioning of old drugs, when scientific bases allow their use in other pathologies, an appealing strategy. Here, we analyze a number of literature data concerning the antipsychotic chlorpromazine, the founder of the phenothiazines class of drugs, a medication widely used in the clinics for approximately 60 years. The drug exerts its effects on psychiatric patients by interfering with the dopamine receptor D, although more recent pharmacodynamics studies ascribe chlorpromazine a series of biological effects on cancer cells, all converging in hindering also glioblastoma survival capabilities.
SHORT CONCLUSIONS
On these bases, and assisted by the information on the well-established chlorpromazine toxicity and dosage in humans, we designed a Phase II clinical trial involving the combination of chlorpromazine with the standard treatment, temozolomide, in the adjuvant phase of the therapeutic protocol. Patients displaying hypo-methylation of the MGMT gene, and thus intrinsically resistant to temozolomide, will be enrolled. The endpoints of this study are the analysis of toxicity and clinical activity, as evaluated in terms of Progression-Free Survival, of the association of chlorpromazine with the first-line treatment for this very serious form of cancer.
Topics: Brain Neoplasms; Chlorpromazine; Drug Repositioning; Female; Glioblastoma; Humans; Male
PubMed: 32005270
DOI: 10.1186/s13046-020-1534-z -
The Cochrane Database of Systematic... Sep 2014Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic drugs, however,... (Review)
Review
BACKGROUND
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.
OBJECTIVES
To review the effects in clinical response of flupenthixol and low-potency antipsychotics for people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (July 2010).
SELECTION CRITERIA
Randomised controlled trials that compared flupenthixol with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For continuous data, we calculated mean differences (MD) based on a random-effects model.
MAIN RESULTS
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).
AUTHORS' CONCLUSIONS
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.
Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Chlorpromazine; Flupenthixol; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Xerostomia
PubMed: 25177834
DOI: 10.1002/14651858.CD009227.pub2 -
Mediators of Inflammation 2022Cerebral ischemia-reperfusion (I/R) incites neurologic damage through a myriad of complex pathophysiological mechanisms, most notably, inflammation and oxidative stress....
Cerebral ischemia-reperfusion (I/R) incites neurologic damage through a myriad of complex pathophysiological mechanisms, most notably, inflammation and oxidative stress. In I/R injury, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) produces reactive oxygen species (ROS), which promote inflammatory and apoptotic pathways, augmenting ROS production and promoting cell death. Inhibiting ischemia-induced oxidative stress would be beneficial for reducing neuroinflammation and promoting neuronal cell survival. Studies have demonstrated that chlorpromazine and promethazine (C+P) induce neuroprotection. This study investigated how C+P minimizes oxidative stress triggered by ischemic injury. Adult male Sprague-Dawley rats were subject to middle cerebral artery occlusion (MCAO) and subsequent reperfusion. 8 mg/kg of C+P was injected into the rats when reperfusion was initiated. Neurologic damage was evaluated using infarct volumes, neurological deficit scoring, and TUNEL assays. NOX enzymatic activity, ROS production, protein expression of NOX subunits, manganese superoxide dismutase (MnSOD), and phosphorylation of PKC- were assessed. Neural SHSY5Y cells underwent oxygen-glucose deprivation (OGD) and subsequent reoxygenation and C+P treatment. We also evaluated ROS levels and NOX protein subunit expression, MnSOD, and p-PKC-/PKC-. Additionally, we measured PKC- membrane translocation and the level of interaction between NOX subunit (p47) and PKC- via coimmunoprecipitation. As hypothesized, treatment with C+P therapy decreased levels of neurologic damage. ROS production, NOX subunit expression, NOX activity, and p-PKC-/PKC- were all significantly decreased in subjects treated with C+P. C+P decreased membrane translocation of PKC- and lowered the level of interaction between p47 and PKC-. This study suggests that C+P induces neuroprotective effects in ischemic stroke through inhibiting oxidative stress. Our findings also indicate that PKC-, NOX, and MnSOD are vital regulators of oxidative processes, suggesting that C+P may serve as an antioxidant.
Topics: Animals; Brain Injuries; Brain Ischemia; Chlorpromazine; Ischemic Stroke; Male; NADPH Oxidases; Oxidative Stress; Promethazine; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Stroke; Superoxide Dismutase
PubMed: 35873710
DOI: 10.1155/2022/6886752 -
The Cochrane Database of Systematic... Apr 2017The World Health Organization (WHO) Model Lists of Essential Medicines lists chlorpromazine as one of its five medicines used in psychotic disorders. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The World Health Organization (WHO) Model Lists of Essential Medicines lists chlorpromazine as one of its five medicines used in psychotic disorders.
OBJECTIVES
To determine chlorpromazine dose response and dose side-effect relationships for schizophrenia and schizophrenia-like psychoses.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (December 2008; 2 October 2014; 19 December 2016).
SELECTION CRITERIA
All relevant randomised controlled trials (RCTs) comparing low doses of chlorpromazine (≤ 400 mg/day), medium dose (401 mg/day to 800 mg/day) or higher doses (> 800 mg/day) for people with schizophrenia, and which reported clinical outcomes.
DATA COLLECTION AND ANALYSIS
We included studies meeting review criteria and providing useable data. Review authors extracted data independently. For dichotomous data, we calculated fixed-effect risk ratios (RR) and their 95% confidence intervals (CIs). For continuous data, we calculated mean differences (MD) and their 95% CIs based on a fixed-effect model. We assessed risk of bias for included studies and graded trial quality using GRADE (Grading of Recommendations Assessment, Development and Evaluation).
MAIN RESULTS
As a result of searches undertaken in 2014, we found one new study and in 2016 more data for already included studies. Five relevant studies with 1132 participants (585 are relevant to this review) are now included. All are hospital-based trials and, despite over 60 years of chlorpromazine use, have durations of less than six months and all are at least at moderate risk of bias. We found only data on low-dose (≤ 400 mg/day) versus medium-dose chlorpromazine (401 mg/day to 800 mg/day) and low-dose versus high-dose chlorpromazine (> 800 mg/day).When low-dose chlorpromazine (≤ 400 mg/day) was compared to medium-dose chlorpromazine (401 mg/day to 800 mg/day), there was no clear benefit of one dose over the other for both global and mental state outcomes (low-quality and very low-quality evidence). There was also no clear evidence for people in one dosage group being more likely to leave the study early, over the other dosage group (moderate-quality evidence). Similar numbers of participants from each group experienced agitation and restlessness (very low-quality evidence). However, significantly more people in the medium-dose group (401 mg/day to 800 mg/day) experienced extrapyramidal symptoms in the short term (2 RCTS, n = 108, RR 0.47, 95% CI 0.30 to 0.74, moderate-quality evidence). No data for death were available.When low-dose chlorpromazine (≤ 400 mg/day) was compared to high-dose chlorpromazine (> 800 mg/day), data from one study with 416 patients were available. Clear evidence of a benefit of the high dose was found with regards to global state. The low-dose group had significantly fewer people improving (RR 1.13, 95% CI 1.01 to 1.25, moderate-quality evidence). There was also a marked difference between the number of people leaving the study from each group for any reason, with significantly more people leaving from the high-dose group (RR 0.60, 95% CI 0.40 to 0.89, moderate-quality evidence). More people in the low-dose group had to leave the study due to deterioration in behaviour (RR 2.70, 95% CI 1.34 to 5.44, low-quality evidence). There was clear evidence of a greater risk of people experiencing extrapyramidal symptoms in general in the high-dose group (RR 0.43, 95% CI 0.32 to 0.59, moderate-quality evidence). One death was reported in the high-dose group yet no effect was shown between the two dosage groups (RR 0.33, 95% CI 0.01 to 8.14, moderate-quality evidence). No data for mental state were available.
AUTHORS' CONCLUSIONS
The dosage of chlorpromazine has changed drastically over the past 50 years with lower doses now being the preferred of choice. However, this change was gradual and arose not due to trial-based evidence, but due to clinical experience and consensus. Chlorpromazine is one of the most widely used antipsychotic drugs yet appropriate use of lower levels has come about after many years of trial and error with much higher doses. In the absence of high-grade evaluative studies, clinicians have had no alternative but to learn from experience. However, such an approach can lack scientific rigor and does not allow for proper dissemination of information that would assist clinicians find the optimum treatment dosage for their patients. In the future, data for recently released medication should be available from high-quality trials and studies to provide optimum treatment to patients in the shortest amount of time.
Topics: Antipsychotic Agents; Barbiturates; Chloral Hydrate; Chlorpromazine; Drug Administration Schedule; Humans; Hypnotics and Sedatives; Patient Dropouts; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 28407198
DOI: 10.1002/14651858.CD007778.pub2