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Frontiers in Psychiatry 2022Antipsychotics contribute to the development of type 2 diabetes mellitus (T2DM) in individuals with schizophrenia. However, the extent of the relationship between...
BACKGROUND
Antipsychotics contribute to the development of type 2 diabetes mellitus (T2DM) in individuals with schizophrenia. However, the extent of the relationship between antipsychotic use and T2DM varies in different settings, and the magnitude of the drug-specific effects fluctuates widely. This study aimed to explore the association of T2DM with antipsychotic use among enrollees with schizophrenia in China's National Basic Public Health Service Program (NBPHSP) and the drug-specific relationship with T2DM among patients receiving antipsychotic monotherapy.
METHODS
We recruited diabetes-free patients with schizophrenia who were enrolled in the NBPHSP of Hunan Province from October 2009 to December 2018. The participants were classified into the following three groups: regular antipsychotic use, intermittent antipsychotic use, and antipsychotic-free groups. The patients were followed up until they received a T2DM diagnosis or until April 2019. Cox regression models were constructed to calculate the overall and drug-specific hazard ratios (HRs) to determine the antipsychotic-T2DM relationship. Interactive and subgroup analyses were performed to assess the heterogeneity of the effects across subgroups.
RESULTS
A total of 122,064 NBPHSP enrollees with schizophrenia were followed up for 1,507,829 cumulative person-years, and 2,313 (1.89%) patients developed T2DM. Patients who regularly and intermittently used antipsychotics had 117% (HR: 2.17, 95% CI: 1.83-2.57) and 53% (HR: 1.53, 95% CI: 1.23-1.90) higher risks of developing T2DM than antipsychotic-free patients, respectively. Regarding monotherapy, the T2DM risk increased by 66, 80, 62, and 64% after the regular use of clozapine, risperidone, chlorpromazine, and perphenazine, respectively. In addition, the antipsychotic-related risk of T2DM decreased as the patient's baseline body mass index, and baseline fasting plasma glucose level, as well as the dietary proportion of animal products, increased.
CONCLUSION
Antipsychotics, especially clozapine, risperidone, chlorpromazine, and perphenazine, increased the T2DM risk among NBPHSP enrollees with schizophrenia. Mental health officers should accurately identify enrollees at a high risk of T2DM and take appropriate preventive measures to reduce the incidence of T2DM among patients with schizophrenia.
PubMed: 35280179
DOI: 10.3389/fpsyt.2022.754775 -
International Journal of Molecular... May 2020Developing dermatitis therapeutics has been faced with challenges including adverse effects of topical steroid and high cost of new developing drugs. Here, we found the...
Developing dermatitis therapeutics has been faced with challenges including adverse effects of topical steroid and high cost of new developing drugs. Here, we found the expression levels of dopamine receptor D2 is higher in skin biopsies of dermatitis patients and an oxazolone-induced animal model of dermatitis. We used perphenazine, an FDA-approved dopamine receptor antagonist to determine the therapeutic effect. Two different animal models including 12-o-tetradecanoylphorbol-13-acetate (TPA) and oxazolone (OXA)-induced dermatitis were employed. TPA and OXA-mediated ear swelling was attenuated by perphenazine. Moreover, perphenazine inhibited infiltrated mast cells into lesion area. We found levels of serum IgE, histamine and cytokines are decreased in mice cotreated with perphenazine and OXA compared to OXA-treated mice. Overall, this is a first study showing that the FDA-approved, anti-psychotic drug, perphenazine, alleviates animal models of dermatitis.
Topics: Animals; Cytokines; Dermatitis, Allergic Contact; Dopamine Antagonists; Immunoglobulin G; Mast Cells; Mice; Mice, Inbred C57BL; NIH 3T3 Cells; Oxazolone; Perphenazine; Tetradecanoylphorbol Acetate; Th2 Cells
PubMed: 32375285
DOI: 10.3390/ijms21093241 -
Frontiers in Psychiatry 2023Our objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment.
INTRODUCTION
Our objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment.
METHODS
A systematic search was performed in PubMed, Cochrane Central, Embase, Toxline, Ebsco, Virtual Health Library, Web of Science, SpringerLink, and in Database of abstracts of Reviews of Effects of Randomized Clinical Trials to identify eligible studies published from January 1990 to October 2021. The methodological quality of the studies was evaluated using the CONSORT list, and the Cochrane bias tool. Network meta-analysis was performed using the Bayesian random-effects model, with multivariate meta-regression to assess the association of interest.
RESULTS
87 randomized clinical trials were identified that met the inclusion criteria, and 70 articles were included in the network meta-analysis. Regarding the methodological quality of the studies, 47 had a low or moderate bias risk. The most common adverse effects on sleep reported in the studies were insomnia, somnolence, and sedation. The results of the network meta-analysis showed that ziprasidone was associated with an increased risk of insomnia (OR, 1.56; 95% credible interval CrI, 1.18-2.06). Several of the included antipsychotics were associated with a significantly increased risk of somnolence; haloperidol (OR, 1.90; 95% CrI, 1.12-3.22), lurasidone (OR, 2.25; 95% CrI, 1.28-3.97) and ziprasidone (OR, 1.79; 95% CrI, 1.06-3.02) had the narrowest confidence intervals. In addition, perphenazine (OR, 5.33; 95% CrI, 1.92-14.83), haloperidol (OR, 2.61; 95% CrI, 1.14-5.99), and risperidone (OR, 2.41; 95% CrI, 1.21-4.80) were associated with an increased risk of sedation compared with placebo, and other antipsychotics did not differ. According to the SUCRAs for insomnia, chlorpromazine was ranked as the lowest risk of insomnia (57%), followed by clozapine (20%), while flupentixol (26 %) and perospirone (22.5%) were associated with a lower risk of somnolence. On the other hand, amisulpride (89.9%) was the safest option to reduce the risk of sedation.
DISCUSSION
Insomnia, sedation, and somnolence were the most frequent adverse effects on sleep among the different antipsychotics administered. The evidence shows that chlorpromazine, clozapine, flupentixol, perospirone, and amisulpride had favorable safety profiles. In contrast, ziprasidone, perphenazine, haloperidol, and risperidone were the least safe for sleep.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017078052, identifier: PROSPERO 2017 CRD42017078052.
PubMed: 37441144
DOI: 10.3389/fpsyt.2023.1189768 -
Current Neuropharmacology 2023Since the early clinical efficacy of antipsychotics has not yet been well perceived, this study sought to decide whether the efficacy of antipsychotics at week 2 can... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
Since the early clinical efficacy of antipsychotics has not yet been well perceived, this study sought to decide whether the efficacy of antipsychotics at week 2 can predict subsequent responses at week 6 and identify how such predictive capacities vary among different antipsychotics and psychotic symptoms.
METHODS
A total of 3010 patients with schizophrenia enrolled in a randomized controlled trial (RCT) and received a 6-week treatment with one antipsychotic drug randomly chosen from five atypical antipsychotics (risperidone 2-6 mg/d, olanzapine 5-20 mg/d, quetiapine 400-750 mg/d, aripiprazole 10-30 mg/d, and ziprasidone 80-160 mg/d) and two typical antipsychotics (perphenazine 20-60 mg/d and haloperidol 6-20 mg/d). Early efficacy was defined as the reduction rate using the Positive and Negative Syndrome Scale (PANSS) total score at week 2. With cut-offs at 50% reduction, logistic regression, receiver operating characteristic (ROC) and random forests were adopted.
RESULTS
The reduction rate of PANSS total score and improvement of psychotic symptoms at week 2 enabled subsequent responses to 7 antipsychotics to be predicted, in which improvements in delusions, lack of judgment and insight, unusual thought content, and suspiciousness/ persecution were endowed with the greatest weight.
CONCLUSION
It is robust enough to clinically predict treatment responses to antipsychotics at week 6 using the reduction rate of PANSS total score and symptom relief at week 2. Psychiatric clinicians had better determine whether to switch the treatment plan by the first 2 weeks.
Topics: Humans; Antipsychotic Agents; Benzodiazepines; Schizophrenia; Aripiprazole; Olanzapine; Risperidone; Quetiapine Fumarate; Haloperidol; Treatment Outcome
PubMed: 36411567
DOI: 10.2174/1570159X21666221118164612 -
Psychological Medicine Mar 2021Individuals diagnosed with psychiatric disorders who are prescribed antipsychotics have lower rates of violence and crime but the differential effects of specific...
BACKGROUND
Individuals diagnosed with psychiatric disorders who are prescribed antipsychotics have lower rates of violence and crime but the differential effects of specific antipsychotics are not known. We investigated associations between 10 specific antipsychotic medications and subsequent risks for a range of criminal outcomes.
METHODS
We identified 74 925 individuals who were ever prescribed antipsychotics between 2006 and 2013 using nationwide Swedish registries. We tested for five specific first-generation antipsychotics (levomepromazine, perphenazine, haloperidol, flupentixol, and zuclopenthixol) and five second-generation antipsychotics (clozapine, olanzapine, quetiapine, risperidone, and aripiprazole). The outcomes included violent, drug-related, and any criminal arrests and convictions. We conducted within-individual analyses using fixed-effects Poisson regression models that compared rates of outcomes between periods when each individual was either on or off medication to account for time-stable unmeasured confounders. All models were adjusted for age and concurrent mood stabilizer medications.
RESULTS
The relative risks of all crime outcomes were substantially reduced [range of adjusted rate ratios (aRRs): 0.50-0.67] during periods when the patients were prescribed antipsychotics v. periods when they were not. We found that clozapine (aRRs: 0.28-0.44), olanzapine (aRRs: 0.46-0.72), and risperidone (aRRs: 0.53-0.64) were associated with lower arrest and conviction risks than other antipsychotics, including quetiapine (aRRs: 0.68-0.84) and haloperidol (aRRs: 0.67-0.77). Long-acting injectables as a combined medication class were associated with lower risks of the outcomes but only risperidone was associated with lower risks of all six outcomes (aRRs: 0.33-0.69).
CONCLUSIONS
There is heterogeneity in the associations between specific antipsychotics and subsequent arrests and convictions for any drug-related and violent crimes.
PubMed: 33691828
DOI: 10.1017/S0033291721000556 -
British Journal of Anaesthesia Jul 1999The past decade has witnessed the introduction of several significant innovations to combat POV, particularly the introduction of serotonin antagonists and the use of... (Review)
Review
The past decade has witnessed the introduction of several significant innovations to combat POV, particularly the introduction of serotonin antagonists and the use of combinations of drugs for analgesia and control of POV. Based on current knowledge, the anaesthetic plan for a patient with a previous history of severe PONV and undergoing a procedure known to be associated with a high incidence of this problem should include premedication with a benzodiazepine and/or clonidine and the preferential use of regional anaesthetic techniques. If general anaesthesia is essential, anaesthetists should consider the use of propofol for both induction and maintenance of anaesthesia, together with avoidance of nitrous oxide, opioids and neuromuscular antagonists. Pain control is extremely important, and a peripheral regional block should be used if possible. A combination of prophylactic antiemetics such as dexamethasone, a 5-HT3 antagonist and an antiemetic of a different class (e.g. perphenazine or dimenhydrinate) should be administered. Non-pharmacological measures such as acupressure and suggestion should also be considered, together with nursing measures to avoid sudden movement from one position to another during the postoperative period. A quiet environment, adequate i.v. fluids and not forcing the patient to drink before discharge all contribute to decreased emesis. It is possible that the advent of a new class of antiemetic agents, the NKI antagonists, may have major effects on the incidence of this complication. Drugs in this group differ from other currently available drugs in having the ability to effectively block the emetic response to many stimuli in experimental animals. Postoperative vomiting remains a significant problem, resulting in patient suffering and prolonged recovery from anaesthesia. Our aim should be to eliminate this complication in all children who require surgery. It should not be considered merely as the 'big, little problem'.
Topics: Antiemetics; Child; Humans; Postoperative Nausea and Vomiting; Research Design; Risk Factors
PubMed: 10616338
DOI: 10.1093/bja/83.1.104 -
The International Journal of... Nov 2013The N-methyl-D-aspartate receptor (NMDAR) antagonists, phencyclidine (PCP), dizocilpine (MK-801), or ketamine, given subchronically (sc) to rodents and primates, produce... (Review)
Review
The N-methyl-D-aspartate receptor (NMDAR) antagonists, phencyclidine (PCP), dizocilpine (MK-801), or ketamine, given subchronically (sc) to rodents and primates, produce prolonged deficits in cognitive function, including novel object recognition (NOR), an analog of human declarative memory, one of the cognitive domains impaired in schizophrenia. Atypical antipsychotic drugs (AAPDs) have been reported to improve declarative memory in some patients with schizophrenia, as well as to ameliorate and prevent the NOR deficit in rodents following scNMDAR antagonist treatment. While the efficacy of AAPDs to improve cognitive impairment in schizophrenia (CIS) is limited, at best, and controversial, single doses of all currently available AAPDs so far tested transiently restore NOR in rodents following scNMDAR antagonist treatment. Typical antipsychotic drugs (APDs), e.g. haloperidol and perphenazine, are ineffective in this rodent model, and may be less effective as treatments of some domains of CIS. Serotonergic mechanisms, including, but not limited to serotonin (5-HT)2A and 5-HT7 antagonism, 5-HT(1A), and GABA(A) agonism, contribute to the efficacy of the AAPDs in the scNMDAR antagonist rodent models, which are relevant to the loss of GABA interneuron/hyperglutamate hypothesis of the etiology of CIS. The ability of sub-effective doses of the atypical APDs to ameliorate NOR in the scNMDAR-treated rodents can be restored by the addition of a sub-effective dose of the 5-HT(1A) partial agonist, tandospirone, or the 5-HT7 antagonist, SB269970. The mGluR2/3 agonist, LY379268, which itself is unable to restore NOR in the scNMDAR-treated rodents, can also restore NOR when given with lurasidone, an AAPD. Enhancing cortical and hippocampal dopamine and acetylcholine efflux, or both, may contribute to the restoration of NOR by the atypical APDs. Importantly, co-administration of lurasidone, tandospirone, or SB269970, with PCP, to rodents, at doses 5-10 fold greater than those acutely effective to restore NOR following scNMDAR treatment, prevents the effect of scPCP to produce an enduring deficit in NOR. This difference in dosage may be relevant to utilizing AAPDs to prevent the onset of CIS in individuals at high risk for developing schizophrenia. The scNMDAR paradigm may be useful for identifying possible means to treat and prevent CIS.
Topics: Animals; Antipsychotic Agents; Behavior, Animal; Brain; Cognition; Cognition Disorders; Disease Models, Animal; Excitatory Amino Acid Antagonists; Humans; Receptors, N-Methyl-D-Aspartate; Receptors, Serotonin; Recognition, Psychology; Schizophrenia; Schizophrenic Psychology; Serotonin; Translational Research, Biomedical
PubMed: 24099265
DOI: 10.1017/S1461145713000928 -
Psychiatry Investigation Dec 2012I report here an elderly woman receiving perphenazine together with terbinafine. After 1 week of terbinafine treatment she experienced extrapyramidal symptoms and, in...
I report here an elderly woman receiving perphenazine together with terbinafine. After 1 week of terbinafine treatment she experienced extrapyramidal symptoms and, in particular, akathisia. Her symptoms did not disappear for 6 weeks, and so at 2 weeks prior to this most recent admission she had stopped taking terbinafine. However, these symptoms persisted for 3 weeks after discontinuing terbinafine. It is well known that terbinafine inhibits CYP2D6 and that perphenazine is metabolized mainly by CYP2D6. Thus, when terbinafine and perphenazine are coadministrated, the subsequent increase in the concentration of perphenazine may induce extrapyramidal symptoms. Thus, terbinafine therapy may be associated with the induction and persistence of extrapyramidal symptoms, including akathisia. This case report emphasizes the importance of monitoring drug-drug interactions in patients undergoing terbinafine and perphenazine therapy.
PubMed: 23251210
DOI: 10.4306/pi.2012.9.4.422 -
BioMed Research International 2021Perphenazine (PPZ), as a typical antipsychotic medical substance, has the same effectiveness compared to atypical antipsychotic medications for the treatment of...
OBJECTIVE
Perphenazine (PPZ), as a typical antipsychotic medical substance, has the same effectiveness compared to atypical antipsychotic medications for the treatment of schizophrenia. Despite the lipophilic essence, PPZ encounters limited bioavailability caused by the first-pass metabolism following oral administration. In the present study, PPZ-containing solid lipid nanoparticles (PPZ-SLNs) were prepared and optimized based on different factors, including lipid and surfactant amount, to develop appropriate and safe novel oral dosage forms of PPZ.
METHODS
The solvent emulsification-evaporation method was utilized to form SLNs by using soybean lecithin, glycerol monostearate (GMS), and Tween 80. Statistical optimization was done by the Box-Behnken design method to achieve formulation with optimized particle size, entrapment efficiency, and zeta potential. Also, transmission electron microscopy, release behavior, differential scanning calorimetry (DSC), and powder X-ray diffractometry (P-XRD) studies and cytotoxicity studies were assessed.
RESULTS
Optimization exhibited the significant effect of various excipients on SLN characteristics. Our finding indicated that the mean particle size, zeta potential, and entrapment efficiency of optimized PPZ-SLN were, respectively, 104 ± 3.92 nm, -28 ± 2.28 mV, and 83% ± 1.29. Drug release of PPZ-SLN was observed to be greater than 90% for 48 h that emphasized a sustained-release pattern. The DSC and P-XRD studies revealed the amorphous state of PPZ-SLN. FTIR spectra showed no incompatibility between the drug and the lipid. Performing cytotoxicity studies indicated no significant cytotoxicity on HT-29 cell culture.
CONCLUSION
Our study suggests that PPZ-SLNs can make a promising vehicle for a suitable therapy of schizophrenia for the oral drug delivery system.
Topics: Calorimetry, Differential Scanning; Cell Death; Cell Survival; Drug Liberation; HT29 Cells; Humans; Lipids; Models, Biological; Nanoparticles; Particle Size; Perphenazine; Reproducibility of Results; Spectroscopy, Fourier Transform Infrared; Static Electricity; Statistics as Topic; X-Ray Diffraction
PubMed: 33997026
DOI: 10.1155/2021/6619195 -
Proceedings of the Royal Society of... Mar 1973
Review
Topics: Amitriptyline; Anthracenes; Antidepressive Agents; Anxiety; Diazepam; Dibenzazepines; Humans; Lactates; Limbic System; Monoamine Oxidase Inhibitors; Perphenazine; Psychosurgery
PubMed: 4572667
DOI: No ID Found