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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 -
Translational Psychiatry Feb 2022QTc interval prolongation is one of the most common antipsychotic-induced side effects which could lead to ventricular tachycardia or Torsade de Pointes, even cardiac... (Randomized Controlled Trial)
Randomized Controlled Trial
QTc interval prolongation is one of the most common antipsychotic-induced side effects which could lead to ventricular tachycardia or Torsade de Pointes, even cardiac arrest. There is very limited understanding on the genetic factors that associated with antipsychotic-induced QTc interval change. We conducted a genome-wide association study (GWAS) of antipsychotic-induced QTc interval change among patients with schizophrenia. A total of 2040 patients with schizophrenia were randomly assigned to six groups (olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, and first-generation antipsychotics; first-generation antipsychotics including haloperidol or perphenazine were also assigned randomly) and received 6-week antipsychotic treatment. We identified two novel loci (rs200050752 in ATAD3B and rs186507741 in SKIL) that were associated with antipsychotic-induced QTc interval change at a genome-wide significance level. The combination of polygenic risk score (PRS), based the GWAS of myocardial infarction from BioBank Japan project, and clinical data (sex, heart rate and QTc interval at baseline) could be applied to predict whether patients with schizophrenia have QTc interval prolongation (10 ms was applied as threshold, P < 0.001, area under the curve [AUC] was 0.797), especially for the first episode patients (P < 0.001, AUC was 0.872). We identified two loci located within genes related to mitochondrial function and cell growth and differentiation, which were both associated with schizophrenia and heart function. The combination of PRS and clinical data could predict whether patients with schizophrenia have the side effect of QTc interval prolongation, which could fundamentally guide the choice of antipsychotic in patients with schizophrenia, especially for the first-episode patients.
Topics: ATPases Associated with Diverse Cellular Activities; Antipsychotic Agents; Electrocardiography; Genome-Wide Association Study; Humans; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Mitochondrial Proteins; Proto-Oncogene Proteins; Risperidone; Schizophrenia
PubMed: 35136033
DOI: 10.1038/s41398-022-01825-0 -
Psychiatrische Praxis Jul 2022A 57-year-old female patient with unclear somnolence was admitted to an Intermediate Care Unit (IMC) by an emergency physician. Several psychotropic drugs were on the...
A 57-year-old female patient with unclear somnolence was admitted to an Intermediate Care Unit (IMC) by an emergency physician. Several psychotropic drugs were on the medication list (quetiapine 450 mg/d, paroxetine 40 mg/d and perphenazine 12 mg/d), due to depression with psychotic features. As the patient's state deteriorated on day 3, she was intubated and transferred to Intensive Care Unit (ICU), where a malignant hyperthermia (MH) was assumed. The ICU's call to the MH hotline did not give a hint to consider a neuroleptic malignant syndrome (NMS) neither to consider electroconvulsive therapy (ECT). It was not until day 9 that a psychiatric consultation was undertaken, under the suspected diagnosis of NMS. On the same day ECT was performed, followed by a rapid remission of all clinical features and laboratory findings. Early consideration and application of ECT treatment for NMS on an ICU is life-saving.
Topics: Antipsychotic Agents; Electroconvulsive Therapy; Female; Germany; Humans; Intensive Care Units; Middle Aged; Neuroleptic Malignant Syndrome
PubMed: 35081629
DOI: 10.1055/a-1702-2345 -
Journal of AOAC International Apr 2022Anesthetics and sedatives are frequently used to prevent abrasions caused by stress and to facilitate fish management. However, drug residues may persist and cause...
BACKGROUND
Anesthetics and sedatives are frequently used to prevent abrasions caused by stress and to facilitate fish management. However, drug residues may persist and cause changes in fish conditions and induce side effects. In addition, drugs that are not permitted for use in edible fish are sometimes potentially used in fish. The drugs can also be found in wastewater and are likely to be detected in fish.
OBJECTIVE
The purpose of this study was to establish a quantitative analytical method for 10 anesthetic and sedative (azaperone, chlorpromazine, diazepam, estazolam, haloperidol, nitrazepam, nordiazepam, oxazepam, perphenazine, and temazepam) residues in fish sold in Korean markets.
METHOD
Shrimp, flounder, and eel samples were selected as matrices. Acetonitrile (ACN) containing 0.1% formic acid was selected as an extraction solvent for shrimp and 100% ACN for flounder and eel. The QuEChERS method with C18 and primary secondary amine (PSA) was used as the extraction procedure, and the analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
RESULTS
Limit of quantitation, recovery, accuracy, and precision were validated, and satisfactory results were obtained for the drugs. All results applied to the real samples were negative.
CONCLUSIONS
An optimal validation method was studied. Since the results for all samples were negative, it is considered that additional studies are needed by increasing the number of drugs.
HIGHLIGHTS
The most effective QuEChERS pretreatment method and conditions of LC-MS/MS for the analysis of anesthetics and sedatives in fish were established.
Topics: Anesthetics; Animals; Chromatography, Liquid; Drug Residues; Fishes; Hypnotics and Sedatives; Limit of Detection; Tandem Mass Spectrometry
PubMed: 34894253
DOI: 10.1093/jaoacint/qsab155 -
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 -
Biological & Pharmaceutical Bulletin 2021The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease,...
The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clinically available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clinically significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders.
Topics: Acetylcholine; Aging; Animals; Antipsychotic Agents; Chlorpromazine; Cholinergic Antagonists; Clozapine; Dibenzothiepins; Male; Mental Disorders; Methotrimeprazine; Muscle Contraction; Muscle, Smooth; Olanzapine; Quetiapine Fumarate; Rats, Wistar; Urinary Bladder; Urologic Diseases; Rats
PubMed: 34334499
DOI: 10.1248/bpb.b21-00363 -
Schizophrenia Bulletin Jan 2022People with schizophrenia/schizoaffective disorder (schizophrenia) die early, largely due to cardiovascular-related mortality. Antipsychotics are associated with lower...
Antipsychotics Use Is Associated With Greater Adherence to Cardiometabolic Medications in Patients With Schizophrenia: Results From a Nationwide, Within-subject Design Study.
BACKGROUND
People with schizophrenia/schizoaffective disorder (schizophrenia) die early, largely due to cardiovascular-related mortality. Antipsychotics are associated with lower mortality. We aimed to explore whether antipsychotic use can reduce discontinuation of medications for cardiovascular risk factors and diseases ("cardiometacolic drugs"), using a within-study design controlling for subject-related factors.
METHODS
Persons diagnosed with schizophrenia between 1972 and 2014, aged <65 years at cohort entry were identified in Finnish national databases. Four subcohorts were formed based on cardiometabolic drug use during the follow-up period, 1996-2017, namely statin (n = 14,047), antidiabetic (n = 13,070), antihypertensive (n = 17,227), and beta-blocker (n = 21,464) users. To control for subject-related factors, including likelihood of adherence as a trait characteristic, we conducted a within-subject study comparing the risk of discontinuation of each cardiometabolic drug during periods on vs off antipsychotics within each subject. We also accounted for number of psychiatric and nonpsychiatric visits in sensitivity analyses.
RESULTS
In 52,607 subjects with schizophrenia, any antipsychotic use vs nonuse was associated with decreased discontinuation risk of antidiabetics (adjusted hazard ratio [aHR] = 0.56, 95% confidence interval [CI] = 0.47-0.66), statins (aHR = 0.61, 95%CI = 0.53-0.70), antihypertensives (aHR = 0.63, 95%CI = 0.56-0.71), and beta-blockers (aHR = 0.79, 95%CI = 0.73-0.87). Antipsychotics ranking best for discontinuation of all cardiometabolic drug categories were clozapine (aHR range = 0.34-0.55), followed by olanzapine (aHR = 0.43-0.71). For statins, aHRs ranged from aHR = 0.30 (95%CI = 0.09-0.98) (flupentixol-long-acting injectable (LAI) to aHR = 0.71 (95%CI = 0.52-0.97) (risperidone-LAI), for anti-diabetic medications from aHR = 0.37 (95%CI = 0.28-0.50) (clozapine) to aHR = 0.70 (95%CI = 0.53-0.92) (quetiapine), for antihypertensives from aHR = 0.14 (95%CI = 0.04-0.46) (paliperidone-LAI) to aHR = 0.69 (95%CI = 0.54-0.88) (perphenazine), for beta-blockers from aHR = 0.55 (95%CI = 0.48-0.63) (clozapine) to aHR = 0.76 (95%CI = 0.59-0.99) (perphenazine-LAI). The decreased risk of discontinuation associated with antipsychotic use somewhat varied between age strata. Sensitivity analyses confirmed main findings.
DISCUSSION
In this national database within-subject design study, current antipsychotic use was associated with substantially decreased risk of discontinuation of statins, anti-diabetics, antihypertensives, and beta-blockers, which might explain reduced cardiovascular mortality observed with antipsychotics in people with schizophrenia.
Topics: Adrenergic beta-Antagonists; Adult; Antihypertensive Agents; Antipsychotic Agents; Cardiovascular Diseases; Comorbidity; Female; Finland; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Male; Medication Adherence; Metabolic Diseases; Middle Aged; Schizophrenia
PubMed: 34286338
DOI: 10.1093/schbul/sbab087 -
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 -
Biomedical Chromatography : BMC Sep 2021A UPLC-MS/MS method was developed to determine the levels of five traditional antipsychotics (APs) (chlorprothixene, perphenazine, fluphenazine, thioridazine, and...
A UPLC-MS/MS method was developed to determine the levels of five traditional antipsychotics (APs) (chlorprothixene, perphenazine, fluphenazine, thioridazine, and promethazine) in human plasma with carbamazepine as the internal standard. Samples were extracted using simple liquid-liquid extraction (ethyl acetate/methyl tert-butyl ether, 2:3 v/v); then the analytes were subjected to gradient elution chromatography with a mobile phase composed of 0.1% formic acid in water and acetonitrile. The analytes were separated using a Waters XBridge BEH C column (100 × 2.1 mm, 2.5 μm). The linear ranges of chlorprothixene, perphenazine, fluphenazine, thioridazine, and promethazine are 2-250 ng/mL, r > 0.995. The limit of quantitation is 2 ng/mL, and the limit of detection is in the range of 0.1-0.5 ng/mL. The inter-day and intra-day relative standard deviations are less than 10%, and the relative errors are in the range of -5.70 to 7.20%. The recoveries of the five drugs are in the range of 70-109%. The results of methodology verification indicate that this method is simple, economical, sensitive, and suitable for the simultaneous quantification of five traditional APs in human plasma.
Topics: Adult; Aged; Antipsychotic Agents; Chromatography, High Pressure Liquid; Female; Humans; Limit of Detection; Linear Models; Liquid-Liquid Extraction; Male; Middle Aged; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 33856061
DOI: 10.1002/bmc.5143 -
Neuroscience and Biobehavioral Reviews Jul 2021Cognitive deficits are a core aspect of psychotic disorders; however, it is not clear to which extent different pharmacological treatments could distinctly impact these... (Review)
Review
Cognitive deficits are a core aspect of psychotic disorders; however, it is not clear to which extent different pharmacological treatments could distinctly impact these outcomes. Hence, we conducted a systematic review and ten network meta-analyses of randomized controlled trials to compare the effect of antipsychotics on cognitive performance of individuals with psychotic disorders. Fifty-four trials were included in the analyses, enrolling 5866 patients. Compared to other antipsychotics, amisulpride performed better on verbal learning; quetiapine on composite score, attention and verbal learning; lurasidone on composite score; olanzapine on composite score and most cognitive domains; perphenazine on composite score, executive function, working memory, and verbal learning; risperidone on executive function and verbal learning; sertindole on processing speed; and ziprasidone on composite score, working memory, and verbal learning. Oppositely, haloperidol performed poorer on all cognitive domains, occupying the last positions in all rankings; and clozapine performed poorer on composite score, executive function, verbal learning, and visuoconstruction. We hope that these results should be taken into account when assessing and treating individuals with psychosis.
Topics: Antipsychotic Agents; Benzodiazepines; Cognition; Humans; Network Meta-Analysis; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 33812977
DOI: 10.1016/j.neubiorev.2021.03.028