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The Primary Care Companion For CNS... Apr 2023
Topics: Humans; Olanzapine; Schizophrenia; Antipsychotic Agents; Psychotic Disorders; Weight Loss; Benzodiazepines
PubMed: 37027805
DOI: 10.4088/PCC.21cr03113 -
International Journal of Molecular... May 2023As a partial histamine H1 receptor agonist and H3 antagonist, betahistine has been reported to partially prevent olanzapine-induced dyslipidemia and obesity through a...
As a partial histamine H1 receptor agonist and H3 antagonist, betahistine has been reported to partially prevent olanzapine-induced dyslipidemia and obesity through a combination therapy, although the underlying epigenetic mechanisms are still not known. Recent studies have revealed that histone regulation of key genes for lipogenesis and adipogenesis in the liver is one of the crucial mechanisms for olanzapine-induced metabolic disorders. This study investigated the role of epigenetic histone regulation in betahistine co-treatment preventing dyslipidemia and fatty liver caused by chronic olanzapine treatment in a rat model. In addition to abnormal lipid metabolism, the upregulation of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), as well as the downregulation of carnitine palmitoyltransferase 1A (CPT1A) in the liver induced by olanzapine, were significantly attenuated by betahistine co-treatment. In addition, betahistine co-treatment significantly enhanced the global expression of H3K4me and the enrichment of H3K4me binding on the promoter of gene as revealed by ChIP-qPCR, but inhibited the expression of one of its site-specific demethylases, lysine (K)-specific demethylase 1A (KDM1A). Betahistine co-treatment also significantly enhanced the global expression of H3K9me and the enrichment of H3K9me binding on the promoter of the gene, but inhibited the expression of two of its site-specific demethylases, lysine demethylase 4B (KDM4B) and PHD finger protein 2 (PHF2). These results suggest that betahistine attenuates abnormal adipogenesis and lipogenesis triggered by olanzapine through modulating hepatic histone methylation, and thus inhibiting the PPARγ pathway-mediated lipid storage, while at the same time promoting CP1A-mediated fatty acid oxidation.
Topics: Rats; Animals; Olanzapine; Betahistine; PPAR gamma; Histones; Methylation; Carnitine O-Palmitoyltransferase; Lysine; Benzodiazepines; Dyslipidemias; Epigenesis, Genetic
PubMed: 37298094
DOI: 10.3390/ijms24119143 -
The Cochrane Database of Systematic... Dec 2015This is an updated version of the original Cochrane review published in Issue 4, 2008.People suffering from epilepsy have an increased risk of experiencing psychotic... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 4, 2008.People suffering from epilepsy have an increased risk of experiencing psychotic symptoms. The psychotic syndromes associated with epilepsy have generally been classified as ictal, postictal, and interictal psychosis. Anticonvulsant drugs have been reported to precipitate psychosis. Moreover, all antipsychotic drugs have the propensity to cause paroxysmal electroencephalogram abnormalities and induce seizures.
OBJECTIVES
To evaluate the benefits of interventions used to treat clinically significant psychotic symptoms occurring in people with epilepsy with regard to global improvement, changes in mental state, hospitalization, behavior, quality of life, effect on the frequency of seizures, and interaction with antiepileptic drugs.
SEARCH METHODS
We searched the Cochrane Epilepsy Group's Specialized Register (23 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies Online (CRSO), 23 March 2015), MEDLINE (Ovid, 1946 to 23 March 2015), PsycINFO (1887 to 23 March 2015), CINAHL (1937 to 23 March 2015), and BIOSIS Previews (1969 to 23 March 2015).Two review authors (SF and AS) independently inspected the citations identified from the search. We identified potentially relevant abstracts and assessed full papers for inclusion and methodological quality.
SELECTION CRITERIA
All randomized controlled trials comparing drugs, behavior therapy, cognitive behavior therapy, or other non-pharmacological interventions used to relieve psychotic symptoms in people with epilepsy.
DATA COLLECTION AND ANALYSIS
We planned to extract and analyze the data from all relevant studies using standardized methods. As only one study met the inclusion criteria, we attempted no meta-analysis.
MAIN RESULTS
After independently assessing the abstracts and titles of 618 articles, we selected five relevant abstracts. Ultimately we found only one study meeting the inclusion criteria, which was available only as an abstract. This study compared the use of olanzapine (10 mg/day) with haloperidol (12 mg/day) in 16 people suffering from schizophrenia-like psychosis of epilepsy. Thirteen participants completed the study. Significant improvement was associated with use of olanzapine. We did not identify any study on psychosocial interventions in people suffering from epilepsy and psychosis.
AUTHORS' CONCLUSIONS
We found only one randomized controlled trial, which lacked the power to test the efficacy of antipsychotics in those suffering from psychosis concomitant with epilepsy.Limited evidence from this small randomized controlled trial suggests an improvement in psychotic symptoms, but not other outcome measures, with the use of an antipsychotic. The effects on seizure control are not well studied. Further trials are required to inform practice.
Topics: Antipsychotic Agents; Benzodiazepines; Epilepsy; Humans; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 26690687
DOI: 10.1002/14651858.CD006118.pub3 -
General Hospital Psychiatry 2023Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of... (Randomized Controlled Trial)
Randomized Controlled Trial
Does drug use affect the efficacy of amisulpride, aripiprazole and olanzapine in patients with schizophrenia spectrum disorders? Results from a pragmatic, randomised study.
OBJECTIVES
Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of antipsychotic medication. This secondary explorative study compared the effectiveness of three antipsychotics in patients with SSD, with and without drug use.
METHODS
The BeSt InTro multi-centre, head to head, rater-blinded randomised study compared amisulpride, aripiprazole and olanzapine over a 1-year follow-up period. All patients (n = 144) were aged ≥18 years and met the ICD-10 criteria for SSD (F20-29). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The primary outcome was reduction of a PANSS positive subscale score.
RESULTS
At baseline, 38% of all patients reported drug use in the last 6 months before inclusion, with cannabis as the main drug (85%), followed by amphetamine-type stimulants (45%), sedatives (26%), hallucinogens (19%), cocaine (13%), opiates (4%), GHB (4%), solvents (4%), analgesics (4%) and anabolic steroids (2%). The predominant pattern was the use of several drugs. There were no significant overall differences in the PANSS positive subscale score reduction for the three studied antipsychotics among patients either with or without drug use. In the drug use group, older patients treated with amisulpride showed a greater PANSS positive subscale score reduction during the treatment period compared to younger patients.
CONCLUSION
The current study showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use.
Topics: Humans; Adolescent; Adult; Olanzapine; Aripiprazole; Antipsychotic Agents; Schizophrenia; Amisulpride; Clozapine; Risperidone; Benzodiazepines; Piperazines; Thiazoles; Treatment Outcome
PubMed: 37269769
DOI: 10.1016/j.genhosppsych.2023.05.003 -
Cancer Treatment Reviews Apr 2023Several regimens have been introduced in clinical practice in the last twenty years to treat chemotherapy-induced nausea and vomiting (CINV). However, direct comparative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several regimens have been introduced in clinical practice in the last twenty years to treat chemotherapy-induced nausea and vomiting (CINV). However, direct comparative data remain insufficient, as many new regimes lack head-to-head comparisons. In this study, through an indirect comparison, we overcome this limit by providing the most up-to-date estimate of the efficacy and safety of all combinations used for HEC-induced nausea and vomiting.
PATIENTS AND METHODS
We retrieved randomized controlled trials (RCTs) published in Pubmed, Embase, and Cochrane Library until June, 30th 2022. We included phase II-III RCTs, including adults with any cancer receiving HEC, and compared different antiemetic regimes to prevent CINV. The primary outcome was the overall complete response (defined as the absence of vomiting and of the use of rescue drugs from 0 to 120 hrs since chemotherapy); secondary outcomes were acute (absence of vomiting and use of rescue medicine 0-24 hrs after chemotherapy) and delayed (24-120 hrs) response and adverse events.
RESULTS
A total of 53 RCTs enrolling 22 228 patients were included. We classified the different antiemetic regimes into 21 different groups. Overall, 3- or 4-drug regimens containing a combination of dexamethasone, 5HT3 antagonists, mirtazapine or olanzapine with or without NK antagonists, yielded the highest probability to be the most effective regimen in terms of complete response. Regimens containing a combination of dexamethasone and 5-HT3 antagonist have the lowest probability of being the most effective regimen in terms of complete, acute, and delayed response.
CONCLUSION
In our network meta-analysis, 4-drug regimens with olanzapine displayed the highest probability of efficacy in terms of complete response. A 3-drug regimen with olanzapine represents a valid option in a limited resource context.
Topics: Adult; Humans; Antiemetics; Antineoplastic Agents; Dexamethasone; Nausea; Network Meta-Analysis; Olanzapine; Vomiting
PubMed: 36774658
DOI: 10.1016/j.ctrv.2023.102512 -
Scientific Reports Oct 2023Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using...
Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The present work focused on the impact of CYP1A2 and CYP2D6 genetic polymorphisms as well as of CYP1A2 metabolizing capacity influenced by non-genetic factors (sex, age, smoking) on olanzapine blood concentration in patients with psychiatric disorders (N = 139). CYP2D6 genotype-based phenotype appeared to have negligible contribution to olanzapine metabolism, whereas a dominant role of CYP1A2 in olanzapine exposure was confirmed. However, CYP1A2 expression rather than CYP1A2 genetic variability was demonstrated to be associated with olanzapine concentration in patients. Significant contribution of - 163C > A (rs762551), the most common SNP (single nucleotide polymorphism) in CYP1A2 gene, to enhanced inducibility was confirmed by an increase in CYP1A2 mRNA expression in smokers carrying - 163A, and smoking was found to have appreciable impact on olanzapine concentration normalized by the dose/bodyweight. Furthermore, patients' olanzapine exposure was in strong association with CYP1A2 expression; therefore, assaying CYP1A2 mRNA level in leukocytes can be an appropriate tool for the estimation of patients' olanzapine metabolizing capacity and may be relevant in optimizing olanzapine dosage.
Topics: Humans; Olanzapine; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2D6; Antipsychotic Agents; Genotype; RNA, Messenger
PubMed: 37898643
DOI: 10.1038/s41598-023-45752-6 -
JAMA Network Open May 2023It is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
It is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of randomized clinical trials using olanzapine may provide insight into the effectiveness of olanzapine for chemotherapy-induced nausea and vomiting (CINV), including cisplatin.
OBJECTIVE
To examine the add-on effect of olanzapine according to risk factors for CINV.
DESIGN, SETTING, AND PARTICIPANTS
This preplanned secondary analysis evaluated results of the J-FORCE trial, a large double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Japan from February 9, 2017, to July 18, 2018. Participants were enrolled from 26 participating hospitals across Japan and included patients aged 20 to 75 years who had a malignant tumor and were cisplatin-naive. The efficacy analysis population of the J-FORCE trial was analyzed according to allocation adjustment factors (sex [male or female], age [≥55 years or <55 years], and cisplatin dose [≥70 mg/m2 or <70 mg/m2]) and patient-related risk factors (history of motion sickness, drinking habit [defined as alcoholic drinks consumption in excess of occasional drinking], and history of morning sickness during pregnancy). Statistical analysis was performed from February 18 to April 18, 2020.
INTERVENTIONS
Patients were randomized 1:1 to receive 5 mg of olanzapine or placebo combined with standard triplet antiemetic therapy.
MAIN OUTCOMES AND MEASURES
The primary end point was complete response (CR, defined as no vomiting and no use of rescue medication) in the delayed phase (24-120 hours after cisplatin-based chemotherapy administration). Secondary end points were CR, complete control, and total control in the acute, delayed, and overall phases for 6 CINV risk factors as well as time to treatment failure. The CR point estimates and 95% CIs of the differences between groups were calculated, and a Mantel-Haenszel test was performed.
RESULTS
Of the 705 patients (mean [SD] age, 63.0 [9.2] years; 471 males [66.8%]) included in the efficacy analysis population; 581 patients (82.4%) were 55 years or older, and 526 (74.6%) were treated with a cisplatin dose of 70 mg/m2 or more. Risk difference (RD) for a CR in the delayed phase was significantly greater in the olanzapine group than the placebo group in males (RD, 12.6% [95% CI, 5.0%-20.1%]; P = .001); in females (RD, 14.5% [95% CI, 2.2%-26.3%]; P = .02); in those 55 years or older (RD, 11.1% [95% CI, 3.9%-18.2%]; P = .003) or younger than 55 years (RD, 23.6% [95% CI, 7.3%-38.3%]; P = .005); for a cisplatin dose of 70 mg/m2 or more (RD, 13.5% [95% CI, 5.9%-21.0%]; P < .001); for those without a history of motion sickness (RD, 13.9% [95% CI, 6.9%-20.6%]; P < .001); for those with a drinking habit (RD, 14.9% [95% CI, 6.1%-23.4%]; P = .001) or without a drinking habit (RD, 12.0% [95% CI, 2.5%-21.3%]; P = .01); and for those with a history of morning sickness during pregnancy (RD, 27.2% [9.7%-42.6%]; P = .002). In other subgroups, a delayed CR was higher in the olanzapine group than the placebo group, although not significantly higher.
CONCLUSIONS AND RELEVANCE
Results of this study suggest a benefit of using 5 mg of olanzapine plus triplet antiemetic therapy to counter CINV regardless of the presence or absence of risk factors.
TRIAL REGISTRATION
University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000024676.
Topics: Humans; Male; Female; Pregnancy; Middle Aged; Antiemetics; Olanzapine; Cisplatin; Vomiting; Nausea; Motion Sickness; Morning Sickness
PubMed: 37129897
DOI: 10.1001/jamanetworkopen.2023.10894 -
The American Journal of Case Reports Nov 2021BACKGROUND Drug-induced acute angle closure glaucoma is an uncommon ocular emergency that may follow the administration of certain topical and systemic medications....
BACKGROUND Drug-induced acute angle closure glaucoma is an uncommon ocular emergency that may follow the administration of certain topical and systemic medications. Acute angle closure can be triggered by various classes of drugs, including adrenergic agonists, anticholinergics, and serotonergic medications. Here, we report a rare case of drug-induced acute angle closure glaucoma secondary to olanzapine. CASE REPORT A 59-year-old male patient of Arabian Peninsula descent, known to have schizophrenia, presented to our Emergency Department with a 3-day history of right ocular pain and decrease in vision. He was started recently on olanzapine 5 mg once daily by his psychiatrist 1 week prior to the onset of his symptoms. The diagnosis of drug-induced pupillary block was made based on clinical and radiological findings. The patient was started on topical and systemic IOP-lowering agents. A therapeutic Nd: YAG laser peripheral iridotomy for the right eye was performed. On follow-up, his symptoms alleviated and clinical examination showed significant improvement. CONCLUSIONS The reported case highlights the importance of systemic medical history in secondary acute angle closure glaucoma. Physicians from other specialties should be aware of drugs triggering pupillary block and therefore be able to educate patients about symptoms of acute angle closure glaucoma.
Topics: Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Iris; Laser Therapy; Male; Middle Aged; Olanzapine
PubMed: 34803156
DOI: 10.12659/AJCR.934432 -
Journal of Clinical Pharmacology Nov 2021A combination of olanzapine and samidorphan was recently approved by the US Food and Drug Administration for the treatment of patients with schizophrenia or bipolar I...
A combination of olanzapine and samidorphan was recently approved by the US Food and Drug Administration for the treatment of patients with schizophrenia or bipolar I disorder. Population pharmacokinetic models for olanzapine and samidorphan were developed using data from 11 clinical studies in healthy subjects or patients with schizophrenia. A 2-compartment disposition model with first-order absorption and elimination and a lag time for absorption adequately described concentration-time profiles of both olanzapine and samidorphan. Age, sex, race, smoking status, and body weight were identified as covariates that impacted the pharmacokinetics of olanzapine. A moderate effect of body weight on samidorphan pharmacokinetics was identified by the model but was not considered clinically meaningful. The effects of food, hepatic or renal impairment, and coadministration with rifampin on the pharmacokinetics of olanzapine and samidorphan, as estimated by the population pharmacokinetic analysis, were consistent with findings from dedicated clinical studies designed to evaluate these specific covariates of interest. Food intake did not have a clinically relevant effect on the pharmacokinetics of olanzapine or samidorphan. Consistent with the known metabolic pathways for olanzapine (primarily via uridine 5'-diphospho-glucuronosyltransferase-mediated direct glucuronidation and cytochrome P450 [CYP]-mediated oxidation) and for samidorphan (predominantly mediated by CYP3A4), coadministration of olanzapine and samidorphan with rifampin, a strong inducer of CYP3A4 and an inducer of uridine 5'-diphospho-glucuronosyltransferase enzymes, significantly decreased the systemic exposure of both olanzapine and samidorphan. Severe renal impairment or moderate hepatic impairment resulted in a modest increase in olanzapine and samidorphan exposure.
Topics: Adolescent; Adult; Age Factors; Aged; Antipsychotic Agents; Body Weight; Cigarette Smoking; Cytochrome P-450 CYP3A; Drug Combinations; Female; Food-Drug Interactions; Humans; Liver Failure; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Olanzapine; Racial Groups; Renal Insufficiency; Rifampin; Schizophrenia; Sex Factors; Young Adult
PubMed: 34018607
DOI: 10.1002/jcph.1911 -
Journal of Applied Physiology... Feb 2021Olanzapine (OLZ) is used in the treatment of schizophrenia and a growing number of "off-label" conditions. Although effective in reducing psychoses, OLZ causes rapid...
Olanzapine (OLZ) is used in the treatment of schizophrenia and a growing number of "off-label" conditions. Although effective in reducing psychoses, OLZ causes rapid impairments in glucose and lipid homeostasis. The purpose of this study was to investigate if voluntary physical activity via wheel running (VWR) would protect against the acute metabolic side effects of OLZ. Male C57BL/6J mice remained sedentary or were provided with running wheels overnight, before treatment with OLZ either at the beginning of the light cycle, or 7 or 24 h following the cessation of VWR. Prior VWR protected against OLZ-induced hyperglycemia immediately and 7 h following a bout of overnight wheel running. Protection against, hyperglycemia immediately following VWR was associated with increased insulin tolerance and an attenuated OLZ-induced increase in the serum glucagon:insulin ratio. The protective effect of VWR against OLZ-induced increases in hyperglycemia and glucagon:insulin ratio was maintained in high-fat fed, and AMPK β1-deficient mice, models which display a potentiated OLZ-induced increase in blood glucose. Repeated OLZ treatment did not impair VWR performance and protection against the acute effects of OLZ on blood glucose was present after 1 wk of daily OLZ treatment in mice given access to running wheels. In contrast to the effects on glucose metabolism, VWR, for the most part, did not impact OLZ-induced perturbations in lipolysis, liver triglyceride accumulation, or whole body substrate oxidation. Collectively, our findings demonstrate the efficacy of voluntary physical activity as an approach to protect against OLZ-induced impairments in glucose metabolism. The antipsychotic medication olanzapine causes rapid and large increases in blood glucose. We demonstrate that a prior bout of voluntary overnight wheel running can protect against this harmful side effect and is likely mediated by reductions in olanzapine-induced increases in the circulating glucagon to insulin ratio. This study highlights the powerful effects of voluntary activity in conditions of treatment with antipsychotic medications.
Topics: Animals; Blood Glucose; Hyperglycemia; Male; Mice; Mice, Inbred C57BL; Motor Activity; Olanzapine
PubMed: 33382959
DOI: 10.1152/japplphysiol.00876.2020