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Journal of Pharmaceutical and... Oct 2020Hair analysis is a useful tool for establishing long-term drug intake. Segmental analysis, in particular, where the hair is cut into defined segments, can potentially...
Hair analysis is a useful tool for establishing long-term drug intake. Segmental analysis, in particular, where the hair is cut into defined segments, can potentially provide a calendar of patients' drug intake as drugs are incorporated into the growing hair through the bloodstream with an average growth rate of 1 cm per month. Forensic investigations of hair require knowledge of typical concentrations of common pharmaceuticals in hair, which are rarely reported. The aim of this study was to provide values for olanzapine and N-desmethyl-olanzapine concentrations in postmortem hair from chronic olanzapine consumers to contribute to the establishment of a reference interval for this drug. We analyzed postmortem head hair samples from 37 suspected mentally ill patients, who were part of the SURVIVE population, a Danish national autopsy-based study. Each sample was cut into 1 cm segments, and up to six segments, corresponding to up to six months of hair growth prior to death, were analyzed depending on the hair length. The hair extracts were analyzed by liquid chromatography tandem mass spectrometry. Olanzapine and N-desmethyl-olanzapine were added to a published and validated method. The 37 patients were 12 females and 25 males aged 25-81 years. Their hair colors varied from blond to black, with the majority brown, thus no trend could be discerned from the hair colors. Drugs other than olanzapine were found in all cases except one, and illicit drugs were found in the hair samples of 38 % of the cases. We report olanzapine concentrations ranging from 0.005-20.9 ng/mg (median 0.128 ng/mg) and N-desmethyl-olanzapine concentrations from 0.027 to 0.187 ng/mg (median 0.068 ng/mg) for all 141 analyzed segments. Metabolite-to-drug ratios ranged from 0.010 to 3.31 (median 0.590). Dose calculations based on prescription pick-up demonstrated no correlation with the concentrations in hair, but olanzapine concentrations in the proximal hair segment correlated significantly with olanzapine concentrations in postmortem blood. Olanzapine concentrations decreased considerably from the proximal to distal segments, emphasizing the importance of reporting the length of the measured hair when reporting drug concentrations in hair. This study can contribute to the establishment of a reference interval for olanzapine and N-desmethyl-olanzapine concentrations in hair by reporting concentrations in hair from chronic consumers.
Topics: Adult; Aged; Aged, 80 and over; Autopsy; Chromatography, High Pressure Liquid; Chromatography, Liquid; Female; Forensic Toxicology; Hair Analysis; Humans; Male; Mentally Ill Persons; Middle Aged; Olanzapine; Pirenzepine; Tandem Mass Spectrometry
PubMed: 32814260
DOI: 10.1016/j.jpba.2020.113510 -
Annals of Palliative Medicine Mar 2021Olanzapine has been found to have antiemetic properties due to its ability to inhibit multiple serotonergic, dopaminergic, alpha-1 adrenergic and histamine receptors. In... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Olanzapine has been found to have antiemetic properties due to its ability to inhibit multiple serotonergic, dopaminergic, alpha-1 adrenergic and histamine receptors. In 2016, a meta-analysis of 10 randomized controlled trials (RCTs) on olanzapine in the prophylactic setting found olanzapine to be more efficacious than other standard antiemetics in the prophylactic setting. However, since the review, many clinical trials using olanzapine for chemotherapy-induced nausea and vomiting (CINV) have been published-in many cases, contending that further trials would further help elucidate the efficacy of olanzapine for CINV given the continued paucity of literature. The primary aim of this study is to conduct a secondary, cumulative meta-analysis to assess the impact of the most recent trials on the published effect estimate of olanzapine and ultimately determine whether trials published since 2016 have significantly changed the summary estimate.
METHODS
As reported previously, a literature search was conducted up until 2015, of Ovid Medline, Embase and the Cochrane Central Register of Controlled Trials; 10 RCTs with a total of over 1,000 patients were included, that compared olanzapine to other antiemetics in the prophylactic setting, which reported on at least one of two endpoints-no emesis and no nausea. The Mantel-Haenszel, random-effects analysis model was used to compute cumulative risk ratios (RR) and their accompanying 95% confidence intervals (CIs).
RESULTS
For the endpoint of emetic control, the cumulative meta-analysis shows that the summary effect did not change noticeably with the inclusion of the most recent trials. In the acute phase, the RR shifted from 1.07 before 2011 to 1.10 after 2015, even after the inclusion of 7 trials. Similar small changes were noted in the delayed and overall phases. For the endpoint of nausea control, the cumulative meta-analysis does show a significant visual change in summary effect, except for nausea control in the acute phase. In the delayed phase, the RR shifts from 1.58 before 2011 to 1.50 after 2015. In the overall phase, the RR shifts from 1.642 before 2011 to 1.53 after 2015.
CONCLUSIONS
Olanzapine's efficacy for the prophylaxis of CINV has been sufficiently documented, with respect to emetic control. There is, however, more limited data supporting its efficacy with respect to nausea control.
Topics: Antiemetics; Antineoplastic Agents; Humans; Nausea; Olanzapine; Vomiting
PubMed: 33440973
DOI: 10.21037/apm-20-1462 -
Molecular Psychiatry Jun 2021Schizophrenia is a chronic and severe mental disorder that affects over 20 million people worldwide. Common symptoms include distortions in thinking, perception,... (Review)
Review
Schizophrenia is a chronic and severe mental disorder that affects over 20 million people worldwide. Common symptoms include distortions in thinking, perception, emotions, language, and self awareness. Different hypotheses have been proposed to explain the development of schizophrenia, however, there are no unifying features between the proposed hypotheses. Schizophrenic patients have perturbed levels of glucose in their cerebrospinal fluid, indicating a disturbance in glucose metabolism. We have explored the possibility that disturbances in glucose metabolism can be a general mechanism for predisposition and manifestation of the disease. We discuss glucose metabolism as a network of signaling pathways. Glucose and glucose metabolites can have diverse actions as signaling molecules, such as regulation of transcription factors, hormone and cytokine secretion and activation of neuronal cells, such as microglia. The presented model challenges well-established concepts in enzyme kinetics and glucose metabolism. We have developed a 'two-cell' model of glucose metabolism, which can explain the effects of electroconvulsive therapy and the beneficial and side effects of olanzapine treatment. Arrangement of glycolytic enzymes into metabolic signaling complexes within the 'two hit' hypothesis, allows schizophrenia to be formulated in two steps. The 'first hit' is the dysregulation of the glucose signaling pathway. This dysregulation of glucose metabolism primes the central nervous system for a pathological response to a 'second hit' via the astrocytic glycogenolysis signaling pathway.
Topics: Antipsychotic Agents; Cytokines; Glucose; Humans; Microglia; Olanzapine; Schizophrenia
PubMed: 33402704
DOI: 10.1038/s41380-020-00980-4 -
Behavioural Pharmacology Apr 20232,5-dimethoxy-4-methylamphetamine (DOM) is a kind of hallucinogen of phenylalkylamine. Psychedelic effects mainly include audiovisual synesthesia, complex imagery,...
2,5-dimethoxy-4-methylamphetamine (DOM) is a kind of hallucinogen of phenylalkylamine. Psychedelic effects mainly include audiovisual synesthesia, complex imagery, disembodiment etc. that can impair control and cognition leading to adverse consequences such as suicide. By now, there are no specific drugs regarding the management of classic hallucinogen use clinically. We evaluated the effects of three 5-HT 2A receptor antagonists ketanseirn, M100907 and olanzapine on hallucination-like behavior in therapeutic and preventive administration with male C57BL/6J mice. Two models were used to evaluate the therapeutic potential of antagonists, one is head-twitch response (HTR) and the other is locomotion. Effects of ketanserin, M100907 and olanzapine on DOM-induced HTR were studied in preventive and therapeutic administration, respectively. In the preventive administration, the ID 50 values of ketanseirn, M100907 and olanzapine were 0.4 mg/kg, 0.005 mg/kg and 0.25 mg/kg. In the therapeutic administration, the ID 50 values of ketanseirn, M100907 and olanzapine were 0.04 mg/kg, 0.005 mg/kg and 0.03 mg/kg. Secondly, locomotor activity induced by DOM was performed to further evaluate the efficacy of three compounds. In locomotion, M100907(0.005 mg/kg) whenever in preventive or therapeutic administration, reduced the increase of movement distance induced by DOM. Although ketanserin (0.4 mg/kg) in the preventive administration also decreased the movement distance induced by DOM, it was alone administrated to influence the locomotor activity. Through HTR and locomotion, we compared the efficacy and latent side effects of ketanserin, M100907 and olanzapine against hallucinogenic like action induced by DOM. Our study provided additional experimental evidence on specific therapeutic drugs against hallucinogenic behavior induce by representative hallucinogen DOM.
Topics: Mice; Animals; Male; Ketanserin; DOM 2,5-Dimethoxy-4-Methylamphetamine; Hallucinogens; Olanzapine; Methamphetamine; Mice, Inbred C57BL; Receptor, Serotonin, 5-HT2A
PubMed: 36752335
DOI: 10.1097/FBP.0000000000000693 -
Psychiatry Research Apr 2023Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no...
Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.
Topics: Humans; Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Chronic Disease; Hyperprolactinemia; Olanzapine; Piperazines; Quinolones; Recurrence; Schizophrenia
PubMed: 36871411
DOI: 10.1016/j.psychres.2023.115138 -
Medicine Dec 2022Chemotherapy-induced nausea and vomiting (CINV) is a serious side effect of chemotherapy that negatively impacts the quality of life of oncological patients and is... (Review)
Review
Chemotherapy-induced nausea and vomiting (CINV) is a serious side effect of chemotherapy that negatively impacts the quality of life of oncological patients and is associated with the emetogenic risk specific to administered chemotherapy. Current practice guidelines on the use of antiemetics in CINV include the option of adding olanzapine to antiemetic regimens in the management of adult CINV. The use of olanzapine in pediatric CINV has been restricted to children with poor CINV control. Research on the use of olanzapine in pediatric CINV has been limited. The aim of this review was to evaluate current evidence on the effective and safe antiemetic use of olanzapine in pediatric CINV of any type following chemotherapy of any emetogenicity. Ovid MEDLINE, Embase, CENTRAL databases were searched for any literature on the use of olanzapine in pediatric CINV published from 2015 to 2022. Studies that reported on the olanzapine-containing antiemetic regimen in peadiatric CINV control specifically were included. Search restrictions were placed on research published in English. The search generated 43 records that were assessed for eligibility. Out of 10 identified eligible studies a third were RCT. Findings of this review suggest that adding olanzapine to antiemetic regimen in pediatric CINV control is a worthwhile consideration. Further research is needed to establish the efficacy and safety of antiemetic olanzapine use in pediatric CINV.
Topics: Adult; Humans; Child; Antiemetics; Olanzapine; Quality of Life; Antineoplastic Agents; Nausea; Vomiting
PubMed: 36550859
DOI: 10.1097/MD.0000000000032116 -
The Lancet. Psychiatry Apr 2022Combining antipsychotics is common in schizophrenia treatment, despite evidence-based guidelines generally not recommending such practice. Otherwise, evidence remains... (Randomized Controlled Trial)
Randomized Controlled Trial
Amisulpride and olanzapine combination treatment versus each monotherapy in acutely ill patients with schizophrenia in Germany (COMBINE): a double-blind randomised controlled trial.
BACKGROUND
Combining antipsychotics is common in schizophrenia treatment, despite evidence-based guidelines generally not recommending such practice. Otherwise, evidence remains inconclusive, especially regarding specific combinations. The trial aimed to test whether a combination of amisulpride plus olanzapine is more effective than either intervention as a monotherapy.
METHODS
A multicentre, 16-week, randomised, double-blind, controlled trial was done at 16 psychiatric in-patient centres throughout Germany. Inclusion criteria were adults aged 18-65 years with non-first episode schizophrenia or schizoaffective disorder and with a Positive and Negative Syndrome Scale (PANSS) total score of at least 70 and at least two items of the positive symptoms subscale rated at least 4. Patients were randomly assigned to receive 16 weeks of treatment with either amisulpride plus olanzapine, amisulpride plus placebo, or olanzapine plus placebo (1:1:1), and block randomisation was stratified by study site. To keep patients and investigators masked throughout the duration of the trial, amisulpride, olanzapine, and placebo were administered as identical capsules. Flexibly dosed monotherapy of oral amisulpride (amisulpride plus placebo, 200-800 mg per day) or olanzapine (olanzapine plus placebo, 5-20 mg per day) was compared with a combination of amisulpride plus olanzapine. The primary outcome was symptom reduction measured by the PANSS total score after 8 weeks, in the modified intention-to-treat population (all patients randomly assigned to an intervention and receiving at least one study drug dose). As determined a priori, group differences were examined by t tests (Bonferroni-Holm-adjustment) followed by pre-planned Bayesian analyses as well as imputation methods based on mixed models to account for missing values and post-hoc ANCOVA adjusting for PANSS baseline scores. The study was registered on ClinicalTrials.gov, NCT01609153; the German Clinical Trials Register, DRKS00003603; and the European Union Drug Regulating Authorities Clinical Trials Database, EudraCT-No. 2011-002463-20.
FINDINGS
Between June 15, 2012, and Dec 15, 2018, 13 692 patients were assessed for eligibility. 13 364 patients were excluded (including for not meeting inclusion criteria, declining to participate, or inappropriate reasons for changing pharmacological treatment), and 328 were then randomly assigned to an intervention group. 112 patients were randomly assigned to receive amisulpride plus olanzapine, 109 were randomly assigned to receive amisulpride plus placebo, and 107 were randomly assigned to receive olanzapine plus placebo. 321 patients were analysed for the primary outcome in the modified intention-to-treat population after exclusion of screening failures and patients who did not receive the intervention (110 for amisulpride plus olanzapine, 109 for amisulpride plus placebo, and 102 for olanzapine plus placebo). Among the 321 patients who were randomly assigned to intervention groups and analysed for the primary outcome, 229 (71%) were male, 92 (29%) were female; the mean age was 40·2 years (SD 11·7); and 296 (92%) were White and 25 (8%) were classified as other ethnicity. PANSS total score improved significantly more at 8 weeks in the amisulpride plus olanzapine group (-29·6 [SD 14·5]) than in the olanzapine plus placebo group (-24·1 [13·4], p=0·049, Cohen's d=0·396). A significant difference was not observed in reduction of PANSS total score between the amisulpride and olanzapine group compared with the amisulpride and placebo group (-25·2 [SD 15·9], p=0·095, Cohen's d=0·29). After 8 weeks and 16 weeks, sexual dysfunction, weight, and waist circumference increase were significantly higher for patients receiving amisulpride plus olanzapine than for those receiving amisulpride plus placebo, with no differences in serious adverse events. Two patients died during study participation; one randomly assigned to the amisulpride plus olanzapine group, and one assigned to the olanzapine plus placebo group (both assessed with no relation to treatment).
INTERPRETATION
The advantages of amisulpride plus olanzapine have to be weighed against a higher propensity for side-effects. The use of this specific combination therapy could be an alternative to monotherapy in certain clinical situations, but side-effects should be considered.
FUNDING
German Federal Ministry of Education and Research.
Topics: Adolescent; Adult; Aged; Amisulpride; Bayes Theorem; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Schizophrenia; Treatment Outcome; Young Adult
PubMed: 35276079
DOI: 10.1016/S2215-0366(22)00032-3 -
European Neuropsychopharmacology : the... Jun 2023The atypical antipsychotic drug olanzapine is prescribed despite clinical studies on olanzapine treatment showing mixed results on treatment efficacy in anorexia...
The atypical antipsychotic drug olanzapine is prescribed despite clinical studies on olanzapine treatment showing mixed results on treatment efficacy in anorexia nervosa. We investigated the effect of systemic and intranasal administration of olanzapine in the activity-based anorexia (ABA) model. Rats were habituated to a running wheel and exposed to the ABA model while treated with olanzapine. During ABA rats had 1.5 h of daily access to food and ad libitum access to a running wheel for seven consecutive days. Olanzapine was administered via an osmotic minipump (1, 2.75, and 7.5 mg/kg) or intranasally 2 h before dark onset (1 and 2.75 mg/kg). We monitored body weight, food intake, wheel revolutions, body temperature, and adipose tissue. We found 2.75 and 7.5 mg/kg systemic olanzapine decreased wheel revolutions during ABA. Relative adipose tissue mass was increased in the 7.5 mg/kg olanzapine-treated group while body weight, food intake, and body temperature were unaltered by the systemic olanzapine. 1 and 2.75 mg/kg intranasal olanzapine diminished wheel revolutions and body temperature during the first 2 h after administration. The intranasal olanzapine-treated rats had a higher body weight at the end of ABA. We find that olanzapine has beneficial outcomes in the ABA via two administration routes by acting mainly on running wheel activity. Intranasal olanzapine showed a rapid effect in the first hours after administration in reducing locomotor activity. We recommend further exploring intranasal administration of olanzapine in anorectic patients to assist them in coping with restlessness.
Topics: Rats; Animals; Olanzapine; Anorexia; Administration, Intranasal; Body Weight; Anorexia Nervosa; Eating; Disease Models, Animal
PubMed: 37031523
DOI: 10.1016/j.euroneuro.2023.03.008 -
Journal of Pain and Symptom Management Oct 2023Current palliative care guidelines lack a specific treatment algorithm for nausea and emesis. Olanzapine is an atypical antipsychotic with antiemetic activity that's...
CONTEXT
Current palliative care guidelines lack a specific treatment algorithm for nausea and emesis. Olanzapine is an atypical antipsychotic with antiemetic activity that's recommended in the guidelines for the treatment of chemotherapy induced nausea and vomiting, but outside of oncologic indications there is a lack of research.
OBJECTIVES
To describe the safety and efficacy of olanzapine for nausea and emesis in the palliative care domain, excluding patients actively undergoing chemotherapy or radiation.
METHODS
This retrospective chart review encompassed hospitalized adult patients from six hospitals across a large health system admitted from August 2020 through August 2021, with a palliative care consult, and being treated with olanzapine for nausea or emesis. Data was collected on antiemetic therapy affordability, the ability for patients to tolerate medications by mouth, and safety outcomes such as QTc prolongation and increased liver function tests.
RESULTS
A total of 78 patients were included in the study. Olanzapine decreased the number of doses required of antiemetic medications, the median doses of antiemetic medications pre-olanzapine was 1.6 (IQR 0.8-2.8) and post-olanzapine was 0.6 (IQR 0-2.4) (P = 0.0006). After olanzapine was initiated, appetite was improved (P < 0.001), cost of antiemetic therapy was reduced by 65 cents per day (P = 0.059) and olanzapine was prescribed at discharge in 69% of patients. QTc prolongation was observed in 19% of patients, and increased ALT and AST were observed in 4.3% and 0%, respectively.
CONCLUSION
This retrospective review demonstrated benefit to utilizing olanzapine for nausea and emesis in palliative care patients and should be considered to aid in symptom management.
Topics: Adult; Humans; Antiemetics; Olanzapine; Vomiting; Palliative Care; Retrospective Studies; Nausea; Gastrointestinal Agents; Long QT Syndrome; Antineoplastic Agents
PubMed: 37348739
DOI: 10.1016/j.jpainsymman.2023.06.019 -
BMC Psychiatry Jun 2023Antipsychotic treatment may improve clinical insight. However, previous studies have reported inconclusive findings on whether antipsychotics improve insight over and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Antipsychotic treatment may improve clinical insight. However, previous studies have reported inconclusive findings on whether antipsychotics improve insight over and above the reduction in symptoms of psychosis. These studies assessed homogeneous samples in terms of stage of illness. Randomised studies investigating a mixed population of first- and multiepisode schizophrenia spectrum disorders might clarify this disagreement.
METHODS
Our data were derived from a pragmatic, rater-blinded, semi-randomised trial that compared the effectiveness of amisulpride, aripiprazole and olanzapine. A sample of 144 patients with first- or multiepisode schizophrenia spectrum disorders underwent eight assessments during a 1-year follow-up. Clinical insight was assessed by item General 12 from the Positive and Negative Syndrome Scale (PANSS). We analysed latent growth curve models to test if the medications had a direct effect on insight that was over and above the reduction in total psychosis symptoms. Furthermore, we investigated whether there were differences between the study drugs in terms of insight.
RESULTS
Based on allocation analysis, all three drugs were associated with a reduction in total psychosis symptoms in the initial phase (weeks 0-6). Amisulpride and olanzapine were associated with improved insight over and above what was related to the reduction in total psychosis symptoms in the long-term phase (weeks 6-52). However, these differential effects were lost when only including the participants that chose the first drug in the randomisation sequence. We found no differential effect on insight among those who were antipsychotic-naïve and those who were previously medicated with antipsychotics.
CONCLUSIONS
Our results suggest that antipsychotic treatment improves insight, but whether the effect on insight surpasses the effect of reduced total psychosis symptoms is more uncertain.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01446328, 05.10.2011.
Topics: Humans; Schizophrenia; Olanzapine; Aripiprazole; Antipsychotic Agents; Amisulpride
PubMed: 37386462
DOI: 10.1186/s12888-023-04981-9