olanzapine and Neoplasms

Chemotherapy-induced nausea and vomiting (CINV) remain the most distressing event in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This meta-analysis was conducted to evaluate the efficacy and safety of olanzapine containing regimen in preventing CINV in children on HEC and MEC. We searched PubMed, Embase, and Cochrane central register of controlled trials electronic databases to identify randomized clinical trials that compared 2 groups who either got olanzapine (olanzapine group) or placebo/no olanzapine (control group) for the prevention of CINV in children. The primary outcome was to determine the efficacy of olanzapine (complete response). The secondary outcomes were nausea control, the need for rescue medications, and adverse events of olanzapine. Three randomized clinical trials (n=394 patients) were included in this meta-analysis (olanzapine group, n=194, and placebo/control group, n=200). The pooled analysis of this meta-analysis found that olanzapine had a higher complete response in all phases of emesis in the HEC group and only in the acute phase in HEC/MEC groups compared with the control group. Olanzapine had higher nausea control in all phases of HEC but no nausea control in HEC/MEC. Olanzapine also reduced the need for rescue medications. A significant number of patients in the olanzapine group experienced somnolence (grades 1 and 2), but none of the participants discontinued the study due to side effects. In conclusion, this meta-analysis showed that olanzapine significantly prevented CINV in HEC. There was also a lesser need for rescue medications in the olanzapine group. Somnolence was higher in the olanzapine group, but it was clinically insignificant.

Topics: Antiemetics; Antineoplastic Agents; Child; Humans; Nausea; Neoplasms; Olanzapine; Randomized Controlled Trials as Topic; Sleepiness; Vomiting

Olanzapine is an effective antipsychotic drug used in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders. It belongs to the 2nd generation antipsychotics, its mechanism of action ranks among multireceptor antagonists (MARTA); it affects the dopamine, serotonin, adrenaline, histamine, and muscarinic systems. The broad pharmacodynamic profile of olanzapine provides for a broad indication spectrum with a better adverse effect profile compared to conventional antipsychotics. It can be used in a number of situations to benefit cancer patients in palliative care as well as in the terminal stages of the disease.. The review article presents possible indications for olanzapine in oncological palliative care. Apart from dealing with delirium and anxiety, indications for the use of antipsychotics in palliative medicine include the management of nausea, vomiting and loss of appetite. Olanzapine is an effective antiemetic in cancer patients with tumor-induced nausea and in antiemetic regimens for chemotherapy-induced nausea and vomiting. Olanzapine is an effective treatment for delirium, as effective as haloperidol, but with a lower toxicity profile. It increases appetite and can be used with advantage in patients with anorexia and weight loss. It is possible to use its anxiolytic and mood-stabilizing effects; in many situations, it can serve well as a co-analgesic, especially in the so-called total pain. It is proven to increase the quality of life of patients with advanced cancer.. Due to its effect, simple dosage and a good safety profile, olanzapine is a useful drug for the routine clinical practice of an oncologist - a non-psychiatrist.

Topics: Antiemetics; Antipsychotic Agents; Delirium; Humans; Nausea; Neoplasms; Olanzapine; Palliative Care; Quality of Life; Vomiting

Olanzapine has become a major drug in the management of chemotherapy-induced nausea and vomiting as a prophylactic agent. In addition, a recent randomized trial has demonstrated its benefits in treating nausea and vomiting associated with advanced cancer. The added benefit to olanzapine is that it also stimulates appetite. As a result, since it treats multiple symptoms associated with advanced cancer, it is likely to become the antiemetic of choice in palliative care at least in the USA. The added benefit of treating insomnia and the avoidance of benzodiazepines should place olanzapine in at the top of the list of drugs to use for patients who do complain of insomnia. There is no good evidence that it potentiates the respiratory depression of opioids unlike benzodiazepines. The evidence is weak that olanzapine in as an adjuvant analgesic. Hopefully, future trials will explore this in greater depth. The benefits of adding olanzapine to potent opioids are that it may reduce craving, drug cues, and opioid misuse. Other symptoms like anxiety and depression may be addressed by the addition of olanzapine to standard antidepressants.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Antipsychotic Agents; Drug Monitoring; Humans; Nausea; Neoplasms; Olanzapine; Palliative Care; Postoperative Complications; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Vomiting

Cancer patients always experience an ongoing deterioration in health-related quality of life (HRQoL). There is a strengthening awareness of health care professionals of taking HRQoL, which is a patient-reported outcome measures (PROMs), into consideration when they make an adequate selection in clinical practice. Olanzapine, an antipsychotic agent, has been demonstrated to be a safe and effective agent in improving cancer-related symptoms.. To review the efficacy and safety of olanzapine in improving HRQoL among adults with malignant tumor.. Eligible studies were retrieved from an electronic database search of the Cochrane, Medline, CINAHL plus, Pubmed, Embase, PsycINFO, Web of Science, and Scopus. The methodological quality of selected studies was evaluated, and the relevant data were extracted and synthesized.. While studies differed in target population, olanzapine-based treatment regimen, and HRQoL measurement tools, results have shown that olanzapine has a positive impact on cancer patients' general HRQoL status, functional outcomes, and/or symptoms improvement. Besides, no serious toxicities attributable to olanzapine were observed in all studies included.. While further studies are needed especially which adopted the HRQoL as primary outcome through comprehensive measures, olanzapine could still be recommended in the palliative care.

Topics: Antineoplastic Combined Chemotherapy Protocols; Antipsychotic Agents; Cancer Survivors; Humans; Neoplasms; Olanzapine; Patient Reported Outcome Measures; Quality of Life; Treatment Outcome

It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis.. Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided.. We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56-1.97, and OR, 2.25; 95% CrI, 1.66-3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR.. Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients.. Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Drug Costs; Humans; Nausea; Neoplasms; Network Meta-Analysis; Olanzapine; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Vomiting

Regulators of G protein signaling (RGS) are a family of proteins classically known to accelerate the intrinsic GTPase activity of G proteins, which results in accelerated inactivation of heterotrimeric G proteins and inhibition of G protein coupled receptor signaling. RGS proteins play major roles in essential cellular processes, and dysregulation of RGS protein expression is implicated in multiple diseases, including cancer, cardiovascular and neurodegenerative diseases. The expression of RGS proteins is highly dynamic and is regulated by epigenetic, transcriptional and post-translational mechanisms. This review summarizes studies that report dysregulation of RGS protein expression in disease states, and presents examples of drugs that regulate RGS protein expression. Additionally, this review discusses, in detail, the transcriptional and post-transcriptional mechanisms regulating RGS protein expression, and further assesses the therapeutic potential of targeting these mechanisms. Understanding the molecular mechanisms controlling the expression of RGS proteins is essential for the development of therapeutics that indirectly modulate G protein signaling by regulating expression of RGS proteins.

Topics: Animals; Azacitidine; Benzodiazepines; Cardiovascular Diseases; Drugs, Investigational; Epigenesis, Genetic; GTP-Binding Proteins; Humans; Hydroxamic Acids; Neoplasms; Neurodegenerative Diseases; Olanzapine; Protein Processing, Post-Translational; RGS Proteins; Signal Transduction; Vorinostat

Olanzapine as an antiemetic represents a new use of an antipsychotic drug. People with cancer may experience nausea and vomiting whilst receiving chemotherapy or radiotherapy, or whilst in the palliative phase of illness.. To assess the efficacy and safety of olanzapine when used as an antiemetic in the prevention and treatment of nausea and vomiting related to cancer in adults.. We searched CENTRAL, MEDLINE and Embase for published data on 20th September 2017, as well as ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform for unpublished trials. We checked reference lists, and contacted experts in the field and study authors.. We included randomised controlled trials (RCTs) of olanzapine versus any comparator with or without adjunct therapies for the prevention or treatment, or both, of nausea or vomiting in people with cancer aged 18 years or older, in any setting, of any duration, with at least 10 participants per treatment arm.. We used standard Cochrane methodology. We used GRADE to assess quality of evidence for each main outcome. We extracted data for absence of nausea or vomiting and frequency of serious adverse events as primary outcomes. We extracted data for patient perception of treatment, other adverse events, somnolence and fatigue, attrition, nausea or vomiting severity, breakthrough nausea and vomiting, rescue antiemetic use, and nausea and vomiting as secondary outcomes at specified time points.. We included 14 RCTs (1917 participants) from high-, middle- and low-income countries, representing over 24 different cancers. Thirteen studies were in chemotherapy-induced nausea and vomiting. Oral olanzapine was administered during highly emetogenic (HEC) or moderately emetogenic (MEC) chemotherapy (12 studies); chemoradiotherapy (one study); or palliation (one study). Eight studies await classification and 13 are ongoing.The main comparison was olanzapine versus placebo/no treatment. Other comparisons were olanzapine versus NK1 antagonist, prokinetic, 5-HT3 antagonist or dexamethasone.We assessed all but one study as having one or more domains that were at high risk of bias. Eight RCTs with fewer than 50 participants per treatment arm, and 10 RCTs with issues related to blinding, were at high risk of bias. We downgraded GRADE assessments due to imprecision, inconsistency and study limitations.Olanzapine versus placebo/no treatmentPrimary outcomesOlanzapine probably doubles the likelihood of no nausea or vomiting during chemotherapy from 25% to 50% (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.59 to 2.47; 561 participants; 3 studies; solid tumours; HEC or MEC therapy; moderate-quality evidence) when added to standard therapy. Number needed to treat for additional beneficial outcome (NNTB) was 5 (95% CI 3.3 - 6.6).It is uncertain if olanzapine increases the risk of serious adverse events (absolute risk difference 0.7% more, 95% CI 0.2 to 5.2) (RR 2.46, 95% CI 0.48 to 12.55; 7 studies, 889 participants, low-quality evidence).Secondary outcomesFour studies reported patient perception of treatment. One study (48 participants) reported no difference in patient preference. Four reported quality of life but data were insufficient for meta-analysis.Olanzapine may increase other adverse events (RR 1.71, 95% CI 0.99 to 2.96; 332 participants; 4 studies; low-quality evidence) and probably increases somnolence and fatigue compared to no treatment or placebo (RR 2.33, 95% CI 1.30 to 4.18; anticipated absolute risk 8.2% more, 95% CI 1.9 to 18.8; 464 participants; 5 studies; moderate-quality evidence). Olanzapine probably does not affect all-cause attrition (RR 0.99, 95% CI 0.57 to 1.73; 943 participants; 8 studies; I² = 0%). We are uncertain if olanzapine increases attrition due to adverse events (RR 3.00, 95% CI 0.13 to 70.16; 422 participants; 6 studies). No participants withdrew due to lack of efficacy.We are uncertain if olanzapine reduces breakthrough nau. There is moderate-quality evidence that oral olanzapine probably increases the likelihood of not being nauseous or vomiting during chemotherapy from 25% to 50% in adults with solid tumours, in addition to standard therapy, compared to placebo or no treatment. There is uncertainty whether it increases serious adverse events. It may increase the likelihood of other adverse events, probably increasing somnolence and fatigue. There is uncertainty about relative benefits and harms of 5 mg versus 10 mg.We identified only RCTs describing oral administration. The findings of this review cannot be extrapolated to provide evidence about the efficacy and safety of any injectable form (intravenous, intramuscular or subcutaneous) of olanzapine.

Topics: Adult; Antiemetics; Antineoplastic Agents; Benzodiazepines; Chemoradiotherapy; Dexamethasone; Disorders of Excessive Somnolence; Fatigue; Humans; Metoclopramide; Nausea; Neoplasms; Olanzapine; Quality of Life; Randomized Controlled Trials as Topic; Vomiting

Nausea and vomiting are frequent and fearful issues both of cancer itself and its treatment, resulting in reduced quality of life, hospitalization and unnecessary medical investigations. Unconventionally, the author discusses the treatment-related and non-treatment-related complaints together, so as to give an integrated approach to this problem. Different types of nausea/vomiting and important causes are explained by discussion of the pathophysiology and clinical symptoms. Different classes of antiemetics are detailed, emphasizing the evolving role of olanzapine in the treatment of both the acute and delayed type of chemotherapy-induced nausea/vomiting. It was no aim of this review to detail all aspects of MASCC and ESMO antiemetic guideline issued in 2016, but the main topics are presented together with other antiemetic strategies.. Mind a daganatos betegségnek, mind az onkológiai kezelésnek gyakori, rettegett velejárója a hányinger, ill. a hányás, mely jelentõsen rontja az életminõséget, hospitalizációt és felesleges vizsgálatokat eredményezhet. A szerzõ – rendhagyó módon – együtt tárgyalja a kemo- és sugárterápiához társuló, valamint a betegség elõrehaladott stádiumában jelentkezõ ezen panaszokat, egységes szemléletet kívánva adni a probléma kezeléséhez. A patofiziológiai alapok áttekintése kapcsán bemutatja a hányinger-hányás különbözõ típusait, gyakorlati szempontokat szem elõtt tartó differenciáldiagnosztikáját, majd részletesen bemutatja a különbözõ hányáscsillapító gyógyszercsoportokat. Kiemeli az elmúlt néhány év vizsgálati eredményei alapján az olanzapin meglepõen jó hatékonyságát mind a kemoterápiához társuló akut, mind a késõi típusú hányinger-hányás megelõzésében, ill. kezelésében. Bár nem törekszik a MASCC és ESMO által 2016-ban kibocsátott új antiemetikus vezérelv teljes körû ismertetésére, ennek összefoglaló ajánlása az egyéb eredetû hányinger-hányás csillapítással együtt bemutatásra kerül.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Diagnosis, Differential; Humans; Hungary; Nausea; Neoplasms; Olanzapine; Palliative Care; Prognosis; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vomiting

The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV).. The literature was searched for randomized controlled trials (RCTs) evaluating the efficacy of olanzapine for the prophylaxis of CINV using PubMed, Embase, Central, as well as clinicaltrials.gov for unpublished studies. The endpoints of the study were the number of patients who achieved a complete response (CR; no emesis and no rescue) and no nausea in the acute, delayed and overall phases. Two authors independently selected studies, assessed the risk of bias and extracted data. The included RCTs were analysed using RevMan 5.3 provided by the Cochrane Collaboration.. Ten RCTs were identified for the meta-analysis. Compared with other antiemetic agents, olanzapine significantly improved the CR in the delayed and overall phases, but did not enhance the CR in the acute phase. For the control of CINV, olanzapine was better than and comparable with aprepitant in the acute phase and delayed phase, respectively. Compared with placebo, treatment with 5 mg and 10 mg olanzapine exhibited similar efficacy in terms of the CR in the delayed and overall phases.. Olanzapine is an excellent alternative for the prophylaxis of CINV. Olanzapine 5 mg per day should be recommended as the initial dose because of equivalent efficacy to a 10 mg dose but a lower potential risk of side effects. Further studies are needed to explore the optimal combination of medicines.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Humans; Morpholines; Nausea; Neoplasms; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting

The purpose of review is to critically present the evidence supporting the use of olanzapine, an atypical antipsychotic, as an antiemetic for cancer and chemotherapy-induced nausea and vomiting (CINV).. Two phase III clinical studies demonstrated superior efficacy of olanzapine in comparison with the neurokinin-1 receptor antagonists (NK1RA) for substance P (aprepitant, fosaprepitant) in the prevention of nausea after highly emetogenic chemotherapy. Olanzapine is inexpensive and the replacement of NK1RA with olanzapine can reduce the costs of the prevention of CINV. The addition of olanzapine to aprepitant-containing combination regimens for the prevention of CINV was also investigated, and has the potential to further improve the prevention of CINV after highly emetogenic chemotherapy or moderately emetogenic chemotherapy, without substantial increase in costs. In the treatment of uncontrolled ('breakthrough') CINV, olanzapine was more effective than metoclopramide. Existing clinical data also support the use of olanzapine to relieve a cluster of gastrointestinal symptoms in patients with advanced cancer (chronic nausea, vomiting, and anorexia). When used in cancer patients, olanzapine is well tolerated, with sedation being the major dose-limiting side effect.. Existing data from clinical trials justify further research of the role of olanzapine in the prevention of CINV. Olanzapine may be used instead of or in addition to NK1RA in the preventive antiemetic regimens. Olanzapine-containing preventive regimens may provide better nausea control after chemotherapy. When used instead of NK1RA it may also provide substantial reduction in costs of CINV prevention. In patients with advanced cancer, olanzapine was effective against a cluster of gastrointestinal symptoms (nausea, vomiting, and anorexia). The use of olanzapine as an antiemetic for CINV, or to relieve nausea, vomiting, and anorexia in palliative care is currently off-label.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Humans; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Substance P; Vomiting

This review provides background information on chemotherapy-induced nausea and vomiting (CINV) classification and pathophysiology and reviews various antiemetic agents for CINV prophylaxis, including corticosteroids, serotonin receptor antagonists (5-HT3 RAs), tachykinin NK1 receptor antagonists (NK1 RAs), and olanzapine. Other less commonly used agents are briefly discussed. Practical considerations are reviewed as well, including emetogenicity of chemotherapeutic regimens, patient-specific risk factors for CINV, principles of CINV management, health economics outcome research, and quality of life. Available data on the newly FDA-approved antiemetic combination netupitant/palonosetron (NEPA) is also reviewed. Prevention of CINV is an important goal in managing patients with cancer and is especially difficult with respect to nausea and delayed CINV. Corticosteroids are a mainstay of CINV prophylaxis and are usually given in combination with other therapies. The 5-HT3 RA palonosetron has shown increased efficacy over other agents in the same class for prevention of delayed emesis with moderately emetogenic chemotherapy and NK1 RAs improve emesis prevention in combination with 5-HT3 RAs and dexamethasone. Olanzapine has shown efficacy for CINV prophylaxis and the treatment of breakthrough CINV. The new combination therapy, NEPA, has been shown to be efficacious for the prevention of acute, delayed, and overall CINV. Risk factors that have been identified for CINV include gender, age, and alcohol intake. It is important to assess the emetogenicity of chemotherapy regimens as well as the potential impact of patient risk factors in order to provide adequate prophylaxis. Acute and delayed CINV are severe, burdensome side effects of chemotherapy; however, new data on prevention and the discovery of new agents can further improve CINV control.

Topics: Adrenal Cortex Hormones; Antiemetics; Antineoplastic Agents; Benzodiazepines; Drug Combinations; Drug Therapy, Combination; Humans; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Quality of Life; Risk Factors; Serotonin Antagonists; Vomiting

Nausea and vomiting are common adverse events in chemotherapy. In spite of the serious effects on the quality of life and further treatment, they remain overlooked by physicians, and no standard treatment has been developed. Neurokinin-1 (NK-1) receptor antagonists and palonosetron are the major agents in the standard regimen for treating moderately and highly emetogenic chemotherapy-induced nausea and vomiting (CINV). However, NK-1 receptor antagonists first became commercially available at the end of 2013 and palonosetron has not been extensively applied in China. Olanzapine was recommended as a therapy for moderate and severe CINV in antiemesis-clinical practice guidelines in oncology in 2014 for the first time. It is an atypical antipsychotic agent, which can block multiple receptors on neurotransmitters. During more than 10 years, olanzapine has demonstrated significant effects in preventing CINV and treating breakthrough and refractor CINV, which was observed in case reports, precise retrospective studies, and phase I, II and III clinical trials, with no grade 3 to 4 adverse events. In particular, it is superior to aprepitant and dexamethasone in delayed nausea and vomiting. Therefore, this compound is worthy of further investigation.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Emetics; Humans; Isoquinolines; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quinuclidines; Vomiting

Olanzapine is an atypical antipsychotic agent of the thienobenzodiazepine class. Olanzapine blocks multiple neurotransmitter receptors, including dopaminergic (D(1), D(2), D(3), and D(4)), serotonergic (5-hydroxytryptamine 2A [5-HT(2A)], 5-HT(2C), 5-HT(3), and 5-HT(6)), adrenergic (α(1)), histaminic (H(1)), and muscarinic (M(1), M(2), M(3), and M(4)) receptors. Olanzapine has a high affinity for the 5HT(2A) receptor, which is up to 5 times greater than the dopamine receptor, resulting in less propensity to the development of extrapyramidal side effects. The affinity of olanzapine for multiple receptors has lead to the identification of olanzapine as an important agent in the treatment of delirium, nausea, and vomiting. Olanzapine has been demonstrated to have opioid-sparing properties. Olanzapine is principally metabolized by glucuronidation, with a smaller metabolic contribution from the cytochrome oxidase system. Adverse effects of olanzapine include somnolence, postural hypotension, constipation, dizziness, restlessness, and weight gain. The purpose of this article is to outline the pharmacodynamics, pharmacology, and evidence for the use of olanzapine in palliative care.

Topics: Benzodiazepines; Clinical Trials as Topic; Critical Illness; Dementia; Drug Interactions; Humans; Nausea; Neoplasms; Olanzapine; Pain Management; Palliative Care; Selective Serotonin Reuptake Inhibitors; Vomiting

Nausea and vomiting are often encountered in palliative care patients. Multiple medications are available to provide relief. However, several drug combinations are usually used to treat emesis. Current research has identified several receptors that trigger nausea and vomiting, hence the difficulty of using only 1 medication to provide relief. Olanzapine is a drug approved for treatment of schizophrenia and mania. It blocks multiple neurotransmitters dopaminergic, serotonergic, adrenergic (alpha(1)), histaminergic, and muscarinic receptors. Most of these receptors are also involved in causing emesis. Studies have shown that olanzapine could be used to treat nausea and vomiting with promising results.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Evidence-Based Medicine; Humans; Nausea; Neoplasms; Olanzapine; Quality of Life; Treatment Outcome; Vomiting

Advanced cancer patients are polysymptomatic and often receive multiple medications for symptom relief. Common symptoms include anorexia, weight loss, delirium and depression. Olanzapine and mirtazapine may have several advantages over older agents despite increased acquisition costs. Both medications can treat several symptoms with a low risk for drug-drug interactions and with only once- or twice-daily dosing. Drug side effects are low, compared with more conventionally used agents. The pharmacokinetics and pharmacodynamics of both agents are unique and explain many of the benefits. More research and clinical experience will be necessary to define their role in the palliation of advanced cancer.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Drug Interactions; Humans; Mianserin; Mirtazapine; Neoplasms; Olanzapine; Palliative Care; Pirenzepine

Clinical observations of cancer patients treated with selinexor have reported high incidence of nausea and anorexia. The study objective was to investigate the adoption of prophylactic olanzapine for the prevention of nausea, vomiting and anorexia in cancer patients receiving selinexor and standard chemotherapy.. We retrospectively reviewed supportive care interventions in patients receiving selinexor and recorded frequency of adverse events (NCI-CTAE). Association between categorical variables were analyzed using Fisher's exact tests; repeated measures analysis was performed to assess weight changes over time.. Of 124 evaluable patients, 83 (66.9%) were female, 93 were white (75.0%), and the most common cancer was ovarian (N = 30, 24.2%). One hundred and four patients (83.9%) received olanzapine, of which 93 (89.4%) were prophylactically treated, the majority (86.5%) receiving low 2.5 mg daily dose. Other anti-emetics included ondansetron in 90 patients (72.6%), dexamethasone prescribed in 50 patients (40.3%) and metoclopramide in 49 patients (39.5%), while aprepitant/fosaprepitant (N = 2, 1.6%) were prescribed infrequently. Cancer patients receiving prophylactic olanzapine (N = 93) compared to patients who never received olanzapine (N = 20) had more Grade 1 + anorexia (31.2% vs 20.0%), less nausea (53.8% vs 70.0%), less vomiting (33.3% vs 40.0%), and increased hyperglycemia (29.0% vs 10.0%), but differences were non-statistically significant. In addition, there was minimal weight loss over time in both groups and no statistically significant differences in weight loss between groups.. Prophylactic olanzapine decreased nausea, vomiting and maintained weight over 3 months but did not prevent anorexia in patients receiving selinexor and chemotherapy. Low dose olanzapine was well tolerated but associated with hyperglycemia.

Topics: Adult; Aged; Anorexia; Antiemetics; Female; Humans; Hydrazines; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Triazoles; Vomiting; Young Adult

In this trial, we evaluated the safety and efficacy of olanzapine in children receiving highly emetogenic chemotherapy.. In this study, patients aged 3 to 18 years were randomly assigned to either the olanzapine group or the placebo group. All patients received intravenous ondansetron and dexamethasone 30 minutes before highly emetogenic chemotherapy, followed by oral ondansetron for 48 hours. Participants in the olanzapine group received olanzapine once daily on days 1 and 2, while those in the control group received a placebo in the same dosage and schedule. The primary objective was: (a) to compare the complete control rates of vomiting in the delayed phase and (b) to compare the complete control rates of vomiting in acute and overall phases. The secondary objective was to evaluate the safety of olanzapine and the need for rescue medications.. A total of 128 patients were randomly assigned either to the olanzapine group (n=63) or the control group (n=65). Complete control of vomiting between olanzapine and placebo group was 73% versus 48% ( P =0.005) in the delayed phase, 60% versus 54% ( P =0.46) in the acute phase, and 48% versus 34% ( P =0.117) in the overall phase, respectively. Grades 1 and 2 sedation was greater in the olanzapine group (46% vs. 14%; P <0.001). A significantly higher proportion of patients in the placebo group required rescue medications for vomiting compared with in the olanzapine group ( P =0.025).. Olanzapine significantly improved complete control of vomiting in the delayed phase. A considerably lesser proportion of patients in the olanzapine group needed rescue medications.

Topics: Antiemetics; Antineoplastic Agents; Child; Dexamethasone; Double-Blind Method; Humans; Nausea; Neoplasms; Olanzapine; Ondansetron; Vomiting

Lay abstract Methods to prevent chemotherapy-induced nausea and vomiting (CINV) are often not sufficient for patients. Olanzapine, along with other similar drugs (antiemetics), improved control but is often sedating. In this study, a lower dose of olanzapine was compared with the conventional dose. Patients on cancer chemotherapy, which has high occurrence of nausea and vomiting, were given either the low dose or the conventional dose of olanzapine for 3 days, in addition to some other antiemetic agents. Control of nausea and vomiting was reasonably achieved with both doses of olanzapine. The lower dose was significantly less sedating. There were no serious side effects with either doses.

Topics: Anti-Inflammatory Agents; Antiemetics; Antineoplastic Agents; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Prospective Studies; Quality of Life; Vomiting

We assessed the efficacy of aprepitant (APR) or 10 or 5 mg OLN (OLN10 or OLN5) plus ondansetron and dexamethasone for chemotherapy-induced nausea/vomiting (CINV) prophylaxis in patients receiving high-emetogenic chemotherapy (HEC).. Patients who received doxorubicin + cyclophosphamide or cisplatin were given intravenous ondansetron and dexamethasone prior to chemotherapy and oral dexamethasone on days 2-4 and randomized 1:1:1 to receive APR125 on day 1 and APR80 on days 2-3 or OLN10 or OLN5 on days 1-4. Matched placebo controls were used. The primary endpoint was no nausea in ≤ 120 h. Secondary endpoints included CINV severity, complete response (CR) rate, adverse effects (AE), and quality of life.. Of 141 patients, 104 received AC and 37 received cisplatin. The no-nausea rates were 33% (APR), 43.2% (OLN10; p = 0.24), and 37% (OLN5; p = 0.87). Grades 2-4 nausea were experienced by fewer patients for OLN10 than for APR (24-120 h, 8.7% vs. 27.7%, respectively; p = 0.02; overall period, 19.6% vs. 40.4%, respectively; p = 0.03). The median visual analog scale nausea score from 24 to 120 h was significantly lower for OLN10 (2.3) than for APR (1.2, p = 0.03). The degrees of vomiting, CR, and AE were similar between the APR and OLN10 groups. CINV was similar between the OLN5 and APR groups.. Nausea was less severe for OLN10 than for APR in patients receiving HEC, but other measures were similar. CINV prevention efficacy was comparable between OLN5 and APR.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Chemoprevention; Cisplatin; Cyclophosphamide; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Doxorubicin; Drug Therapy, Combination; Emetics; Female; Humans; Induction Chemotherapy; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Placebos; Quality of Life; Treatment Outcome; Vomiting; Young Adult

Treatment of delirium often includes haloperidol. Second-generation antipsychotics like olanzapine have emerged as an alternative with possibly fewer side effects. The aim of this multicenter, phase III, randomized clinical trial was to compare the efficacy and tolerability of olanzapine with haloperidol for the treatment of delirium in hospitalized patients with advanced cancer.. Eligible adult patients (≥18 years) with advanced cancer and delirium (Delirium Rating Scale-Revised-98 [DRS-R-98] total score ≥17.75) were randomized 1:1 to receive either haloperidol or olanzapine (age-adjusted, titratable doses). Primary endpoint was delirium response rate (DRR), defined as number of patients with DRS-R-98 severity score <15.25 and ≥4.5 points reduction. Secondary endpoints included time to response (TTR), tolerability, and delirium-related distress.. Between January 2011 and June 2016, 98 patients were included in the intention-to-treat analysis. DRR was 45% (95% confidence interval [CI], 31-59) for olanzapine and 57% (95% CI, 43-71) for haloperidol (Δ DRR -12%; odds ratio [OR], 0.61; 95% CI, 0.2-1.4; p = .23). Mean TTR was 4.5 days (95% CI, 3.2-5.9 days) for olanzapine and 2.8 days (95% CI, 1.9-3.7 days; p = .18) for haloperidol. Grade ≥3 treatment-related adverse events occurred in 5 patients (10.2%) and 10 patients (20.4%) in the olanzapine and haloperidol arm, respectively. Distress rates were similar in both groups. The study was terminated early because of futility.. Delirium treatment with olanzapine in hospitalized patients with advanced cancer did not result in improvement of DRR or TTR compared with haloperidol. Clinical trial identification number. NCT01539733. Dutch Trial Register. NTR2559.. Guidelines recommend that pharmacological interventions for delirium treatment in adults with cancer should be limited to patients who have distressing delirium symptoms. It was suggested that atypical antipsychotics, such as olanzapine, outperform haloperidol in efficacy and safety. However, collective data comparing the efficacy and safety of typical versus atypical antipsychotics in patients with cancer are limited. If targeted and judicious use of antipsychotics is considered for the treatment of delirium in patients with advanced cancer, this study demonstrated that there was no statistically significant difference in response to haloperidol or olanzapine. Olanzapine showed an overall better safety profile compared with haloperidol, although this difference was not statistically significant.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Haloperidol; Humans; Neoplasms; Olanzapine; Risperidone

Nausea and vomiting, unrelated to chemotherapy, can be substantial symptoms in patients with advanced cancer.. To evaluate the utility of olanzapine for treating chronic nausea/vomiting, unrelated to chemotherapy, in patients with advanced cancer.. This study is a double-line, placebo-controlled, randomized clinical trial conducted from July 2017 through April 2019, with analysis conducted in 2019. Eligible participants were outpatients with advanced cancer who had persistent nausea/vomiting without having had chemotherapy or radiotherapy in the prior 14 days. Chronic nausea was present for at least 1 week (worst daily nausea numeric rating scores needed to be greater than 3 on a 0-10 scale).. Patients received olanzapine (5 mg) or a placebo, orally, daily for 7 days.. Patient-reported outcomes were used for study end points. Data were collected at baseline and daily for 7 more days. The primary study end point (the change in nausea numeric rating scores from baseline to the last treatment day) and the study hypothesis were both identified prior to data collection.. A total of 30 patients (15 per arm) were enrolled; these included 16 women and 14 men who had a mean (range) age of 63 (39-79) years. Baseline median nausea scores, in all patients, were 9 out of 10 (range, 8-10). After 1 day and 1 week, the median nausea scores in the placebo arm were 9 out of 10 (range, 8-10) on both days, compared with the olanzapine arm scores of 2 out of 10 (range, 2-3) after day 1 and 1 out of 10 (range, 0-3) after 1 week. After 1 week of treatment, the reduction in nausea scores in the olanzapine arm was 8 points (95% CI, 7-8) higher than that of the placebo arm. The primary 2-sided end point P value was <.001. Correspondingly, patients in the olanzapine arm reported less emesis, less use of other antiemetic drugs, better appetite, less sedation, less fatigue, and better well-being. One patient, on the placebo, stopped treatment early owing to lack of perceived benefit. No patients receiving olanzapine reported excess sedation or any other adverse event.. Olanzapine, at 5 mg/d, appeared to be effective in controlling nausea and emesis and in improving other symptoms and quality-of-life parameters in the study population.. ClinicalTrials.gov Identifier: NCT03137121.

Topics: Adult; Aged; Antiemetics; Double-Blind Method; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Pilot Projects; Vomiting

Breakthrough chemotherapy-induced vomiting (CIV) is defined as CIV occurring after adequate antiemetic prophylaxis. Olanzapine and metoclopramide are two drugs recommended for the treatment of breakthrough CIV in children, without adequate evidence. We conducted an open-label, single-center, phase 3 randomized controlled trial comparing the safety and efficacy of olanzapine and metoclopramide for treating breakthrough CIV.. Children aged 5-18 years who developed breakthrough CIV after receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy were randomly assigned to the metoclopramide or olanzapine arm. The primary objective of the study was to compare the complete response (CR) rates between patients receiving olanzapine or metoclopramide for treating breakthrough CIV during 72 hours after the administration of the study drug. Secondary objectives were to compare CR rates for nausea and toxicities between the two arms.. Eighty patients were analyzed (39 in the olanzapine arm and 41 in the metoclopramide arm). CR rates were significantly higher in the olanzapine arm compared with the metoclopramide arm for vomiting (72% vs 39%, P = 0.003) and nausea (59% vs 34%, P = 0.026). Seven patients in the metoclopramide arm crossed over to the olanzapine arm and none crossed over in the olanzapine arm (P < 0.001). The mean nausea score in the olanzapine arm was significantly lower than the metoclopramide arm after the initiation of the rescue antiemetic (P = 0.01). Hyperglycemia and drowsiness were more commonly seen in the olanzapine arm.. Olanzapine is superior to metoclopramide for the treatment of breakthrough CIV in children. Drowsiness and hyperglycemia need to be monitored closely in children receiving olanzapine for breakthrough CIV.

Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Male; Metoclopramide; Neoplasms; Olanzapine; Prognosis; Vomiting

The antipsychotic drug olanzapine is effective against chemotherapy-induced nausea and targets multiple receptors known to be involved in the emetic reflex arch. The drug has a mean half-life of 30 h, which allows for a single daily administration and is therefore of interest in patients with advanced cancer suffering from nausea.. To investigate the antiemetic effect and tolerability of olanzapine in patients with advanced cancer not receiving chemotherapy or irradiation.. Patients with advanced cancer (no curable treatment options) with at least "moderate" nausea and/or one emetic episode within the last 24 h were included if they had not received chemotherapy or irradiation (last 2 weeks) and had no reversible causes of nausea/vomiting. Patients were administered 10 mg olanzapine daily for 5 days (the first day subcutaneously and the following 4 days orally). Nausea, vomiting, and adverse effects were assessed daily for 7 days. The primary efficacy parameter was nausea after 24 h.. Forty patients from four centers were included and all evaluable after 24 h. Thirty-six patients experienced some degree of improvement. The mean two-item N/V score (0-100) at baseline was 66 and improved to 21 and 24 after 24 h and 7 days, respectively. During the course of the study, the dose of olanzapine was reduced in three patients due to adverse events. Five patients were withdrawn from the study primarily due to progression of malignant disease or per patient's request.. Olanzapine appears effective and tolerable as an antiemetic in patients with advanced cancer. Future research should examine a lower dose (5 or 2.5 mg), preferably in a randomized controlled trial.

Topics: Adult; Aged; Antiemetics; Antipsychotic Agents; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Vomiting

The purpose of the study was to compare efficacy and toxicity of olanzapine (OLN; a higher-cost drug) and haloperidol (HAL; a lower-cost drug) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC).. In a randomized, phase II trial, patients were randomly assigned to receive either OLN 10 mg orally on days 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg twice daily on days 2 to 4. Both groups received ondansetron 16 mg and dexamethasone 12 mg intravenously on day 1. Patients recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS) and recorded daily episodes of vomiting from day 1 to day 5. The primary end point was complete nausea prevention (CNP; ie, ESAS of 0). Secondary end point was complete emesis prevention (CEP).. Sixty-five patients were randomly assigned, and 64 received their allocated treatment (n = 32 in each arm). There was no difference in CNP during the overall period (days 1 to 5) between OLN and HAL (68.7%. In this study, HAL had comparable efficacy to OLN in the management of CINV, which suggests that it is the higher-value option in patients who receive HEC in resource-scarce countries.

Topics: Administration, Intravenous; Administration, Oral; Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Drug Administration Schedule; Female; Haloperidol; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Random Allocation; Treatment Outcome; Vomiting; Young Adult

The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC).. A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (≥ 50 mg/m. 153 patients were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3-83.8, P = 0.01) in the 10 mg group and 85.7% (80% CI: 79.2-90.7, P < 0.001) in the 5 mg group (P value for H. Both doses of 10 and 5 mg olanzapine provided a significant improvement in delayed emesis. A dose of 5 mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates.. UMIN000014214.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Double-Blind Method; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Neoplasms; Olanzapine; Palonosetron; Quinuclidines; Treatment Outcome; Vomiting

This retrospective review provides preliminary data regarding the safety and efficacy of olanzapine for chemotherapy-induced vomiting (CIV) control in children.. Children <18 years old who received olanzapine for acute chemotherapy-induced nausea and vomiting (CINV) control from December 2010 to August 2013 at four institutions were identified. Patient characteristics, chemotherapy, antiemetic prophylaxis, olanzapine dosing, CIV control, liver function test results and adverse events were abstracted from the health record. Toxicity was graded using CTCAEv4.03.. Sixty children (median age 13.2 years; range: 3.10-17.96) received olanzapine during 158 chemotherapy blocks. Olanzapine was most often (59%) initiated due to a history of poorly controlled CINV. The mean initial olanzapine dose was 0.1 mg/kg/dose (range: 0.026-0.256). Most children who received olanzapine beginning on the first day of the chemotherapy block experienced complete CIV control throughout the acute phase (83/128; 65%). There was no association between the olanzapine dose/kg and complete CIV control (OR 1.01; 95% CI: 0.999-1.020; P = 0.091). Sedation was reported in 7% of chemotherapy blocks and was significantly associated with increasing olanzapine dose (OR: 1.17; 95% CI: 1.08-1.27; P = 0.0001). Of the 25 chemotherapy blocks where ALT and/or AST were reported more than once, grade 1-3 elevations were observed in five. The mean weight change in 31 children who received olanzapine during more than one chemotherapy block was 0% (range: -22 to +18).. Olanzapine may be an important option to improve CIV control in children. Prospective controlled evaluation of olanzapine for CINV prophylaxis in children is warranted.

Topics: Acute Disease; Adolescent; Antiemetics; Antineoplastic Agents; Benzodiazepines; Child; Child, Preschool; Female; Humans; Male; Neoplasms; Olanzapine; Retrospective Studies; Vomiting

Olanzapine is used for treatment of psychiatric conditions but causes substantial weight gain. This study assessed safety, efficacy, and changes in metabolic cytokines associated with olanzapine administration in patients with cachexia due to advanced cancer.. Patients with cancer-related cachexia were treated with olanzapine (doses ranging from 2.5 to 20 mg daily by mouth). Patients also received anti-neoplastic treatments. Serum samples were collected at baseline and after weeks 1, 2, 4, and 8 for analysis of levels of leptin, growth hormone, ghrelin, and interleukin-6 (IL-6).. Of the 39 participants, 31 were evaluable for weight change (N = 6 excluded for new ascites; N = 2, incomplete body weight of data). Toxicities related to olanzapine were somnolence (n = 1), pancreatitis (n = 1), extrapyramidal symptoms (n = 1), and nausea/vomiting (n = 1) (all grade 2). The recommended dose of Olanzapine is 20 mg PO daily for cancer patients (same as FDA approved dose for psychiatric conditions). Samples from 29 patients were eligible for analysis of serum cytokine levels. Mean values of leptin, ghrelin, and growth hormone did not change on treatment, though IL-6 levels increased, perhaps due to tumor progression. There was no association between changes in cytokines and weight. The mean change in slope of weight loss before versus after therapy was 0.24 (95 % CI, -0.08, 0.56; p = 0.13) indicating a trend, albeit not reaching statistical significance, toward attenuation of weight loss.. Changes in metabolic cytokines and body weight did not correlate. Treatment with olanzapine had only a modest effect in altering the trajectory of weight loss.

Topics: Adult; Aged; Benzodiazepines; Body Weight; Cachexia; Cytokines; Dose-Response Relationship, Drug; Female; Ghrelin; Humans; Interleukin-6; Leptin; Male; Middle Aged; Neoplasms; Olanzapine; Weight Gain; Weight Loss

To evaluate safety and efficacy of olanzapine for breakthrough emesis in addition to standard antiemetic regimen in cancer patients receiving highly emetogenic chemotherapy.. A phase II prospective open label clinical trial was conducted in tertiary care based hospital. Forty-six cancer patients diagnosed with solid tumors were enrolled to receive at least one cycle of highly emetogenic chemotherapy (HEC) every two to four weeks. Each patient was provided standard antiemetic consisting of the generic form of ondansetron plus corticosteroids and metoclopramide according to clinical practice guideline. Olanzapine was administered as 5 mg orally every 12 hours for two doses in patients experiencing breakthrough emesis for at least one episode despite standard prevention. The efficacy and tolerability were evaluated every six hours for 24 hours (utilizing Index of Nausea, Vomiting and Retching: INVR tool).. Of 46 evaluable patients receiving HEC and additional olanzapine between September 2009 and July 2010, the complete response of breakthrough emesis, retching, and nausea control among patients were 60.9%, 71.7%, and 50.0%, respectively. Adverse events reported were mild and tolerable including dizziness, fatigue, and dyspepsia.. Olanzapine is considered to be safe and effective treatment of breakthrough vomiting in cancer patients undergoing highly emetogenic chemotherapy in the present study.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Prospective Studies; Treatment Outcome; Vomiting

Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis.. A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥ 70 mg/m2 or doxorubicin, ≥ 50 mg/m2 and cyclophosphamide, ≥ 600 mg/m2), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38-79; 43% women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable.. During the 72-h observation period, 39 out of 56 (70%) patients receiving olanzapine had no emesis compared to 16 out of 52 (31%) patients with no emesis for patients receiving metoclopramide (p < 0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68% (38 of 56), and metoclopramide, 23% (12 of 52) (p < 0.01). There were no grade 3 or 4 toxicities.. Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Female; Humans; Isoquinolines; Male; Metoclopramide; Middle Aged; Morpholines; Nausea; Neoplasms; Olanzapine; Palonosetron; Quinuclidines; Vomiting

This study was designed to mainly evaluate the activity and safety of olanzapine compared with 5-hydroxytryptamine 3(5-HT3) receptor antagonists for prevention of chemotherapy-induced nausea and vomiting(CINV) in patients receiving highly or moderately emetogenic chemotherapy (HEC or MEC). The second goal was to evaluate the impact of olanzapine on quality of life (QoL) of cancer patients during the period of chemotherapy.. 229 patients receiving highly or moderately emetogenic chemotherapy were randomly assigned to the test group [olanzapine(O) 10 mg p.o. plus azasetron (A) 10 mg i.v. and dexamethasone (D) 10 mg i.v. on day 1; O 10 mg once a day on days 2-5] or the control group (A 10 mg i.v. and D 10 mg i.v. on day 1; D 10 mg i.v. once a day on days 2-5). All the patients filled the observation table of CINV once a day on days 1-5, patients were instructed to fill the EORTC QLQ-C30 QoL observation table on day 0 and day 6. The primary endpoint was the complete response (CR) (without nausea and vomiting, no rescue therapy) for the acute period (24 h postchemotherapy), delayed period (days 2-5 postchemotherapy), the whole period (days 1-5 postchemotherapy). The second endpoint was QoL during chemotherapy administration, drug safety and toxicity.. 229 patients were evaluable for efficacy. Compared with control group, complete response for acute nausea and vomiting in test group had no difference (p > 0.05), complete response for delayed nausea and vomiting in patients with highly emetogenic chemotherapy respectively improved 39.21% (69.64% versus 30.43%, p < 0.05), 22.05% (78.57% versus 56.52%, p < 0.05), complete response for delayed nausea and vomiting in patients with moderately emetogenic chemotherapy respectively improved 25.01% (83.07% versus 58.06%, p < 0.05), 13.43% (89.23% versus 75.80%, p < 0.05), complete response for the whole period of nausea and vomiting in patients with highly emetogenic chemotherapy respectively improved 41.38% (69.64% versus 28.26%, p < 0.05), 22.05% (78.57% versus 56.52%, p < 0.05), complete response for the whole period of nausea and vomiting in patients with moderately emetogenic chemotherapy respectively improved 26.62% (83.07% versus 56.45%, p < 0.05), 13.43% (89.23% versus 75.80%, p < 0.05). 214 of 299 patients were evaluable for QoL. Comparing test group with control group in QoL evolution, significant differences were seen in global health status, emotional functioning, social functioning, fatigue, nausea and vomiting, insomnia and appetite loss evolution in favour of the test group (p < 0.01). Both treatments were well tolerated.. Olanzapine can improve the complete response of delayed nausea and vomiting in patients receiving the highly or moderately emetogenic chemotherapy comparing with the standard therapy of antiemesis, as well as improve the QoL of the cancer patients during chemotherapy administration. Olanzapine is a safe and efficient drug for prevention of CINV.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Benzodiazepines; Bridged Bicyclo Compounds, Heterocyclic; Dexamethasone; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Oxazines; Quality of Life; Serotonin 5-HT3 Receptor Antagonists; Vomiting

The purpose of this study is to determine the control of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC) with the combined use of palonosetron and olanzapine, and dexamethasone with the dexamethasone given on day 1 only.. Forty chemotherapy-naive patients received on the day of chemotherapy, day 1, an anti-emetic regimen consisting of dexamethasone, palonosetron, and olanzapine. Patients continued olanzapine for days 2-4 after chemotherapy administration. Patients recorded daily episodes of emesis, daily symptoms utilizing the M.D. Anderson Symptom Inventory, and the utilization of rescue therapy.. For the first cycle of chemotherapy, the complete response (no emesis, no rescue) for the acute period (24 h post-chemotherapy) was 100%, the delayed period (days 2-5 post-chemotherapy) 75%, and the overall period (0 120 h post-chemotherapy) 75% in 8 patients receiving HEC and was 97, 75, and 72% in 32 patients receiving MEC. Patients with no nausea for the acute period was 100%, the delayed period 50%, and the overall period 50% in 8 patients receiving HEC and was 100, 78, and 78% in 32 patients receiving MEC.. The complete response and control of nausea in subsequent cycles of chemotherapy were not significantly different from cycle one.. Olanzapine combined with a single dose of dexamethasone and a single dose of palonosetron was very effective in controlling acute and delayed CINV in patients receiving both HEC and MEC.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Benzodiazepines; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Outcome Assessment, Health Care; Palonosetron; Quinuclidines; United States; Vomiting

Chemotherapy-induced delayed emesis (DE) can affect up to 50% to 70% of patients receiving moderately and highly emetogenic chemotherapy, although rates are improving. DE most commonly occurs within the first 24 to 48 hours of chemotherapy administration and can persist for 2 to 5 days. Olanzapine, due to its activity at multiple dopaminergic, serotonergic, muscarinic, and histaminic receptor sites, has potential as antiemetic therapy. A phase I study was designed with olanzapine, using a four-cohort dose escalation of 3 to 6 patients per cohort, for the prevention of DE in cancer patients receiving their first cycle of chemotherapy consisting of cyclophosphamide, doxorubicin, platinum, and/or irinotecan. All patients received standard premedication. Olanzapine was administered on days -2 and -1 prior to chemotherapy and continued for 8 days (days 0-7). Episodes of vomiting as well as daily measurements of nausea, sedation, and toxicity were monitored at each dose level. Fifteen patients completed the protocol. No grade 4 toxicities were seen, and three patients experienced a dose-limiting toxicity (grade 3) of a depressed level of consciousness during the study. The maximum tolerated dose appeared to be 5 mg (for days -2 and -1) and 10 mg (for days 0-7). Four of six patients receiving highly emetogenic chemotherapy (cisplatin, > or = 70 mg/m2) and nine of nine patients receiving moderately emetogenic chemotherapy (doxorubicin, > or = 50 mg/m2) had complete control (no vomiting episodes) of DE. Therefore, olanzapine may be an effective agent for the prevention of chemotherapy-induced DE. A phase II trial is underway.

Topics: Adult; Aged; Anorexia; Antiemetics; Antineoplastic Agents; Benzodiazepines; Camptothecin; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Mood Disorders; Nausea; Neoplasms; Olanzapine; Organoplatinum Compounds; Time Factors; Treatment Outcome; Vomiting

In cancer patients, cognitive impairment, psychological distress, and anxiety may accompany and aggravate pain. Neuroleptics are frequently used to control these symptoms and may be used to treat pain that has been unresponsive to more conventional approaches. Because of prominent side effects of traditional neuroleptics and conflicting data regarding their analgesic efficacy, their use in the treatment of pain remains controversial. Olanzapine, an atypical neuroleptic, might offer advantages because of its safer side effect profile. It has also been shown to have an independent antinociceptive activity in animals. The use of olanzapine in the management of cancer pain has not been previously described. We prospectively collected the data on 8 cancer patients with severe pain, uncontrolled in spite of aggressive opioid titration, who received olanzapine to treat severe anxiety and mild cognitive impairment. Patients did not meet criteria for delirium and their cognitive impairment was defined as cognitive disorder not otherwise specified (NOS) according to DSM-IV. Patients received 2.5 to 7.5 mg of olanzapine daily. In all patients, opioid requirements had escalated rapidly prior to starting olanzapine. Levels of pain, sedation, and opioid use were measured 2 days before and 2 days after olanzapine was started. Cognitive state was assessed daily. All 8 patients had marked reduction of the daily pain scores. The average daily opioid use decreased significantly in all patients. Cognitive impairment and anxiety resolved within 24 hours of initiating olanzapine. In these 8 patients, decreased pain scores and opioid requirements may have resulted from improvement in cognitive function and the known anxiolytic effect of olanzapine. Other mechanisms may include independent or adjuvant analgesic effects of olanzapine. We conclude that olanzapine may be useful in the treatment of patients with uncontrolled cancer pain associated with cognitive impairment or anxiety. Further studies to evaluate possible analgesic effect of olanzapine are needed.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Neoplasms; Olanzapine; Pain; Pain Measurement; Pirenzepine; Prospective Studies

Topics: Breast Neoplasms; Cachexia; Female; Home Care Services; Hospice Care; Hospices; Humans; Neoplasms; Olanzapine

Topics: Analgesics, Opioid; Humans; Neoplasms; Olanzapine; Opioid-Related Disorders; Palliative Care

Atypical neuroleptics such as olanzapine are indicated for the treatment of various psychiatric disorders and have been used in the palliative care setting also for several clinical indications. Peripheral and facial edema are a rare side effect of the treatment with olanzapine. We report a case of an advanced cancer patient cared receiving palliative care who developed severe facial edema after initiating a low dose of olanzapine in monotherapy.. A patient with advanced cancer who presented with severe facial edema after initiating olanzapine for the treatment of her opioid use disorder.. After excluding other differential diagnosis for facial edema, olanzapine was discontinued with complete resolution of the edema.. To the best of our knowledge, this is the first case reporting facial edema due to olanzapine treatment in a patient with advanced cancer. Our report will help clinicians recognize the possible role of olanzapine in cases of rapid onset of facial edema, allowing its rapid resolution.

Topics: Antipsychotic Agents; Benzodiazepines; Drug-Related Side Effects and Adverse Reactions; Edema; Female; Humans; Neoplasms; Olanzapine; Palliative Care

Olanzapine is an atypical antipsychotic and is widely used for prophylaxis of chemotherapy-induced nausea and vomiting in cancer patients. Previous studies have suggested its potential efficacy for the relief of various symptoms in cancer patients, especially gastrointestinal and psychiatric symptoms. We retrospectively reviewed the prescription of olanzapine to cancer patients at our hospital. Between 2008 and 2020, olanzapine was prescribed to 41 patients for relief of symptoms associated with cancer other than prophylaxis of chemotherapy-induced nausea and vomiting. Of those patients, symptom relief was seen in 53.7%. Notably, olanzapine was effective in 13 of 14 patients with chemotherapy-induced nausea and vomiting refractory to guideline-recommended prophylaxis. Of 16 patients in whom this symptom was not relieved by olanzapine, 13 (81.3%) continued taking olanzapine even after it was judged ineffective. No treatment-related adverse events were seen in this study. Our observation implies good efficacy of olanzapine for refractory chemotherapy-induced nausea and vomiting and a tendency to continue olanzapine even in those for whom it was ineffective.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Humans; Nausea; Neoplasms; Olanzapine; Retrospective Studies; Vomiting

Topics: Adolescent; Antiemetics; Child; Gastrointestinal Agents; Humans; Nausea; Neoplasms; Olanzapine; Vomiting

Domperidone, ondansetron and olanzapine can prolong the QT interval. The clinical use of combinations of these drugs is not uncommon. Our study aimed to determine the presence of any QTc prolonging effect of the combination when used as antiemetic in patients receiving cancer chemotherapy. We carried out a prospective, observational study of patients with malignancy who were to receive domperidone, ondansetron and olanzapine-containing antiemetic regimen. Electrocardiograms were recorded before and during the administration of antiemetics, for three consecutive days. A blinded assessor determined the QTc interval using Bazett and Fridericia formulae. Thirty-six patients completed the study; 23 (63.9%) were females. There was a statistically significant change in QTc with time (Fridericia, χ

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Domperidone; Drug Combinations; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Prospective Studies; Single-Blind Method; Young Adult

To examine the safety, effectiveness, and patient-perceived benefit of treatment with olanzapine for nausea and vomiting (N/V) in patients with advanced cancer.. We conducted a multicenter prospective observational study in a tertiary care setting (Trial registration number: UMIN000020493, date of registration: 2016/1/12). We measured the following: average nausea in the last 24 h using a Numeric Rating Scale (NRS: range 0-10) at baseline and day 2, patient-perceived treatment benefit (based on a 5-point verbal scale), and adverse events (AEs; using the Common Terminology Criteria for Adverse Events version 4).. The 85 participants (45% men) had a mean age of 58.7±15.8 years. Major causes of N/V were opioids (44%) and chemotherapy (34%). All patients received a daily dose of olanzapine of 5 mg or less as first-line treatment (N=35) or second- or later-line treatment (N=50). Nausea NRS decreased from 6.1±2.2 to 1.8±2.0 (differences: -4.3, 95% CI -3.7 to -4.9, p<0.001). The proportion of patients who did not experience vomiting episodes in the last 24 h increased from 40-89%. Mean decrease in nausea NRS by patient-perceived treatment benefit were as follows: -0.8 for "none" (n=4, 5%); -2.8 for "slight" (n=17, 20%); -3.3 for "moderate" (n=14, 16%); -4.7 for "lots" (n=25, 29%); and -6.1 for "complete" (n=25, 29%; p-for-trend<0.001). The most prevalent AE was somnolence (n=15, 18%).. Short-term and relatively low-dose olanzapine treatment was effective for multifactorial N/V. Confirmatory studies with longer observation periods are needed to clarify the duration of the effect and adverse events.

Topics: Adult; Aged; Antiemetics; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Palliative Care; Referral and Consultation; Vomiting

Olanzapine is effective for schizophrenia management; however, it is contraindicated in diabetes patients. In addition, olanzapine is useful for treating nausea and vomiting, such as in the case of chemotherapy-induced nausea and vomiting (CINV). Therefore, we hypothesized that the contraindicated prescription of olanzapine likely occurs among cancer patients with diabetes, especially by non-psychiatric physicians. Hence, we conducted a nationwide survey to elucidate the situation of such contraindicated prescriptions and the associated risk factors. We extracted the data of patients who were newly prescribed olanzapine between April 2015 and March 2017 from the health insurance claims database developed by JMDC, Inc., Tokyo. The patients who were prescribed contraindicated olanzapine were defined as those who were prescribed olanzapine after a diagnosis of diabetes and diabetes drug prescription. In all, the data of 7181 patients were analyzed. We evaluated the proportion of diabetes patients who were prescribed contraindicated olanzapine from among those who were prescribed olanzapine. Furthermore, we investigated the background of patients who were prescribed olanzapine for information such as olanzapine prescribers and history of cancer chemotherapy. In all, 100 diabetes patients (1.39%) were prescribed olanzapine. In these patients, the frequency of olanzapine prescription was higher by non-psychiatry/neurology physicians than by psychiatry/neurology physicians (3.25 and 0.85%, respectively). Additionally, all olanzapine prescriptions in cancer chemotherapy-treated diabetes patients were issued by non-psychiatry/neurology physicians. Thus, our study revealed there were diabetes patients who were prescribed olanzapine. Additionally, olanzapine for CINV management was more likely to be a contraindicated prescription.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antipsychotic Agents; Contraindications, Drug; Databases, Factual; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Japan; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Risk Factors; Schizophrenia; Vomiting

Topics: Antiemetics; Humans; Male; Metoclopramide; Nausea; Neoplasms; Olanzapine; Vomiting

Topics: Antiemetics; Double-Blind Method; Humans; Metoclopramide; Nausea; Neoplasms; Olanzapine; Vomiting

Topics: Humans; Nausea; Neoplasms; Olanzapine

The efficacy of olanzapine (mean dose 0.09 mg/kg/dose) was evaluated in 31 children 2-18 years of age, for chemotherapy induced breakthrough vomiting. Among 42 chemotherapy blocks with emesis, complete and partial responses were observed in 34 (80.9%) and 6 (14.3%) blocks, respectively, while 1/31(2.4%) patient had refractory vomiting. Mild sedation and transient transaminitis were the observed side effects.

Topics: Antiemetics; Antineoplastic Agents; Child; Humans; Nausea; Neoplasms; Olanzapine; Vomiting

The prevalence of nausea/vomiting in patients with advanced cancer has a wide range. Due to a very low level of evidence regarding antiemetic treatment, current guidelines recommend an etiology-based approach. The evidence for this approach is also slim and research is urgently needed.. (Part One) to elucidate the prevalence of nausea and the possible associations with sociodemographic and clinical variables and (Part Two) to investigate possible etiologies of nausea and antiemetic treatments initiated in patients with nausea.. Patients with advanced cancer and no recent antineoplastic treatment were included in a prospective two-part study. In Part One, patients completed an extended version of the EORTC QLQ-C15-PAL. Nauseated patients could then be included in Part Two in which possible etiologies and antiemetic treatment were recorded and a follow-up questionnaire was completed.. Eight hundred twenty-one patients were included and 46% reported any degree of nausea. Younger age and female sex were associated with a higher degree of nausea. Common etiologies included constipation, opioid use, and "other," and treatments associated with a statistically significant decrease in nausea/vomiting were olanzapine, laxatives, corticosteroids, domperidone, and metoclopramide.. Nausea was a common symptom in this patient population and many different etiologies were suggested. Most patients reported a lower degree of nausea at follow-up. More research in treatment approaches and specific antiemetics is strongly needed.

Topics: Adrenal Cortex Hormones; Adult; Age Factors; Aged; Aged, 80 and over; Antiemetics; Female; Humans; Male; Metoclopramide; Middle Aged; Nausea; Neoplasms; Olanzapine; Prevalence; Prospective Studies; Sex Factors; Surveys and Questionnaires; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse effect. Neurokinin-1 receptor antagonist (NK1RA)-containing regimens are the standard regimens for CINV prophylaxis in patients with cancer receiving highly or moderately emetogenic chemotherapy (HEC or MEC). NK1RA agents are expensive and were not registered in Sudan. Recently, regimens containing olanzapine, the available and affordable medication in Sudan, were introduced as another option. This study aimed to compare the efficacy of an olanzapine-containing regimen with the antiemetic regimen that was currently used in our institute for CINV prophylaxis in HEC/MEC settings.. The study prospectively compared an olanzapine-containing regimen (acute phase: olanzapine, ondansetron, dexamethasone; delayed phase: olanzapine, ondansetron) with an ondansetron/dexamethasone regimen (acute phase: ondansetron, dexamethasone; delayed phase: ondansetron) in adult patients with cancer receiving HEC or MEC. The study outcomes were complete response (CR; no emesis and no rescue medications) and nausea control (no nausea), which were assessed in the acute (0 to 24 hours), delayed (24 to 120 hours), and overall (0 to 120 hours) phases.. The study included 131 patients (olanzapine-containing: 50 patients; ondansetron/dexamethasone: 81 patients). CR and nausea control were higher in the olanzapine-containing than in the ondansetron/dexamethasone regimen (CR: acute phase, 86% v 71.6%; P = .086; delayed phase, 72% v 30.9%; P < .001; overall phase, 66% v 25.9%; P < .001; nausea control: acute phase, 86% v 74.1%; P = .127; delayed phase, 76% v 34.6%; P < .001; overall phase, 72% v 29.6%; P < .001). The major toxicity of olanzapine was grade 1 and 2 sedation or drowsiness (25 patients).. An olanzapine-containing regimen has better efficacy for prevention of CINV in the HEC/MEC setting. Oncologists working in a limited-resource setting should be familiar with olanzapine-containing regimens, because NK1RA agents are not affordable and not easily available.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Receptors, Neurokinin-1; Sudan; Vomiting; Young Adult

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine.

Topics: Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzodiazepines; Granisetron; Humans; Neoplasms; Olanzapine; Serotonin Antagonists; Vomiting

To compare the efficacy of antipsychotics (APs) for delirium treatment in patients with cancer, 27 patients treated with 1 of the 4 APs, haloperidol (HPD), risperidone (RIS), olanzapine (OLZ), and quetiapine (QTP), were divided into 2 groups: long half-life (T1/2; HPD, RIS, and OLZ) versus short T1/2 (QTP) or the multiacting receptor-targeted APs (MARTAs; OLZ and QTP) versus the non-MARTA (HPD and RIS). The symptom severity was evaluated by the memorial delirium rating scale (MDAS) on days 0, 3, and 7 following intervention. Significant improvements in total MDAS scores were found in all groups on day 3. However, on day 7, only the short T1/2 group and MARTA group showed significant improvement. Consideration of an AP's pharmacological properties may be helpful for improving the outcomes of pharmacological delirium intervention in patients with cancer.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cross-Sectional Studies; Delirium; Female; Half-Life; Haloperidol; Humans; Male; Middle Aged; Neoplasms; Olanzapine; Quetiapine Fumarate; Risperidone; Severity of Illness Index

Nausea and vomiting are among the most common and distressing symptoms in patients with advanced cancer. Olanzapine, an antipsychotic agent, is known to have an affinity for multiple neurotransmitter receptors. Previous studies have reported olanzapine to be efficacious in the treatment of nausea and vomiting. Although it has been administered at a number of facilities, its applicability to treat nausea and vomiting in patients with advanced cancer is poorly understood. We investigated the use of olanzapine for nausea and vomiting in patients with advanced cancer at multiple centers. This retrospective study was carried out at seven palliative care units and three facilities with palliative care teams in Japan from 2013 to 2015. The dosage of olanzapine, treatment duration, and duration from initial use until death were collected from the medical records. One hundred and eight patients met our inclusion criteria. The average dose of olanzapine was 3.6 mg (2.5 mg, n = 61; 5 mg, n = 46; 10 mg, n = 1) and average treatment duration was 18.7 days. The average duration from initial use until death was 39.0 days. There were no differences in the duration of administration until death between olanzapine doses (2.5 and 5 mg). Our results suggest that olanzapine have been used in patients with poor prognoses for nausea and vomiting in patients with advanced cancer. Conducting a prospective trial would further yield promising results.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Antipsychotic Agents; Benzodiazepines; Female; Humans; Japan; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Palliative Care; Patient Comfort; Retrospective Studies; Surveys and Questionnaires; Vomiting

While the efficacy of olanzapine in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) has been documented, the literature on the use of olanzapine as a rescue medication for breakthrough CINV has been scarce. The following study retrospectively evaluated the safety and efficacy of olanzapine for the treatment of breakthrough CINV. The efficacy and safety of olanzapine in the prophylactic setting was also examined in a smaller cohort.. Electronic medical records of adult patients aged >17 years receiving a prescription for olanzapine from the Odette Cancer Centre Pharmacy at Sunnybrook Hospital between January 2013 and June 2015 were reviewed retrospectively. Inclusion criteria required receiving one or more doses of olanzapine for the rescue or prophylaxis of CINV and documentation of the outcome.. A total of 154 patients and 193 treatment cycles were included in the breakthrough setting, while a total of 16 patients and 20 treatment cycles were included in the prophylaxis setting. In the breakthrough setting, 88% of cases experienced improved nausea, while 21% of cases reported improved vomiting. In the prophylactic setting, 100% of cases experienced improved nausea, while 65% achieved improved vomiting. A total of 43% of cases in the breakthrough setting and 65% of cases in the prophylactic setting experienced sedation.. Olanzapine is effective in improving CINV in both the prophylactic and breakthrough settings. The safety, efficacy, and appropriate dosage of olanzapine for the rescue of breakthrough CINV should be prospectively evaluated in a randomized controlled trial (RCT).

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Benzodiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Retrospective Studies; Treatment Outcome; Vomiting; Young Adult

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. The first generation 5-HT3 receptor antagonists have been very effective in the control of chemotherapy induced emesis in the first 24 h postchemotherapy (acute emesis), but have not been as effective against delayed emesis (24-120 h postchemotherapy). Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a FDA approved antipsychotic that blocks multiple neurotransmitters: dopamine at D1, D2, D3, D4 brain receptors, serotonin at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors, has emerged in recent trials as an effective preventative agent for chemotherapy-induced emesis and nausea, as well as a very effective agent for the treatment of breakthrough emesis and nausea. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Dexamethasone; Half-Life; Humans; Isoquinolines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quality of Life; Quinuclidines; Receptors, Neurokinin-1; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Antiemetics are being used both for the treatment and prophylaxis of opioid-induced nausea and vomiting (OINV) in clinical practice, despite the lack of evidence for the prophylactic benefit. Data regarding the actual status of prophylactic antiemetic use for OINV remain to be elucidated.. The objective of this study was to evaluate the practice among Japanese physicians of the prophylactic use of antiemetics when starting opioids prescription for the prevention of opioid-induced nausea and vomiting.. This questionnaire survey was targeted among physicians experienced in cancer pain treatment at two institutions of Japan (Nagoya University Hospital and Ichinomiya City Municipal Hospital). The questionnaire assessed the physicians' practice and beliefs regarding the prophylactic antiemetics prescription when they start opioids in patients with cancer pain.. Questionnaires were filled in and received from 112 physicians from two institutions. Eighty-two percent of physicians prescribed prophylactic antiemetics at the beginning of opioid prescription, and the most commonly prescribed drug for this purpose was prochlorperazine (88%).. Despite the lack of evidence, Japanese physicians commonly prescribe prophylactic antiemetics, most commonly prochlorperazine, for OINV. Prospective clinical trials are necessary to evaluate the efficacy of this practice.

Topics: Analgesics, Opioid; Antiemetics; Benzodiazepines; Chemoprevention; Domperidone; Health Care Surveys; Humans; Japan; Metoclopramide; Nausea; Neoplasms; Olanzapine; Pain; Practice Patterns, Physicians'; Prochlorperazine; Steroids; Vomiting

The role of olanzapine added to a dopamine antagonist and benzodiazepine for the treatment of refractory chemotherapy-induced nausea and vomiting (CINV) is incompletely characterized in all levels of chemotherapy emetogenicity. This retrospective study evaluated the efficacy of the addition of olanzapine in adults experiencing refractory CINV stratified by chemotherapy emetogenicity.. Thirty-three adults who experienced CINV refractory to guideline-recommended prophylaxis and breakthrough antiemetics (dopamine antagonists and benzodiazepines) and received at least one dose of olanzapine 5-10 mg per os were evaluated. Failure was defined as >5 emesis events in 24 h or more than 10 cumulative doses of rescue antiemetics following first olanzapine dose per treatment cycle. Post hoc analyses investigated variables impacting olanzapine efficacy.. The addition of olanzapine demonstrated an overall success rate of 70 %. This success rate did not differ between chemotherapy regimens of high versus low-to-moderate emetogenicity (p = 0.79), prophylaxis with serotonin antagonist plus corticosteroid and aprepitant versus serotonin antagonist alone (p = 0.77), or age over 50 versus ≤50 years (p > 0.99). A trend toward greater benefit was seen in women (p = 0.08).. The addition of olanzapine to a dopamine antagonist and benzodiazepine demonstrated high efficacy rates for refractory CINV irrespective of chemotherapy emetogenicity. The high success rates among all groups suggests that incomplete resolution of CINV with prophylactic serotonin antagonists and breakthrough dopamine antagonists plus benzodiazepine may benefit from the addition of olanzapine regardless of gender, degree of chemotherapy emetogenicity, number of prophylactic antiemetics, or age. The trend toward greater control of emesis in women merits further investigation.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Benzodiazepines; Dopamine Antagonists; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Retrospective Studies; Vomiting; Young Adult

Bowel obstruction is one of the most common complications in patients with advanced cancer. Incomplete bowel obstruction is one of the leading causes of nausea and vomiting, which may result in a substantial impairment to quality of life. We explored the antiemetic activity of olanzapine against nausea and vomiting in cancer patients with incomplete bowel obstruction. This retrospective study was carried out on a palliative care unit, using an electronic medical record from 2007 to 2009. The intensity of the symptom was evaluated and classified from the medical records on four scales. The frequency of vomiting also was noted from the medical records. During this study period, 20 patients met the inclusion criteria. The average dose of olanzapine was 4.9±1.2mg and treatment duration was 23.4±16.2 days. Olanzapine treatment led to a significant decrease in the average intensity score of nausea from 2.4±0.7 to 0.2±0.4 (P<0.001). Of the 20 patients, 18 (90%) experienced a reduction in the intensity of nausea. The average frequency of vomiting significantly decreased after olanzapine treatment from 1.1±1.3 times/day (median 0.5; range 0-4) before the treatment to 0.3±0.5 times/day (median 0; range 0-1) after the treatment (P<0.01). Before the treatment, 10 patients experienced vomiting; eight of these patients experienced a decrease in the frequency of vomiting with olanzapine treatment. Our study suggests the potential efficacy of olanzapine for relief of nausea in incomplete bowel obstruction. A prospective trial is promising.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Benzodiazepines; Female; Humans; Intestinal Obstruction; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Retrospective Studies; Treatment Outcome; Vomiting

Oral olanzapine is effective in controlling agitation in patients with delirium, but often, parenteral administration is necessary. Intramuscular (IM) olanzapine is approved for managing agitation in schizophrenia, but this route is inappropriate for terminally ill patients.. The purpose of this pilot study was to determine the safety and tolerability of subcutaneous (SC) olanzapine in the management of hyperactive or mixed delirium in patients with advanced cancer.. We conducted a prospective open-label study in patients with advanced cancer who had agitated delirium (Richmond Agitation Sedation Scale [RASS] score ≥+1) that had not responded to a 10mg or higher dose of parenteral haloperidol over 24 hours. Patients received olanzapine 5mg SC every eight hours for three days and continued haloperidol for breakthrough agitation. For patients requiring more than 8mg of rescue haloperidol daily, the olanzapine dose was increased to 10mg SC every eight hours. Injection site, systemic toxicity, and efficacy (RASS score <+1 and total haloperidol dose <8mg per 24 hours on the last study day) were evaluated.. Twenty-four patients received at least one olanzapine injection, and 15 (63%) completed the study. Median age of evaluable patients was 58 years (range 49-79), and 67% were males. No injection site toxicity was observed after 167 injections. Probable systemic toxic effects were observed in four patients (severe hypotension [blood pressure <90/50mmHg], paradoxical agitation, diabetes insipidus, and seizure). Efficacy was achieved in nine (37.5%) patients.. IM olanzapine is well tolerated subcutaneously. Further research is needed to evaluate its efficacy in controlling agitated delirium.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Delirium; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Olanzapine; Prospective Studies; Treatment Outcome

Mirtazapine and olanzapine are easy-to-use psychiatric drugs with potent antinausea effects. Ondansetron and later members of the 'setron class are currently standard treatments for cancer chemotherapy-related nausea and emesis. They are potent 5-HT3 blockers, but it is often not appreciated that mirtazapine and olanzapine bind with similar affinity to 5-HT3 receptors, have a longer half-life, are considerably cheaper than the 'setron class, and often offer better and smoother 24-h nausea control than 'setron class drugs. Mirtazapine and olanzapine often have salutary antianxiety effects and improve sleep quality. They occasionally relieve chemotherapy-related and advanced cancer-related nausea and appetite decrease better than the 'setron group that are specifically marketed for nausea control. Mirtazapine and olanzapine frequently give potent nausea reduction and appetite increase in advanced cancer-related cachexia. Several cytokine changes potentially induced by mirtazapine and olanzapine use are discussed that may have salutary effects in several cancers. We suggest mirtazapine and olanzapine be included as first-line options in treating both chemotherapy- and advanced cancer-related nausea. Multiple clinical and economic advantages of mirtazapine and olanzapine over currently used 'setron class medicines are reviewed. Double-blind studies against the 'setron class drugs are warranted.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Cachexia; Humans; Mianserin; Mirtazapine; Nausea; Neoplasms; Olanzapine; Ondansetron; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists

Recent investigations suggest the efficacy of olanzapine in cancer patients with intractable vomiting or chemotherapy-induced nausea. Olanzapine,indicated for schizophrenia in Japan, has an affinity for multiple neurotransmitter receptors including dopaminergic, serotonergic, histaminergic, adrenergic and muscarinic receptors. This pharmacological activity thus has a potential role in the treatment of nausea and vomiting. In the present study, olanzapine was given to five cancer patients with refractory vomiting to standard medications. In 3 cases, olanzapine resolved vomiting completely and also improved anorexia, In 2 cases, vomiting was controlled for a limited period. No adverse effect was observed. These results suggest olanzapine is a useful agent for the management of both vomiting and anorexia.

Topics: Aged; Anorexia; Antiemetics; Benzodiazepines; Female; Humans; Male; Middle Aged; Neoplasms; Olanzapine; Vomiting, Anticipatory

Chemotherapy-induced delayed emesis (DE) affects approximately 50-70% of patients receiving moderately and highly emetogenic chemotherapy. DE most commonly occurs within the first 24-48 hours of chemotherapy administration and can persist for 2-5 days. Olanzapine, which has been used anecdotally for chronic nausea in advanced cancer patients, might be a useful treatment for the prevention of delayed emesis in chemotherapy patients. We conducted a chart review to explore this hypothesis and to plan potential studies. Using pharmacy records or an electronic medical record, we identified all patients who had received olanzapine in the oncology clinic (n = 98). We reviewed these records and selected all patients (n = 28) who had received olanzapine for the prevention of delayed emesis for structured review. There were 17 women (60.7%) and 11 men (39.3%). Eleven patients (39.3%) had at least one instance of nausea recorded while undergoing olanzapine treatment and seven (25%) had an episode of vomiting recorded. During 95 total cycles of chemotherapy with olanzapine (mean = 3.4 cycles per patient), there were 21 incidents of nausea (22.1%) and 10 instances of vomiting (10.5%). Side effects were rarely noted. These data suggest that olanzapine was well tolerated and may reduce the incidence of delayed emesis in patients receiving moderate to highly emetogenic chemotherapy. A series of prospective trials are underway.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Neoplasms; Olanzapine; Pirenzepine; Retrospective Studies; Time Factors; Vomiting

This open-label pilot study explored the antiemetic activity of olanzapine, an atypical antipsychotic, in patients with advanced cancer requiring opioid analgesics for pain. Fifteen patients received 2 days of a washout and placebo "run-in" followed by two day periods on each of three doses of olanzapine (2.5 mgs, 5 mgs, and 10 mgs). Patients completed a daily food journal as well as the Mini Mental State Exam, Simpson Angus Scale, Barnes Akathisia Scale, and the Functional Assessment of Cancer Therapy-General across four time periods, with special attention being placed on the nausea item. Eleven women and 4 men with varied primary cancer sites participated. The average age of the sample was 58 years (SD = 16.8). All three dose levels were associated with significant reductions in nausea compared to baseline. Diary entries recorded by the subjects suggested substantial benefits to overall well being and the 5mg condition was associated with statistically significant improvement in overall quality of life over baseline (F = 12.0, p < 0.005). No extrapyramidal symptoms were noted and mental status exams were not changed over the course of the eight days. These results suggest an antiemetic effect for olanzapine and indicate the need for a controlled trial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Pain; Palliative Care; Pilot Projects; Pirenzepine

Topics: Adult; Antineoplastic Agents; Antipsychotic Agents; Benzodiazepines; Caffeine; Carcinogens; Chemoprevention; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Neoplasms; Olanzapine; Pirenzepine