-
Psychological Medicine Sep 2022Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants.... (Meta-Analysis)
Meta-Analysis Review
Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04-1.73 and 1.07-1.67, respectively] to 2.17 for risperidone (95% CrI 1.38-3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96-1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50-0.91), brexpiprazole (OR 0.69, 95% CrI 0.55-0.86), and cariprazine (OR 0.61, 95% CrI 0.46-0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25-1.07) and risperidone (OR 0.48, 95% CrI 0.10-2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.
Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Humans; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate; Risperidone
PubMed: 35993319
DOI: 10.1017/S0033291722001246 -
The American Journal of Psychiatry Jun 2019This study evaluated the benefits of olanzapine compared with placebo for adult outpatients with anorexia nervosa. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study evaluated the benefits of olanzapine compared with placebo for adult outpatients with anorexia nervosa.
METHODS
This randomized double-blind placebo-controlled trial of adult outpatients with anorexia nervosa (N=152, 96% of whom were women; the sample's mean body mass index [BMI] was 16.7) was conducted at five sites in North America. Participants were randomly assigned in a 1:1 ratio to receive olanzapine or placebo and were seen weekly for 16 weeks. The primary outcome measures were rate of change in body weight and rate of change in obsessionality, assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS).
RESULTS
Seventy-five participants were assigned to receive olanzapine and 77 to receive placebo. A statistically significant treatment-by-time interaction was observed, indicating that the increase in BMI over time was greater in the olanzapine group (0.259 [SD=0.051] compared with 0.095 [SD=0.053] per month). There was no significant difference between treatment groups in change in the YBOCS obsessions subscale score over time (-0.325 compared with -0.017 points per month) and there were no significant differences between groups in the frequency of abnormalities on blood tests assessing potential metabolic disturbances.
CONCLUSIONS
This study documented a modest therapeutic effect of olanzapine compared with placebo on weight in adult outpatients with anorexia nervosa, but no significant benefit for psychological symptoms. Nevertheless, the finding on weight is notable, as achieving change in weight is notoriously challenging in this disorder.
Topics: Adolescent; Adult; Ambulatory Care; Anorexia Nervosa; Body Mass Index; Double-Blind Method; Female; Humans; Male; Middle Aged; Obsessive Behavior; Olanzapine; Selective Serotonin Reuptake Inhibitors; Time Factors; Weight Gain; Young Adult
PubMed: 30654643
DOI: 10.1176/appi.ajp.2018.18101125 -
JAMA Oncology Jun 2020Nausea and vomiting, unrelated to chemotherapy, can be substantial symptoms in patients with advanced cancer. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Nausea and vomiting, unrelated to chemotherapy, can be substantial symptoms in patients with advanced cancer.
OBJECTIVE
To evaluate the utility of olanzapine for treating chronic nausea/vomiting, unrelated to chemotherapy, in patients with advanced cancer.
DESIGN, SETTING, AND PARTICIPANTS
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).
INTERVENTIONS
Patients received olanzapine (5 mg) or a placebo, orally, daily for 7 days.
MAIN OUTCOMES AND MEASURES
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.
RESULTS
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.
CONCLUSIONS AND RELEVANCE
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.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03137121.
Topics: Adult; Aged; Antiemetics; Double-Blind Method; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Pilot Projects; Vomiting
PubMed: 32379269
DOI: 10.1001/jamaoncol.2020.1052 -
BMJ Case Reports Mar 2023Olanzapine is a commonly used and effective second-generation antipsychotic agent used for the control of paranoia and agitation in schizophrenia and bipolar disorder as...
Olanzapine is a commonly used and effective second-generation antipsychotic agent used for the control of paranoia and agitation in schizophrenia and bipolar disorder as well as in the behavioural and psychological symptoms of dementia. Serious side effects of treatment are uncommon but spontaneous rhabdomyolysis represents a rare complication. We describe here a patient treated with a stable dose of olanzapine for more than 8 years who developed acute severe rhabdomyolysis without an identifiable trigger and without features suggestive of neuroleptic malignant syndrome. The rhabdomyolysis was atypical in its delayed onset and severity with a creatine kinase level of 345 125 U/L, the highest level reported in the available literature. We also describe the clinical manifestations of delayed-onset olanzapine-induced rhabdomyolysis and its differentiation from neuroleptic malignancy syndrome, and we highlight key aspects of management to prevent or minimise further complications such as acute kidney injury.
Topics: Humans; Olanzapine; Benzodiazepines; Antipsychotic Agents; Schizophrenia; Neuroleptic Malignant Syndrome; Rhabdomyolysis
PubMed: 36898712
DOI: 10.1136/bcr-2022-254377 -
Klinicka Onkologie : Casopis Ceske a... 2022Olanzapine is an effective antipsychotic drug used in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders. It belongs to the 2nd... (Review)
Review
BACKGROUND
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.
PURPOSE
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.
CONCLUSION
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
PubMed: 35989084
DOI: 10.48095/ccko2022276 -
Drugs Aug 2021Samidorphan, which was developed by Alkermes, is an opioid receptor antagonist that has been co-formulated with olanzapine into a single-dose oral tablet to mitigate the... (Review)
Review
Samidorphan, which was developed by Alkermes, is an opioid receptor antagonist that has been co-formulated with olanzapine into a single-dose oral tablet to mitigate the risk of weight gain while providing the therapeutic effect of olanzapine. Olanzapine/samidorphan (LYBALVI) was recently approved in the USA for the treatment of schizophrenia and bipolar I disorder. This article summarizes the milestones in the development of samidorphan leading to this first approval of olanzapine/samidorphan.
Topics: Antipsychotic Agents; Bipolar Disorder; Drug Combinations; Humans; Naltrexone; Narcotic Antagonists; Olanzapine; Schizophrenia; Weight Gain
PubMed: 34304374
DOI: 10.1007/s40265-021-01568-0 -
Acta Psychiatrica Scandinavica Sep 2020In this paper, we aimed at reviewing evidence-based treatment options for bipolar mania and proposed tentative evidence-based clinical suggestions regarding the... (Review)
Review
OBJECTIVE
In this paper, we aimed at reviewing evidence-based treatment options for bipolar mania and proposed tentative evidence-based clinical suggestions regarding the management of a manic episode, especially regarding the choice of the proper mood stabilizer and antipsychotic medication.
METHOD
A narrative review was undertaken addressing 'treatment of bipolar mania'. Findings have been synthesized and incorporated with clinical experience into a model to support different treatment choices.
RESULTS
To date, there is solid evidence supporting the use of several medications, such as lithium, divalproex, and carbamazepine, and antipsychotics, such as chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, inhaled loxapine, asenapine, and cariprazine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment-refractory cases. However, in clinical practice, when making decisions about treatment, personalized treatment is needed, according to the different clinical presentations and more complex clinical situations within the manic episode and considering a long-term view and with the objective of not only a symptomatic but also functional recovery. After remission from acute mania, psychoeducation strategies are useful to ensure adherence.
DISCUSSION
Despite the evidence forefficacy of many currently available treatments for mania, the majority of RCTs provide little direction for the clinician as to what steps might be optimal in different presentations of mania as well as in the presence of specific patient characteristics. Manic episodes should be managed on a personalized basis considering the clinical course and patient criteria and with the expectation of maintaining that treatment in the long-term.
Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Mania; Olanzapine
PubMed: 33460070
DOI: 10.1111/acps.13209 -
BMJ Open Jan 2023Clozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including...
Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry).
INTRODUCTION
Clozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacological/behavioural interventions have had limited effects counteracting these adverse effects. Semaglutide, a glucagon-like peptide 1 receptor agonist, is approved for the treatment of type 2 diabetes and obesity. We will investigate the long-term effects of add-on treatment with semaglutide once a week versus placebo once a week on the metabolic status in pre-diabetic (glycated haemoglobin A1c (HbA1c) 35-47 mmol/mol (5.4%-6.4%) and diabetic (HbA1c 48-57 mmol/mol (6.5%-7.4%)) patients diagnosed with a schizophrenia spectrum disorder who initiated clozapine or olanzapine treatment within the last 60 months.
METHODS AND ANALYSIS
This is a 26-week, double-blinded, randomised, placebo-controlled trial. Altogether, 104 patients diagnosed with a schizophrenia spectrum disorder, aged 18-65 years, with pre-diabetes or diabetes will be randomised to injections of 1.0 mg semaglutide once a week or placebo for 26 weeks. The primary endpoint is change from baseline in HbA1c. Secondary endpoints include changes in body weight, hip and waist circumference and plasma levels of insulin, glucagon, glucose, and C-peptide, insulin sensitivity, beta cell function, hepatic function, fibrosis-4 score, lipid profile, incretin hormones, bone markers, body composition, bone density, proteomic analyses and oxidative stress markers. Together with alcohol, tobacco and drug use, potential effects on the reward value of a sweet-fat stimulus, psychopathology, level of activity and quality of life will also be assessed.
ETHICS AND DISSEMINATION
This study is approved by the Danish Medicines Agency and the regional scientific ethics committee of the Capital Region of Denmark (committee C, #H-20019008) and will be carried out in accordance with International Council for Harmonisation Good Clinical Practice guidelines and the Helsinki Declaration. The results will be disseminated through peer-review publications and conference presentations.
TRIAL REGISTRATION NUMBER
NCT04892199.
Topics: Humans; Schizophrenia; Clozapine; Olanzapine; Glucagon-Like Peptide-1 Receptor; Prediabetic State; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Proteomics; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36720576
DOI: 10.1136/bmjopen-2022-068652 -
The Primary Care Companion For CNS... Aug 2023
Topics: Humans; Bradycardia; Olanzapine
PubMed: 37595163
DOI: 10.4088/PCC.22cr03453 -
Annals of Emergency Medicine Apr 2019
Topics: Emergency Service, Hospital; Haloperidol; Midazolam; Olanzapine; Piperazines; Thiazoles
PubMed: 30902175
DOI: 10.1016/j.annemergmed.2018.11.020