Risk Factors Associated with Chemotherapy-Induced Nausea and Vomiting Among Women with Breast Cancer Receiving Highly Emetogenic Chemotherapy: Individual Patient-Based Analysis of Three Prospective Antiemetic Trials.

Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Methods: Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated. Results: Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and "no nausea" in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and "no nausea" in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. Conclusion: The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.

Efficacy and safety of low-dose amisulpride versus olanzapine-fluoxetine combination in post-schizophrenic depression: A randomized controlled trial.

Post-schizophrenic depression (PSD) increases the morbidity, mortality, and health burden in patients with schizophrenia. However, treatment of PSD is challenging due to the lack of substantial evidence of standard clinical practice. This study was aimed at comparing the efficacy and safety of low-dose amisulpride versus olanzapine-fluoxetine combination (OFC) in PSD. This was a randomized controlled trial conducted in sixty patients with PSD fulfilling the eligibility criteria. Recruited patients were randomized to receive either amisulpride at low dose (i.e., 100-300 mg/day) or OFC (5/10 mg + 20 mg) for eight weeks. The Calgary Depression Scale for Schizophrenia (CDSS), the Clinical Global Impression-Severity (CGI-S) and serum BDNF levels were assessed at baseline and after eight weeks of treatment. The change in the CDSS scores from baseline over eight weeks was significant in both the amisulpride and OFC groups. However, the changes were not significant when compared between the groups. Similarly, the changes in CGI-S scores and serum BDNF levels were significant in each group; but non-significant between the groups. A significant negative correlation was found between the changes in the CDSS scores and the serum BDNF levels in each group. No significant adverse events were noted in either group. Thus, to conclude, low-dose amisulpride can be a potential monotherapy in PSD with a favourable clinical outcome and safety profile (ClinicalTrials.gov ID: NCT04876521).

Pragmatic clinical trials to advance research in children and adolescents with eating disorders.

OBJECTIVE: To discuss the utility of pragmatic clinical trials (PCTs) to help advance research in eating disorders (EDs). METHODS: We describe challenges associated with traditional explanatory research trials and examine PCTs as an alternative, including a review of the PRECIS-2 tool. RESULTS: There are many challenges associated with the design and completion of traditional RCTs within the field of EDs. Pragmatic clinical trials are studies that closely align with conditions available in everyday practice and focus on outcomes that are relevant to patients and clinicians. Results of PCTS maximize applicability and generalizability to clinical settings. DISCUSSION: Available therapies established for the treatment of EDs provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In addition to a general overview of PCTs, we draw upon published literature and our own experiences involving adjunctive olanzapine for the treatment of children and youth with anorexia nervosa to help highlight challenges associated with randomized controlled trial (RCT) design and implementation, and offer pragmatic suggestions that would allow patients greater choice in treatment trials, while at the same time capturing outcomes that are most likely to advance treatment efforts. CONCLUSIONS: Pragmatic clinical trials provide alternatives to RCT design that can help bolster research in EDs that aims to explore real-world effects of interventions. PUBLIC SIGNIFICANCE: Available therapies established for the treatment of eating disorders (EDs) in children and adolescents provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In this article, we discuss the utility of pragmatic trials to help promote research that can help advance knowledge that is relevant to clinical care settings.

Effects of CYP2D6 gene polymorphism on plasma concentration and therapeutic effect of olanzapine.

This study aimed to evaluate the relationship between gene polymorphisms of metabolic enzymes, particularly the CYP2D6 gene, and the plasma concentration of olanzapine, as well as treatment response in patients with chronic schizophrenia. We recruited olanzapine-treated patients and examined their plasma olanzapine levels. Additionally, a common mutation site within each of the nine exons of the full-length CYP2D6 sequence was assayed. The Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and Overall Clinical Impression were used to assess schizophrenic symptoms, whereas the Barnes Akathisia Scale and Extrapyramidal Symptom Rating Scale were used to evaluate adverse effects. The results showed no significant differences in plasma olanzapine concentrations, treatment response, or the occurrence of adverse effects among different CYP2D6 genotypes. However, an association between olanzapine concentrations and improvement in clinical symptoms and adverse reactions was observed. In conclusion, the CYP2D6 genotype did not significantly impact plasma olanzapine concentrations, treatment response, or the occurrence of adverse effects.

Vitamin D3 and zinc supplements augment the antimanic efficacy of lithium and olanzapine treatments in an animal model of mania.

Objective: Bipolar disorder (BD) is a challenging psychiatric disorder and a complex disease. The associated reduction in serum vitamin D3 (VitD3) levels in BD patients and the contribution of zinc (Zn) to the treatment, along with the severe side effects of lithium (Li) treatment, were encouraging to assess the efficacy of different correlated combinations of therapeutic/nutraceutical treatments such as olanzapine (Oln), VitD3, and Zn against Li. Methods: Mania was induced in C57BL/6 mice by administering methylphenidate (MPH) for 14 consecutive days. On the 8th day of MPH injection, different treatment regimens were administered, Li, Oln, VitD3/Zn, VitD3/Zn/Oln, VitD3 + Zn + Oln + Li50mg/kg (C50), and VitD3 + Zn + Oln + Li100mg/kg (C100). Both VitD3 (850 IU/kg) and Zn (180 mg/kg) were supplied with food for 2 weeks before starting the induction of mania, which continued until the end of MPH administration. Behavioral, brain oxidative stress, thyroid hormones, VitD3, Zn, GsK-3ß, and Bcl2 levels, as well as brain histopathological alterations, were assessed. Results: Manic mice exhibited alterations in all tested parameters, and the histopathological examination of the cortex and hippocampus confirmed these results. The VitD3/Zn/Oln, C50, and C100 treatment regimens reversed most of the behavioral and pathophysiological alterations; however, the C50 treatment regimen was the most efficient. Conclusions: This study emphasizes the importance of combining different antimanic medications like Li and Oln with nutraceutical supplements to increase their antimanic efficacy, reduce their adverse effects, and, ideally, improve the BD patient's quality of life.

Continuous oral olanzapine or clozapine treatment initiated in adolescence has differential short- and long-term impacts on antipsychotic sensitivity than those initiated in adulthood.

One of the major discoveries in recent research on antipsychotic drugs is that antipsychotic treatment in adolescence could induce robust long-term alterations in antipsychotic sensitivity that persist into adulthood. These long-term impacts are likely influenced by various factors, including the "diseased" state of animals, sex, type of drugs, mode of drug administration, and age of treatment onset. In this study we compared the short- and long-term behavioral effects of 21-day continuous oral olanzapine (7.5 mg/kg/day) or clozapine (30.0 mg/kg/day) administration in heathy or maternal immune activated adolescent (33-53 days old) or adult (80-100 days old) rats of both sexes. We used a conditioned avoidance response model to assess the drug-induced alterations in antipsychotic sensitivity. Here, we report that while under the chronic drug treatment period, olanzapine progressively increased its suppression of avoidance responding over time, especially when treatment was initiated in adulthood. Clozapine's suppression depended on the age of drug exposure, with treatment initiated in adulthood showing a suppression while that initiated in adolescent did not. After a 17-day drug-free interval, in a drug challenge test, olanzapine treatment initiated in adolescence caused a decrease in drug sensitivity, as reflected by less avoidance suppression (a tolerance effect); whereas that initiated in adulthood appeared to cause an increase (more avoidance suppression, a sensitization effect). Clozapine treatments initiated in both adolescence and adulthood caused a similar tolerance effect. Our findings indicate that the same chronic antipsychotic treatment regimen initiated in adolescence or adulthood can have differential short- and long-term impacts on drug sensitivity.

Olanzapine for the prevention of postoperative nausea and vomiting after gynecologic laparoscopic surgery: a randomized controlled trial.

Purpose: This study was designed to investigate the prophylactic effect of oral olanzapine in postoperative nausea and vomiting after gynecologic laparoscopic surgery. Methods: ASA I-II, aged 18-75 years, planned to undergo gynecologic laparoscopic surgery with general anesthesia in adult female patients. Using the randomized numbers table, the patients were placed in two groups. Oral olanzapine 5 mg or placebo was given 1 h before anesthesia. All patients received standard antiemetic prophylaxis with dexamethasone and granisetron. The primary outcome was nausea and/or vomiting in the 24 h after the postoperative. Results: A total of 250 patients were randomized, and 241 were analyzed. The primary outcome occurred in 10 of 120 patients (8.3%) in the olanzapine group and 23 of 121 patients (19.2%) in the placebo group (p = 0.014). According to Kaplan-Meier analysis, the probabilities of nausea and/or vomiting in the 24 h after the postoperative in the olanzapine group were lower than in the placebo group (log-rank p = 0.014). In a multivariate Cox analysis, the variables of use of olanzapine [hazard ratio (HR): 0.35, 95% confidence interval (CI): 0.16-0.79; p = 0.012] and use of vasoactive drugs (HR: 2.48, 95% CI: 1.07-5.75; p = 0.034) were independently associated with nausea and/or vomiting in the 24 h after the postoperative. Conclusion: Our data suggest that olanzapine relative to placebo decreased the risk of nausea and/or vomiting in the 24 h after gynecologic laparoscopic surgery. Trial registration: The trial was registered prior to patient enrollment at The Chinese Clinical Trial Registry (https://www.chictr.org.cn/showproj.html?proj=166900, link to registry page, Principal investigator: Nanjin Chen, Date of registration: 25 April 2022).

Preventing nausea and vomiting after laparoscopic gynecological surgery: the benefits of using olanzapine Why was this study done? Despite the use of antiemetics, postoperative nausea and vomiting remain prevalent. Furthermore, patients who undergo gynecological laparoscopic surgery are at an increased risk. Therefore, this study investigated whether oral Olanzapine could reduce the incidence of nausea and vomiting after gynaecological Laparoscopy? What did the researchers do? The research team examined patients who underwent gynecological laparoscopic surgery under general anesthesia. They observed the occurrence of nausea and vomiting within 24 hours after surgery in patients who either received or did not receive Olanzapine treatment. The goal was to assess the effectiveness of Olanzapine in reducing postoperative nausea and vomiting. What did the researchers find? The addition of Olanzapine, when combined with granisetron and dexamethasone, resulted in a decreased risk of nausea and/or vomiting within the 24 hours following gynecologic laparoscopic surgery, as compared to the placebo. Administering oral Olanzapine at a dosage of 5 mg reduced the incidence of nausea and vomiting after gynecological laparoscopy from 19.2% to 8.3%. What do the findings mean? This study has identified a safe and effective medication for preventing postoperative nausea and vomiting. Implementing Olanzapine as a preventive measure can significantly reduce the incidence of nausea and vomiting following surgery, thereby enhancing the overall medical experience for patients.

Olanzapine-Samidorphan for Schizophrenia: A Systematic Review and Meta-Analysis.

Background and Objective: United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse events (weight gain) in adult patients with schizophrenia and bipolar disorder. To opine about the safety and efficacy of OLZSAM, authors performed a systematic review and meta-analysis to convene justifiable evidence. Methods: A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, from inception to September 2022, with the keywords: 'olanzapine and samidorphan' and schizophrenia; and "ALKS3831" and "lybalvi." Clinical trials published in English that analyzed the efficacy and safety of OLZSAM were included. The significant outcomes included in this study were change from baseline (CFB) in Positive and Negative Syndrome Scale (PANSS) at the end of the study, the proportion of patients with weight gain at the end of the study, the proportion of patients with at least one adverse event, and the incidence of drug discontinuation due to adverse events. Results: The change in PANSS score at the end of the study was comparable among groups receiving OLZSAM and olanzapine alone: standardized mean difference (SMD) = 0.04; 95% CI = -0.09 to 0.17; p = 0.57. The OLZSAM group reported less incidence of weight gain: risk ratio (RR) = 0.91; 95% CI = 0.62-1.34; p = 0.63, and any adverse event: RR = 0.99; 95% CI = 0.90-1.09; p = 0.81. Drug discontinuation incidence was higher in the OLZSAM group: RR = 1.22; 95% CI = 0.84-1.79; p = 0.30. Conclusions: The combination OLZSAM showed comparable efficacy to olanzapine alone in schizophrenia patients, with relatively less incidence of weight gain and adverse events; however, the drug discontinuation due to adverse events was more in the OLZSAM group.

Modulation of hemispheric asymmetry in executive control of attention in schizophrenia with atypical antipsychotic treatment: Potential benefits of olanzapine.

Deficits in executive control of attention have been reported in schizophrenia patients, but can be ameliorated by treatment of atypical antipsychotics along with the symptoms. However, it remains unclear whether this effect is related to a modulation of hemispheric asymmetry in executive control by the medicine. In this behavioral study, we employed a lateralized version of the attention network test to examine the hemispheric asymmetry of executive control in schizophrenia patients before and after olanzapine treatment, compared to matched healthy controls. Executive control was measured as a conflict effect, indexed as the response time (RT) difference between incongruent versus congruent flanker conditions, and was compared between stimuli presented in the left and the right visual field (i.e., processed by right versus left hemisphere of the brain). Results showed that pre-treatment schizophrenia patients revealed a right hemisphere superiority in conflict effect (i.e., a smaller effect in the right hemisphere than in the left hemisphere), driven by the incongruent condition. Olanzapine treatment reduced this right hemisphere superiority by improving the efficiency of the left hemisphere in the incongruent condition. These results suggested that olanzapine treatment may improve the efficiency of executive control in the left hemisphere in schizophrenia patients.

Effects of Aripiprazole on Olanzapine Population Pharmacokinetics and Initial Dosage Optimization in Schizophrenia Patients.

Objective: Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains unclear. The purpose of this study was to explore the drug-drug interaction (DDI) of multiple drugs combined with olanzapine and to recommend the optimal administration of olanzapine in schizophrenia patients. Methods: In this study, we obtained olanzapine concentrations from therapeutic drug monitoring (TDM) database. In addition, related medical information, such as physiological, biochemical indexes, and concomitant drugs was acquired using medical log. Sixty-five schizophrenia patients were enrollmented for analysis using population pharmacokinetic model by means of nonlinear mixed effect (NONMEM). Results: Weight and combined use of aripiprazole significantly affected olanzapine clearance. Without aripiprazole, for once-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-70, and 70-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.6, 0.5 mg/kg/day were recommended for 40-60, and 60-100 kg schizophrenia patients, respectively. With aripiprazole, for once-daily olanzapine administration dosages, 0.4, 0.3 mg/kg/day were recommended for 40-53, and 53-100 kg schizophrenia patients, respectively; for twice-daily olanzapine administration dosages, 0.4 mg/kg/day was recommended for 40-100 kg schizophrenia patients, respectively. Conclusion: Aripiprazole significantly affected olanzapine clearance, and when schizophrenia patients use aripiprazole, the olanzapine dosages need adjust. Meanwhile, we firstly recommended the optimal initial dosages of olanzapine in schizophrenia patients.

Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model.

BACKGROUND: Olanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. METHODS: Rats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5-40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. RESULTS: In adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. CONCLUSIONS: These results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.

A Review of Advances in Bioanalytical Methods for the Detection and Quantification of Olanzapine and Its Metabolites in Complex Biological Matrices.

Schizophrenia is a serious mental disorder that significantly affects the social and professional life of patients, causing distortion of reality and loss of identity and cognitive abilities. Psychopharmacological treatment is an integral part of modern psychiatry, and the introduction of new "atypical" antipsychotic drugs has brought significant progress in the treatment of this disorder. One of these drugs is olanzapine, which has an effective effect on the productive symptoms of schizophrenia while having an almost minimal potential to cause extrapyramidal syndrome. However, its effectiveness is confronted with frequent side effects, referred to as "metabolic disorders". Therefore, to ensure the effectiveness of treatment and to minimize the side effects caused by olanzapine, it is recommended to monitor the drug level during therapy. This article reviews the bioanalytical methodologies that enable efficient extraction and sensitive analysis of olanzapine. We considered the advantages and disadvantages of different sample pretreatment methods, including traditional and novel strategies. The analytical conditions required for the separation and detection of olanzapine and its metabolites were analyzed using chromatographic methods combined with various detectors.

Olanzapine-induced weight gain and lipid dysfunction in mice between different gender.

As one of the most common antipsychotics, olanzapine may cause metabolic-related adverse effects, but it is still unknown how olanzapine alters lipid metabolism. In this study, we found that olanzapine-treated mice showed varying degrees of dyslipidemia, which was particularly pronounced in female mice. Based on ultra-performance liquid chromatography-quadrupole time-of-flight-MS (UPLC-Q-TOF-MS) technology and lipid metabolomics, we mapped the changes in lipid metabolism in olanzapine-treated mice and then compared the changes in lipid metabolism between male and female mice. There were 98 metabolic differentiators between the olanzapine-treated and control groups in females and 79 in males. These metabolites were glycerolipids, glycerophospholipids, fatty amides, and sphingolipids, which are involved in glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. These results suggest that olanzapine-induced changes in the levels of lipid metabolites are closely associated with disturbances in lipid metabolic pathways, which may underlie lipemia. This lipidome profiling study not only visualizes changes in lipid metabolism in liver tissue but also provides a foundation for understanding the regulatory pathways and mechanisms involved in olanzapine-induced lipid metabolism disorders. Furthermore, this study demonstrates differences in lipid metabolism between males and females, providing a reference for clinical treatment regimen selection.

Olanzapine Liquisolid Tablets Using Kolliphor EL with Improved Flowability and Bioavailability: In vitro and In vivo Characterization.

Objectives: Liquisolid tablets are an innovative approach to enhance the dissolution rate and, thereby, the bioavailability of therapeutic agents with poor aqueous solubility. Materials and Methods: The objective of the current research was to compare the bioavailability of the optimized formulation of the olanzapine (OLZ) liquisolid tablet with that of the marketed tablet (MT) by conducting pharmacokinetic and behavioral assessment studies. Ten formulations were designed using Kolliphor EL as a non-volatile solvent, and the respective tablets were prepared by the direct compression method. Results: Pre-compression studies of powders of all the formulations showed good/excellent flow properties and compressibility. The drug release profiles of liquisolid tablets were determined and compared with those of MT. Based on the in vitro results, K250 was considered as an optimized formulation and selected for further in vivo studies. AUC0-∞ value of K250 formulation was found to be 357.2 ± 35.5 ng.h.mL-1, which was higher than that of the MT (258.4 ± 29.9 ng.h.mL-1). The reduction in locomotor activity was enhanced remarkably in K250 compared with MTs at p < 0.05. The time periods taken to fall in the rotarod test were approximately equal in the experimental groups, which indicated the absence of extrapyramidal side effects. There was a remarkable decrease in the number of boxes covered in the open field test. Conclusion: Kolliphor EL was found to be a potential non-volatile solvent that can be used to produce liquisolid tablets of OLZ with improved flow, compressibility, dissolution, and bioavailability.

A Possible Role of Akkermansia muciniphila in the Treatment of Olanzapine-Induced Weight Gain.

Second-generation antipsychotics are mainly used in both acute and long-term treatment of major psychiatric disorders. Although better tolerated than first-generation antipsychotic drugs, they can frequently induce weight gain and metabolic disorders, of these, olanzapine is one of the drugs more likely to induce these side effects. There is consistent evidence of the role of gut microbiota in modulating the gut-brain axis with complex crosstalk with the host involving satiety signaling pathways, food intake behavior, and weight and metabolic regulation. Second-generation antipsychotics induce important gut microbiota modification thus contributing together with the central and peripheral receptors blockade mechanism to weight gain induction and metabolic impairment. These drugs can alter the composition of gut microbiota and induce dysbiosis, often reducing the concentration of Akkermansia muciniphila, a bacterium that is also decreased in patients with diabetes, obesity, metabolic syndrome, or chronic inflammatory diseases. Probiotic administration can be a safe and well-tolerated approach to modulate microbiota and offer an integrative strategy in psychiatric patients suffering antipsychotic side effects. Multiple strain probiotics and Akkermansia muciniphila alone have been administered both in mice models and in clinical populations demonstrating efficacy on antipsychotic-induced metabolic impairment and showing a contribution in reducing induced weight gain. Akkermansia muciniphila can improve several parameters altered by olanzapine administration, such as weight gain, insulin resistance, hyperglycemia, liver function, systemic inflammation, and gut barrier function. Although we do not have jet trials in the psychiatric population, this probiotic may be a complementary approach to treating olanzapine-induced weight gain and metabolic side effects.

Precipitated opioid withdrawal in a patient started on olanzapine/samidorphan.

BACKGROUND: Olanzapine/Samidorphan (Lybalvi®) is a novel oral agent for the treatment of schizophrenia and bipolar I disorder. It was designed to reduce weight gain associated with olanzapine. Samidorphan is an analog of naltrexone, initially intended to treat substance use disorders by antagonizing mu, delta, and kappa opioid receptors. CASE REPORT: We present the case of a 36-year-old who took their first dose of olanzapine/samidorphan shortly before calling for emergency services. The patient took diphenhydramine and an epinephrine autoinjector for what they thought was an allergic reaction but continued to have symptoms. EMS reported involuntary muscle movements thought to be due to dystonia from olanzapine. In the ED, they experienced generalized muscle spasms lasting for several seconds and diaphoresis. Initially, the staff treated for a presumed dystonic reaction to olanzapine and administered diphenhydramine 25 mg IV, diazepam 2 mg IV, midazolam 5 mg IV, and benztropine 1 mg IV without improvement. It was later determined that the patient took 16 mg of buprenorphine SL daily. With this information, precipitated opioid withdrawal was felt to be the likely cause of symptoms. The patient received 16 mg of buprenorphine for an initial Clinical Opiate Withdrawal Scale (COWS) score of 11 with repeat COWS of 6. Why should an emergency physician be aware of this? Initiating olanzapine/samidorphan in the setting of chronic opioid therapy may result in precipitated opioid withdrawal. Additional SL buprenorphine may be a reasonable treatment modality.

Association between olanzapine plasma concentrations and treatment response: A systematic review, meta-analysis and individual participant data meta-analysis.

AIMS: By meta-analysing pooled studies and available individual participant data, we aim to provide new insight on olanzapine therapeutic drug monitoring in schizophrenia. METHOD: We conducted a computerized search of bibliographic databases (Pubmed, Cochrane library, Web of Science and PsycINFO) to identify studies that assessed the relationship between olanzapine plasma concentration and the change in patients' clinical scores. We investigated this relationship with olanzapine plasma level 12h00 post-intake using a random-effects model. RESULTS: 7 studies were included in the pooled data analysis (781 patients). We found no difference in oral dose between responders and non-responders but a significantly higher concentration of 4.50 µg/L in responders (p < 0.01). Olanzapine concentration above the thresholds identified in each study was associated with response (odd ratio = 3.50, p = 0.0007). We identified that non-responder patients showed greater inter-individual variability than responders. In the individual data analysis (159 patients), we found no relationship between dose and clinical response but an association between plasma level and response in the shape of a parabolic curve. The Receiver Operating Characteristic curve found a threshold of 22.07 µg/L to identify responders (96% sensitivity, 86% specificity) and a threshold of 56.47 µg/L to identify a decreased probability of response. CONCLUSION: In contrast to oral dose, our work confirmed that plasma olanzapine levels are associated with clinical response and should therefore be used to optimise treatment. We determined a treatment response threshold of 22.07 µg/L and suggest that a concentration above the therapeutic window may result in a decreased response.

Refeeding syndrome and psychopharmacological interventions in children and adolescents with Anorexia Nervosa: a focus on olanzapine-related modifications of electrolyte balance.

This study aims to investigate the potential correlation between the use of olanzapine, a psychopharmacological intervention commonly prescribed in Anorexia Nervosa treatment, and the occurrence of Refeeding Syndrome. Despite the acknowledged nutritional and biochemical impacts of olanzapine, the literature lacks information regarding its specific association with Refeeding Syndrome onset in individuals with Anorexia Nervosa. This is a naturalistic, retrospective, observational study, reporting the occurrence of Refeeding Syndrome in children and adolescents with Anorexia Nervosa, treated or untreated with olanzapine. Dosages and serum levels of olanzapine were assessed for potential associations with the occurrence of Refeeding Syndrome and specific variations in Refeeding Syndrome-related electrolytes. Overall, 113 patients were enrolled, including 46 (41%) who developed a Refeeding Syndrome. Mild (87%), moderate (6.5%), and severe (6.5%) Refeeding Syndrome was described, at a current average intake of 1378 ± 289 kcal/day (39 ± 7.7 kcal/kg/die), frequently associated with nasogastric tube (39%) or parenteral (2.2%) nutrition. Individuals receiving olanzapine experienced a more positive phosphorus balance than those who did not (F(1,110) = 4.835, p = 0.030), but no difference in the occurrence of Refeeding Syndrome was documented. The mean prescribed doses and serum concentrations of olanzapine were comparable between Refeeding Syndrome and no-Refeeding Syndrome patients.    Conclusion: The present paper describes the occurrence of Refeeding Syndrome and its association with olanzapine prescriptions in children and adolescents with Anorexia Nervosa. Olanzapine was associated with a more positive phosphorus balance, but not with a different occurrence of Refeeding Syndrome. Further, longitudinal studies are required. What is Known: • Refeeding Syndrome (RS) is a critical complication during refeeding in malnourished patients, marked by electrolyte (phosphorus, magnesium, potassium) imbalances. • Olanzapine, an atypical antipsychotic with nutritional and biochemical impacts, is used in Anorexia Nervosa (AN) treatment, however data concerning its association with RS are lacking. What is New: • The study observed RS in 46/113 (41%) young patients with AN. • Olanzapine-treated individuals showed a higher improvement in serum phosphate levels than untreated ones, although no impact on the occurrence of Refeeding Syndrome was observed.