Schizophrenia is associated with high treatment nonadherence and economic burden in the United States. Long-acting injectable (LAI) antipsychotics may improve adherence and reduce relapse risk, but comparative cost-effectiveness data of second-generation antipsychotic (SGA) LAIs in the United States remain limited. To compare the cost-effectiveness of treatment strategies initiating with 4 SGA LAIs, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, and risperidone, with the strategy initiating with monthly paliperidone palmitate in patients with schizophrenia from the US health care sector perspective. A Markov model with 90-day cycles was developed to simulate the progression of 40-year-old adults transitioning among stable treated, stable nontreated, and relapse health states and death over 5years at a 3% discount rate. Patients transitioned to additional lines of therapy (another SGA LAI and then clozapine) after relapse or intolerance to side effects. Transition probabilities were derived from US claims-based observational studies, clinical trials, and meta-analyses. Health state utilities and disutilities due to extrapyramidal symptoms, weight gain, and diabetes from published literature were applied to age-adjusted utility of the US population. Compared with the treatment strategy initiating with paliperidone (3.22 quality-adjusted life-years [QALYs]), treatment strategies initiating with the other SGA LAIs generated slightly lower to similar QALYs. Strategies initiating with aripiprazole monohydrate and risperidone were dominated by the paliperidone-initiating strategy. Strategies initiating with aripiprazole lauroxil and olanzapine resulted in lower total health care costs but lower QALYs, with incremental cost-effectiveness ratios of $242,477 and $2,887, respectively. Sensitivity analysis confirmed the robustness of these findings, with LAI drug costs and relapse probabilities being the most influential parameters. Over a 5-year horizon, the treatment strategy initiating with paliperidone emerged as a favorable LAI option, providing the highest QALY gains at comparable or lower costs than the other LAI-initiating strategies.

Efficacy of Low-Dose Olanzapine for the Prevention of Conditioning Therapy-Induced Nausea and Vomiting in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Background: The key parameters determining the bioavailability of an active pharmaceutical ingredient are its solubility/dissolution rate in physiological fluids and permeability across biological membranes. Highly accurate in vitro prediction of bioavailability is a key issue that typically arises during the development of new drug formulations and the improvement of existing ones. Objectives: The objective of the present work is to study the dissolution/release and permeation of olanzapine (OLZ) from two- and three-component solid dispersions (SDs) with sulfobutylether-β-cyclodextrin (SBE-β-CD) and several pharmaceutical adjuvants as solubilizing agents. Methods: Solid dispersions were prepared by mechanical grinding and characterized with X-ray Phase analysis (PXRD), Fourier Transform Infrared (FTIR) and Raman spectroscopy, Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). Results: Raman spectroscopy was shown to be the best for revealing the interactions of OLZ with SBE-β-CD and γ-aminobutyric acid (GABA) in the three-component SD. The kinetic dependences of OLZ release and diffusion through the cellulose membrane were thoroughly described by quantitative parameters and classified according to the drug release mechanism. Significant improvement of release rate, OLZ concentration, and permeation with SDs compared to the pure OLZ was demonstrated. Conclusions: It was shown that the selected dispersions were stable when stored under normal conditions but underwent changes upon exposure to elevated temperature and humidity. The nature of these changes was determined by the properties of the components and their mutual interactions.

Substance use is a major contributor to psychiatric emergencies, often complicating the management of acute agitation. Despite the high prevalence of co-occurring substance use in emergency psychiatric settings, evidence guiding pharmacologic interventions remains limited. This study examined whether active substance use, as measured by urine drug screening (UDS), predicted clinical and safety outcomes among patients requiring intramuscular (IM) medication for agitation in an emergency psychiatric setting. This retrospective chart review included 103 patients presenting to a Comprehensive Psychiatric Emergency Program (CPEP) between January 2020 and November 2022 who received IM haloperidol lactate (HL) or IM olanzapine (OL) and completed UDS. Patients with positive (UDS+) screens were compared to those with negative (UDS-) screens on demographic, clinical, and medication-related outcomes. Primary medication outcomes were the need for repeat IM medication administration and time to next administration. Secondary measures included physiologic changes, adverse effects, and restraint/seclusion use. Fifty-eight patients (56.3%) had a positive UDS. The UDS+ group was younger and more frequently had an incarceration history, but did not differ from the UDS- group in terms of diagnoses, hospitalization history, or adverse events. UDS+ patients had a significantly longer time to next medication administration (mean 10.0 vs 6.5 hours, P = .050). There were no differences in terms of repeat IM use, objective measures of agitation, or safety outcomes. Subanalysis comparing HL and OL among UDS+ patients was limited by sample size, but showed comparable efficacy and tolerability. Patients with active substance use exhibited similar or greater responses to standard IM treatment for agitation without increased safety concerns. Findings support potential safety and efficacy of common pharmacologic approaches in this high-risk population, though a modest single-site cohort may limit generalizability. There is a need for prospective, multisite replication.

Intramuscular (IM) olanzapine has become an important therapeutic option in the management of acute agitation and long-term treatment of psychiatric disorders such as schizophrenia and bipolar disorder. Although oral olanzapine is commonly prescribed, IM formulations—including short-acting injections for acute behavioural disturbances and long-acting injectable (LAI) olanzapine pamoate for maintenance therapy—play a crucial role when rapid symptom control or improved treatment adherence is required. IM olanzapine provides rapid onset of action by bypassing first-pass metabolism and achieving peak plasma levels within a short period, making it effective in emergency psychiatric situations. The LAI formulation helps maintain stable therapeutic drug levels, thereby reducing relapse, rehospitalization, and medication non-adherence in patients with chronic schizophrenia. However, the safe administration of IM olanzapine requires careful clinical assessment and specialized nursing techniques. Comprehensive nursing responsibilities include pre-administration evaluation of mental status, vital signs, comorbidities, and medication history; correct injection technique using recommended sites and aseptic procedures; and continuous post-injection monitoring. Particular attention is required for the rare but serious complication known as Post-Injection Delirium/Sedation Syndrome (PDSS), which necessitates mandatory observation after administration. In addition, nurses play a key role in documentation, patient education, and early recognition of adverse reactions such as hypotension, sedation, and respiratory depression. Overall, effective nursing management combined with appropriate clinical use ensures that IM olanzapine remains a safe and effective intervention for managing acute agitation and maintaining long-term stability in psychiatric patients.

Opioid use disorder is associated with persistent molecular and cellular changes in the brain, leading to compulsive drug-seeking behaviors. This study aimed to evaluate the effects of olanzapine (OLZ), a D2-like dopamine receptor (D2R) antagonist, on morphine dependence using the conditioned place preference (CPP) model. Morphine-induced CPP was established by subcutaneous (sc) administration of morphine (5mg/kg) for three consecutive days. OLZ at doses of 1.5, 3, and 4.5mg/kg was administered intraperitoneally (ip) during different phases of CPP: acquisition, expression, and extinction. Behavioral assessments included measurement of conditioning scores and locomotor activity. D2R protein expression in the hippocampus (HIP) was evaluated using western blotting. OLZ reduced both acquisition and expression of morphine-induced CPP in a dose-dependent manner. Additionally, OLZ facilitated extinction by shortening the duration of the extinction phase. Western blot analysis showed a significant reduction in D2R protein expression in the expression and extinction phases in the OLZ-treated groups compared to the morphine-only group. Importantly, effective doses of OLZ did not impair locomotor activity. OLZ attenuates morphine-induced CPP and downregulates D2R expression in the HIP without affecting general locomotor function. These findings suggest a potential therapeutic role for OLZ in the management of opioid-related behaviors. Further research is needed to determine its clinical relevance.

Simple, accurate, and precise UV spectrophotometric methods were developed and validated for the simultaneous determination of olanzapine (OLA) and fluoxetine (FLU) in bulk powders and combined pharmaceutical formulations without prior separation steps. The methods employed advanced mathematical manipulation techniques using both the Constant Multiplication method (CM) coupled with Spectrum Subtraction (SS) and the Factorized Zero-Order method (FZM), which was also coupled with SS. These approaches utilized normalized and factorized spectra, respectively, to resolve the overlapping spectral profiles of the two drugs. Unlike conventional methods reported in the literature, such as derivative spectrophotometry, our approach enabled the extraction of each component in its original zero-order form, exhibiting spectral features identical to those of pure standards, which enhances accuracy and precision. A direct comparative evaluation of CM–SS and FZM–SS is presented, highlighting their respective analytical merits. The proposed methods demonstrated linearity over concentration ranges of 1.5–14 µg/mL and 3.5–35 µg/mL for OLA and FLU, respectively, with limits of detection of 0.15 µg/mL (OLA) and 0.38 µg/mL (FLU), and limits of quantification of 0.47 µg/mL (OLA) and 1.15 µg/mL (FLU), confirming the high sensitivity of the methods. They were successfully applied for the simultaneous determination of OLA and FLU in synthetic mixtures and in their combined dosage form with excellent accuracy and precision. Furthermore, the environmental and practical merits of the methods were evaluated through the principles of Green Analytical Chemistry (GAC) and White Analytical Chemistry (WAC). The greenness of the proposed spectrophotometric method was evaluated by the Analytical Greenness Metric (AGREE). The overall method performance, including validation efficiency, ecological impact, and practicality, was systematically evaluated using the RGB-based WAC approach.

Abstract Background: Despite guideline-based antiemetics, refractory nausea remains common and significantly impairs quality of life (QOL) in patients receiving emetogenic chemotherapy. In this secondary analysis of a Phase III NCORP trial, we assessed whether olanzapine’s (OLZ) effects on QOL were mediated by reductions in nausea, using a moderated mediation model. We also evaluated subgroup differences by chemotherapy emetogenicity (HEC vs. MEC). Methods: In the parent RCT (NCT03367572), 1,363 chemotherapy-naïve breast cancer patients were screened across 21 NCORP sites while initiating highly (HEC) or moderately emetogenic chemotherapy (MEC). All received ASCO-recommended antiemetics. Three timepoints were defined: baseline prior to chemotherapy initiation (T1); immediately following Cycle 1 and prior to randomization (T2); and immediately prior to Cycle 2, post-randomization (T3). After Cycle 1 (T2), 310 patients with moderate nausea (≥3 on a 1-7 scale) were randomized 1:1:1 to receive olanzapine (OLZ), prochlorperazine (PC), or placebo, in addition to the standard regimen. This secondary analysis focused on the OLZ arm due to its superior QOL effects in the parent trial. Nausea was assessed using a 4-day home diary, with the maximum reported score across all diary entries used for analysis. QOL was measured via the FACT-G. We applied structural equation modeling (SEM) to evaluate whether OLZ’s effect on QOL at T3 was mediated by reductions in nausea, with moderation by time and treatment. Subscale analyses emphasized physical well-being (PWB). Clinically meaningful changes were defined as ≥5 points for FACT-G and ≥2 for subscales. Bonferroni correction (α = 0.00625) adjusted for multiple comparisons. Results: OLZ significantly improved QOL at T3, with 50.5% of the total FACT-G effect (Mean Difference [MD] = 4.67; p=0.002) mediated by reduced nausea (MD=2.36; p=0.001). In the HEC subgroup, the total FACT-G improvement was clinically meaningful (MD=6.50; p=0.001), with 3.82 points (58.8%) mediated (p<0.001). For PWB, OLZ led to a 2.53-point increase (p=0.001), with 59.4% (1.50 points) mediated by nausea reduction (p<0.001); in HEC patients, PWB increased by 3.20 points, with 72.2% (2.30 points) mediated (p<0.001). No significant effects were observed in the MEC group. A significant time-by-arm interaction (p<0.001) indicated greater improvement in nausea for OLZ compared to other arms between T2 and T3, the period during which OLZ was administered. Conclusions: In this secondary analysis, over half of OLZ’s benefit on overall QOL, and up to 72% of its benefit on physical well-being, was mediated by reductions in nausea. While effects were most pronounced in patients receiving HEC, clinically meaningful improvements were also observed in the MEC group, underscoring olanzapine’s broad utility across emetogenic risk levels. These findings highlight the critical role of nausea control in enhancing QOL and patient-reported outcomes, while supporting the integration of OLZ into standard antiemetic regimens for patients undergoing emetogenic chemotherapy. Citation Format: K. Spath, C. Fung, J. Guido, G. Morrow, M. Janelsins, C. Kamen, J. McGuire, L. Mattick, P. Kumar, J. Fukui, D. Doster, L. J. Peppone. Nausea as a Mediator of Olanzapine’s effect on Quality-of-Life Improvement in Patients Receiving Highly or Moderately Emetogenic Chemotherapy Insights from a Phase III NCORP RCT [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD1-09.

BackgroundProphylaxis for chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) is essential. Four-drug antiemetic therapy, consisting of a neurokinin-1 receptor antagonist (NK1RA), a 5-hydroxytryptamine type 3 receptor antagonist (5-HT3RA), dexamethasone (DEX), and olanzapine (OLZ), is currently recommended for HEC. However, the efficacy, optimal dosing schedule, and appropriate dosage of OLZ remain unclear when combined with a highly selective NK1RA, fosnetupitant (FosNTP).ObjectiveThis study aimed to evaluate the efficacy and safety of a four-drug antiemetic regimen including FosNTP and OLZ for prophylaxis of CINV in patients receiving anthracycline-based (neo)adjuvant chemotherapy for early breast cancer (EBC) and to explore outcomes with OLZ dose adjustments in the second cycle.MethodsThis single-institution, prospective observational study will enroll 100 patients with EBC who undergo HEC. All patients will receive a four-drug antiemetic regimen consisting of FosNTP, 5-HT3RA, DEX, and the guideline-recommended dose of OLZ administered orally from days –1 to 4. During the second cycle of treatment, OLZ dosing may be adjusted based on tolerability and patient preference. The primary endpoint is the proportion of patients who experienced no nausea during the overall phase (0‐120 h) of the first cycle, as assessed using the daily visual analog scale. A sample size of 86 was calculated to assess the efficacy of the four-drug antiemetic regimen, including OLZ, assuming an expected no nausea rate of 42%, a threshold no nausea rate of 27% based on historical data, 90% power, and a 1-sided significance level of 5.0%. A single-sample z-test with a normal approximation will be used for the analyses.ResultsThis study was approved by the Ethics Committee of the National Hospital Organization Kyushu Cancer Center, and participant recruitment and data collection commenced in May 2024. As of September 2025, approximately 70 participants have been recruited. Data collection is expected to continue until April 2026, and both data collection and analyses are anticipated to be completed in 2027.ConclusionsThis study will provide real-world evidence on the effectiveness and safety of a four-drug antiemetic regimen, including FosNTP and OLZ, in patients receiving anthracycline-based HEC and may inform optimal OLZ dosing strategies.

Drugs are an important cause of non-alcoholic fatty liver disease (NAFLD), and olanzapine is the main drug that leads to NAFLD. However, the mechanism by which this drug causes NAFLD is still unclear at present. We previously found that dapagliflozin had certain intervention effect on patients with NAFLD. This study aimed to explore the mechanism of olanzapine-induced NAFLD and the intervention effect of dapagliflozin. Twenty-four female wistar rats were classified into control (NC) group, olanzapine (OLA) group, and dapagliflozin intervention (DAP) group for a total of 12weeks of intervention. This study explored the specific mechanism of olanzapine-induced NAFLD and potential treatment method from dapagliflozin through transcriptomics, molecular biology, and pathological staining methods in animal models. The transcriptome and immunohistochemistry studies of the intestine and liver revealed the high expression of GLUT5 in both tissues (P < 0.01). Olanzapine induced gut-liver axis injury via GLUT5/AMPK/mTOR (P < 0.05 or P < 0.01). Dapagliflozin reversed GLUT5/AMPK/mTOR to improve intestinal barrier injury, NAFLD and hepatic fibrosis (P < 0.05 or P < 0.01). The study discovered for the first time that GLUT5/AMPK/mTOR drived gut-liver axis injury mediating olanzapine-induced NAFLD and dapagliflozin intervention could reverse GLUT5/AMPK/mTOR-driven gut-liver axis injury ameliorating olanzapine-induced NAFLD. This provided a new understanding of the occurrence of olanzapine-induced NAFLD and offered a reference plan for its clinical intervention.

Simulation-based learning replicates real clinical events to provide an interactive learning experience. This allows training doctors to develop skills to manage complex scenarios or emergencies in a safe and containing environment. Many house officers report a lack of confidence in managing emergencies on a psychiatric ward. This study evaluates whether simulation-based learning provided at the start of the psychiatric placement increases the confidence of house officers managing emergencies in a psychiatric setting. Simulation-based learning was developed and implemented for house officers beginning their psychiatric rotation. Three scenarios were developed with psychiatric trainees. These were managing a non-fatal hanging, non-suicidal self-injury, and olanzapine pamoate post-injection syndrome. Training was evaluated with a mixed methods approach. Twenty-three house officers participated in simulation-based learning. After completing the training, participants were significantly more confident managing olanzapine pamoate post-injection syndrome (p < 0.001), non-suicidal self-injury (p < 0.001), and a non-fatal hanging (p < 0.001). Participants reported that simulations were effective because the scenarios were realistic, and the simulation was an immersive experience. They valued the opportunity to practice with the equipment and the focus on both physical and psychological components in the scenarios. The experience was more impactful because simulations were done alongside peers in a safe and contained training environment. Simulation-based learning was acceptable and increased the confidence of house officers managing emergencies in a psychiatric setting. Simulation-based learning can potentially improve the quality of care provided in psychiatric hospitals and the preparedness of new doctors entering these work environments.

Olanzapine (OLZ), haloperidol (HALP), and their combination, are widely used antipsychotics; the majority of studies focuses on their therapeutic efficacy, leaving significant gaps in understanding their systemic impacts. Hence, the present study was conducted to investigate their systemic, metabolic, and inflammatory impact on schizophrenic patients. A total of 75 schizophrenic patients and 25 healthy volunteers were involved and monitored over a six-month period. Study groups were as follow; normal control, OLZ (20 mg/day), HALP (10 mg/day), and OLZ (20 mg/day) + HALP (5 mg/day). The parameters of metabolic, inflammatory, and neuronal transmitters, along with cardiovascular, hepatic, and renal functions were determined. In this study we found that OLZ and HALP produced a noticeable decrease in potassium and chloride ions, while their combination decreased potassium, chloride and calcium. OLZ and OLZ + HALP significantly prolonged QTc, while OLZ and HALP individual administration increased SBP and CK-MP respectively. HbA1C levels not significantly affected by tested drugs, while OLZ produced a significant reduction in LDL and HDL levels, while OLZ + HALP modestly decreased LDL levels. renal assessment revealed a significant increase in both creatinine and urea concentrations in the OLZ + HALP group compared to other groups, whereas hepatic function showed no significant differences between the treated groups. OLZ significantly decreased total bilirubin and increased ALP activity, while HALP significantly reduced total and direct bilirubin levels. OLZ and OLZ + HALP produced a significant increase in body weight and waist circumference, which was not found in HALP-treated patients. Schizophrenic patients had reduced dopamine levels that was not significantly affect by OLZ or OLZ + HALP administration, while HALP administration normalized dopamine levels. Schizophrenic patients had significantly higher levels of serotonin compared to controls, that was normalized by our tested drugs. Ghrelin levels were significantly lower in schizophrenic patients, and it was significantly increased by HALP administration. Leptin hormone significantly elevated in schizophrenics, and was significantly decreased by HALP administration. Schizophrenic patients exhibited markedly elevated levels of IL-17, IL-6, and TNF-α, that dramatically decreased by tested drugs, and the combined regimen showed the highest impact. This study provides valuable insights into the systemic, metabolic, and inflammatory effects of tested drugs, support the individualized therapeutic approaches in schizophrenic patients to optimize clinical outcomes and minimizing long-term systemic risks.

BackgroundChronic kidney disease (CKD) is associated with an increased risk of neuropsychiatric disorders, cognitive decline, dementia due to the release of cytokines and chemokines, production of reactive oxygen species, and the generation of trophic factors. The second‐generation antipsychotic olanzapine (OLN) has been studied for its neuroprotective and antioxidant properties that may enhance cognitive function. However, limited research has explored the interaction between brain cytokines and kidney biomarkers, which could contribute to pathological conditions. This study aimed to assess the effects of OLN on cognitive function, oxidative stress, and the relationship between brain and kidney markers in mice with aluminum chloride (AlCl₃)‐induced memory impairment.MethodTwenty‐five male mice (20‐30 g) were randomly assigned to five groups (n = 5 each). Group 1 served as the control, receiving only distilled water (10 ml/kg). Group 2 received AlCl₃ (100 mg/kg). Groups 3 and 4 were pre‐treated with OLN (0.5 mg/kg and 1.0 mg/kg, respectively) one hour prior to AlCl₃ administration. Group 5 was pre‐treated with Donepezil (1 mg/kg). All treatments were administered orally for seven consecutive days. On the final day, neurobehavioral tests, including the Y maze and open field tests, were conducted to evaluate memory impairment. The mice were then euthanized; their brain and kidney tissues were analyzed for tumor necrosis factor‐alpha (TNF‐α), antioxidant markers, urea, and total protein levels, along with histopathological examination of the hippocampus and prefrontal cortex.ResultBoth doses of OLN significantly improved cognitive function in the Y maze and open field tests, reduced oxidative stress by decreasing malondialdehyde and increasing SOD, catalase, and glutathione levels, and lowered brain TNF‐α levels. Histopathological assessments indicated that OLN reduced neurodegeneration in the hippocampus and prefrontal cortex. There is also decreased kidney urea and increased protein concentration.ConclusionOLN significantly improves memory and antioxidant levels while reducing cytokine levels, although its effects on kidney function are limited. These results underscore the intricate relationship between OLN, cognitive function, and renal health.

Olanzapine (OLZ), a second-generation antipsychotic, is associated with the development of metabolic syndrome with unclear underlying pathophysiologic mechanisms. Oxytocin (OT) influences feeding, lipid, and glucose metabolism. This study investigates whether dysfunction in the oxytocinergic system contributes to the development of olanzapine-induced metabolic syndrome. Twenty five (25) female Sprague-Dawley rats were housed under standard conditions and studied over 12 weeks. During the first 6-week induction phase, rats were randomized into 3 groups: normal control (vehicle treatment; normal saline; n = 5), low dose (4 mg/kg olanzapine [OLZ]; n = 5), and high dose (8 mg/kg OLZ; n = 15). In the last 6-week treatment phase, the high dose group was re-randomized into 3 groups: negative control (8 mg/kg OLZ; n = 5), positive control (8 mg/kg OLZ + 500 mg/kg metformin; n = 5), and test group (8 mg/kg OLZ + 1 mg/kg oxytocin [OT]; n = 5). The normal control and low dose groups continued unchanged. Body weight, food intake, glucose levels, OGTT, lipid profile, visceral fat, hepatic index, hepatic triglycerides, and steatosis were assessed. At induction end, high-dose OLZ increased food intake (179 ± 5 g), body weight (239 ± 3 g), blood glucose (7.8 ± 0.3 mmol/L), and impaired glucose tolerance (846 ± 25 mmol/L·min) compared to controls (p < 0.0001). Post-treatment, the test group displayed reduced food intake (163 ± 2 g vs. 197 ± 6 g), body weight (297 ± 2 g vs. 376 ± 6 g), blood glucose (5.8 ± 0.3 mmol/L vs. 9.8 ± 0.2 mmol/L), and improved glucose tolerance (711 ± 14 vs. 853 ± 9 mmol/L·min) compared to negative controls (p < 0.0001). LDL-C, total cholesterol, serum and hepatic triglycerides, visceral adipose, and hepatic mass and steatosis were also significantly decreased in the test group compared to negative control group (p < 0.01). OLZ-induced metabolic abnormalities were mitigated by oxytocin, indicating that the oxytocinergic system hypofunction may be implicated in its pathophysiology. These results highlight OT's therapeutic potential and call for further clinical research to explore its role in the management of antipsychotic-induced metabolic syndrome.

352 Background: Refractory nausea remains a significant and distressing symptom for cancer patients despite guideline-based antiemetic regimens, often severely impacting quality of life (QOL). This analysis determined the extent to which reductions in nausea from olanzapine (OLZ) contribute to improvements in QOL, using moderated mediation analysis to quantify this relationship. Methods: The URCC NCORP Research Base, in collaboration with 21 NCORP practices, screened 1,363 chemotherapy-naïve breast cancer patients starting a moderate to highly emetogenic chemotherapy regimen for this Phase III RCT (NCT03367572), with all patients receiving ASCO-recommended antiemetics. Three timepoints were defined: baseline at time 0; screening during the first chemotherapy cycle at time 1; and randomization at the second cycle (time 2) for patients meeting eligibility criteria. Patients reporting moderate nausea (≥3 on a 1-7 scale) during Cycle 1 and willing to continue were randomized (1:1:1) into three arms each receiving the ASCO regimen (n = 310): 1 OLZ, 2 prochlorperazine (PC), or 3 placebo. The analysis focused on OLZ as it had the largest effect size on QOL. Nausea was evaluated using a four-day home diary (4x daily); QOL was measured with the FACT-G. Moderated mediation analysis using a structural equation model estimated total and indirect effects, and proportion meditated by nausea between OLZ and QOL. Analyses were done separately for FACT-G and its subscales. Changes of ~5 points in FACT-G and 2 points in subscales were considered clinically meaningful. Time moderation was evaluated with interactions between time and arm. A Bonferroni correction (α = 0.00625) adjusted for multiple testing. Results: Nausea significantly mediated the relationship between OLZ and QOL, with 50.5% of the total effect at time 2 attributable to decreased nausea (p = 0.001). The total effect of OLZ on FACT-G was an increase of 4.67 points (p = 0.002), a clinically meaningful improvement, with 2.36 points mediated by decreased nausea (p = 0.001). For the PWB subscale, the total effect was an increase of 2.53 points (p = 0.001), with 1.50 points mediated by decreased nausea (p &lt; 0.001), representing 59.4% of the total effect at time 2 (p &lt; 0.001). A significant time-by-arm interaction was observed in both the FACT-G and PWB models (p &lt; 0.001), highlighting a time-dependent relationship between nausea and QOL improvements. Conclusions: Effective nausea control is a key mediator of OLZ’s impact on QOL, with over 50% of the improvement in FACT-G and nearly 60% in PWB attributable to decreased nausea —both statistically significant, PWB with clinical significance, and FACT-G approaching clinical significance. These findings highlight the critical role of effective nausea management in enhancing QOL and support the integration of OLZ into routine clinical practice as a valuable tool for improving patient outcomes. Clinical trial information: NCT03367572 .

Harnessing dicarboxylate-based salts for enhancing the performance of amorphous solid dispersions: The case of olanzapine.

Background/Objectives: The clinical impact of antipsychotics on the human body remains inadequately investigated, hence we aimed to compere the effects olanzapine (OLZ) and Clozapine (CLZ) on different body systems. Methods: 48 patients and 24 healthy individuals were involved, and followed over six months. PANSS, metabolic, cardiovascular, inflammatory, and neuronal transmitter parameters were determined. Results: No significant difference was found between the effects of the two drugs on blood mineral and cardiovascular parameters, except for CK-MB, which showed a greater increase in the OLZ group than in the CLZ group. Both drugs increased the lipid profile and HbA1C levels, with the effect of CLZ being more prominent. Both drugs increased the patients’ body weights, with no significant difference between their effects. Regarding renal and hepatic functions, OLZ had a more notable effect on creatinine and albumin levels than CLZ, while AST and ALT showed markedly greater increases in the CLZ-treated group than in the OLZ-treated group. Regarding the effects on neurotransmitters and inflammatory mediators, both drugs increased serotonin and ghrelin levels, in addition to decreasing leptin concentrations, and decreased the inflammatory mediators IL-1β, IL-6, and –TNF-α, with the effect of OLZ being more prominent. Regarding therapeutic efficacy, CLZ was more effective at reducing general and negative symptoms than OLZ. Conclusions: The present study revealed that CLZ had a greater impact on metabolic parameters and better therapeutic efficacy in attenuating both general and negative symptoms, whereas OLZ had more detectable anti-inflammatory effects, aid determining the appropriate treatment for schizophrenic patients.

Developing a rapid, simple method to detect psychiatric drug concentrations is essential, as it facilitates long-term monitoring of treatment efficacy and is critical for managing drug poisoning in clinical settings due to abuse or accidental overdose. Conventional laboratory-based assays used for monitoring psychiatric medications often demonstrate prolonged processing times, leading to considerable delays in adjusting treatment regimens. To address this, this study introduced a point-of-care testing (POCT) approach using a miniature mass spectrometer, which allows for rapid and precise measurement of three psychiatric drugs including carbamazepine (CBZ), quetiapine (QTP), and olanzapine (OLZ) in human plasma and whole blood. Quantification is achieved through the use of paper capillary spray combined with miniature mass spectrometry, within the clinically relevant concentration range for three drugs. Only a minimal amount of bodily fluid (50µl) is required, and the assay turnaround time is less than 2min. Good linear relationships are established between mass spectrometry (MS)/MS responses and concentration, with correlation coefficients (R2) of no less than 0.99. The limits of detection (LODs) for CBZ, QTP, and OLZ were 0.05µg/ml, 5ng/ml, and 5ng/ml, respectively. Satisfactory precision with relative standard deviations (RSDs) below 21.06% was obtained. Additionally, the developed method was successfully applied to determine the concentrations of psychiatric drugs in real clinical samples. The strengths of this work lie in its portability, speed, and timeliness of detection, which attributed to the characteristics of the miniature MS used, making it suitable for rapid on-site screening.

Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality, requiring innovative treatment strategies. Olanzapine (OLZ), an atypical antipsychotic, has demonstrated efficacy in promoting weight gain and reducing psychopathological symptoms in adults with AN. However, its efficacy and safety in adolescents remain insufficiently explored. This study assessed the impact of adjunctive OLZ in adolescents with AN during inpatient care, focussing on weight gain, eating disorder pathology, and metabolic safety. A naturalistic, prospective study compared two groups of adolescent inpatients with AN (n=47 each), one receiving standard multidisciplinary care plus OLZ and one receiving standard care alone (Non-OLZ). Weekly weight gain as well as admission-to-discharge changes in body-mass-index, eating disorder symptoms, and metabolic markers were compared between the two cohorts. The OLZ group (∅ 9mg/day) achieved greater weekly weight gain (0.898 vs. 0.677kg, p=0.004) compared to the Non-OLZ group. Both groups showed similar reductions in eating disorder pathology; however, improvements in body dissatisfaction were larger in the Non-OLZ group. Administration of OLZ was associated with significant prolactin level increases. OLZ is a promising adjunctive treatment for adolescents in terms of supporting weight gain during inpatient care. However, psychological effects and possible metabolic risks warrant further study.

Abstract Olanzapine (OLZ) is classified as a typical antipsychotic drug utilized for treatment of schizophrenia, it possesses poor oral bioavailability (60%) due to low solubility and first-pass hepatic metabolism. Hence, the aim of present work is to fabricate and evaluate an olanzapine nanoparticle dissolved microneedles for transdermal delivery to overcome the problems that associated with drug orally, in addition to the ease of administering the medication for schizophrenic patients. Nanoprecipitation method was employed for preparation of olanzapine nanoparticles by using different polymers with various ratios. Nanoparticles were evaluated by several characterization studies such as particle size, polydispersity index(PDI), entrapment efficiency and zeta potential and an in vitro release study. The morphology of nanoparticle was screened by field emission scanning electron microscope (FESEM). Dissolved Microneedle (MN) patch was fabricated by loading of olanzapine nanodispersion into polydimethylsiloxane (PDMS) micromolds cavities, followed by casting the polymeric solution of polyvinylpyrrolidone(PVP-K30) and polyvinyl alcohol (PVA) to form the microneedle matrix, the prepared microneedle patches were evaluated for morphology, mechanical strength, drug content and ex vivo permeation study. The results reveal that olanzapine nanoparticles was in nano-size scale ranged from 70.12nm to 344nm, PDI values range (0.152-0.404), entrapment efficiency ranged from 53.2% to 78.4%, the highest zeta potential value was (-19.01mV) for olanzapine nanoparticle (OLZ-5), that exhibits higher and significant release of drug (P&lt;0.05). FESEM shows spherical shape of nanoparticle with size similar to that obtained by zetasizer. According to the results of nanoparticles, the formula (OLZ-5) considered as optimized formula and utilized for fabrication of microneedle. The results of microneedle fabrication indicate that MN-4 exhibits a sharp needle with good mechanical strength according to texture analysis, high drug content (98.52%), ex vivo permeation study exhibits that MN-4 permeate more effectively through the skin as compared to the simple patch by approximately 5.16 folds. It can be concluded that microneedle patch (MN-4) considered as promising formula to overcome the problems associated with drug orally and could enhance its bioavailability, in addition to improve patient compliance.