Olanzapine Regimen Research Articles

Atypical Antipsychotics and Lithium Induced Neuroleptic Malignant Syndrome associated with Acute Kidney Injury: A Case Report

Neuroleptic Malignant Syndrome (NMS) is a rare but serious adverse reaction to antipsychotic medications. This case report presents a 56-year-old male with bipolar disorder on a regimen of Olanzapine, Clozapine and Lithium carbonate, who developed typical NMS. He had muscle rigidity, hyperthermia, rhabdomyolysis which led to acute kidney injury. Prompt withdrawal of psychotropic medications and administration of supportive therapies was done, yet the patient's condition deteriorated, leading to Multiple Organ Dysfunction Syndrome (MODS) and eventually mortality. This case shows the complexity of managing NMS in the context of polypharmacy emphasizing the need for vigilance when prescribing antipsychotic combinations and the challenges faced in treating NMS, especially when there are associated complications.

A randomized trial evaluating the association between related gene polymorphism and nausea and vomiting induced by cisplatin multi-day chemotherapy

PurposeWe aim to investigate the correlation between gene polymorphisms and cisplatin chemotherapy-induced nausea and vomiting (CINV), which was prevented by olanzapine or aprepitant triple antiemetic regimen.MethodsBefore chemotherapy, the blood samples of 89 malignant tumor patients who received multi-day chemotherapy with cisplatin were collected for sequencing and typing. As there were duplicate patients enrolled in different chemotherapy cycles, there were a total of 190 cases. The patients were divided into two groups randomly, who received the triple antiemetic regimen of olanzapine or aprepitant combined with 5-HT3RA and dexamethasone. The main evaluation indicators were the total protection (TP) rate in the acute phase (0–24 h), the delayed phase (25–120 h) and the overall phase (0-120 h).ResultsUnivariate analysis was performed on genetic loci that reached H-W balance with TP. In the olanzapine group, increased TP in the acute phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. In the aprepitant group, increased TP in the acute phase was associated with the MTHFR rs1801131 TT (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1062613 CC (P < 0.05) genetype ect. Multivariate Logistic regression analysis showed that HTR3B rs7943062GG (P < 0.05) genotype etc. were correlated with increased TP in the delayed phase. MTHFR rs1801131TT genotype was associated with increased TP in the acute phase (P < 0.05) and delayed phase (P < 0.05).ConclusionThis study found that gene polymorphisms, including HTR3B (rs1062613, rs1176719, rs2276303), HTR3B (rs45460698, rs7943062), HTR3C (rs6766410), ERCC1 (rs3212986), ERCC4 (rs744154) and MTHFR(rs1801131), may be independent prognostic factors for CINV.

Guideline-concordant use of olanzapine as part of a 4-drug antiemetic regimen for high emetic risk chemotherapy across the state of Michigan.

6519 Background: Chemotherapy-induced nausea and vomiting (CINV) is a feared side effect of cancer treatment. If not adequately controlled, CINV can negatively affect both quality of life and increase the costs of care. Clinical practice guidelines from both ASCO and NCCN recommend inclusion of olanzapine as part of a 4-drug antiemetic regimen in patients receiving high emetic risk chemotherapy (HEC). Uptake of olanzapine has been low, however, in part due to oncologists’ lack of familiarity with the medication, lack of awareness or agreement with the guidelines, and lack of olanzapine inclusion on prepopulated order sets. Current labeling of olanzapine as an antipsychotic poses an additional barrier. The purpose of this project was to increase guideline-concordant prescribing of olanzapine as part of a 4-drug antiemetic regimen in patients receiving HEC in practices that are part of the Michigan Oncology Quality Consortium (MOQC), a physician-led consortium of nearly 90% of oncologists in Michigan. Methods: In 2019, MOQC began measuring guideline-concordant HEC prophylaxis with a 4-drug regimen of olanzapine added to corticosteroids, a 5HT3RA, and an NK1RA as part of its measure set. A quality improvement intervention was initiated that consisted of 1) dissemination of baseline measure performance and regular reporting of practice and state-level performance to MOQC practices, 2) information support through sharing of guidelines at biannual meetings (2019, 2022) and state-wide CINV education to improve prescriber knowledge and beliefs and support the practices in updating prepopulated antiemetic order sets, and 3) addition of value-based reimbursement in 2021 to encourage practice change. Measure performance was assessed using ASCO’s Quality Oncology Practice Initiative (QOPI) program. Results: The patient sample included 5,703 patients. MOQC practices increased the guideline-concordant prescribing of olanzapine as part of a 4-drug antiemetic regimen in patients receiving HEC round over round from R1 2019 to R1 2022 (p&lt;0.0001). Conclusions: MOQC has facilitated increased use of olanzapine as part of a 4-drug antiemetic regimen in patients receiving HEC through practice education, reporting, and value-based reimbursement. Ongoing work will focus on practices with low uptake and on demonstrating the impact of this important practice change on patient outcomes. [Table: see text]

Cost-effectiveness analysis of olanzapine in four-drug antiemetic therapy in Japanese patients treated with highly emetogenic cisplatin-containing chemotherapy

BackgroundOlanzapine has been shown to have an additive effect on the three-drug antiemetic therapy consisting of aprepitant, palonosetron, and dexamethasone, in a highly emetogenic cisplatin-containing chemotherapy. Although olanzapine may be more economical than aprepitant or palonosetron, an adequate cost-efficacy analysis has not been conducted.MethodsWe conducted a cost-utility analysis to evaluate the cost-effectiveness of olanzapine use in four-drug antiemetic therapy among Japanese patients. We simulated model patients treated with highly emetogenic cisplatin-containing chemotherapy and developed a decision-analytical model of patients receiving triple antiemetic therapy with or without olanzapine in an inpatient setting. The cost and probabilities of each treatment were calculated from the perspective of the Japanese healthcare payer. The probabilities, utility value, and other costs were obtained from published sources. One-way and probabilistic sensitivity analyses were conducted to examine the influence of each parameter on the model and the robustness of a base-case analysis. Threshold analysis was conducted to determine the cost of olanzapine that would make the incremental cost-effectiveness ratio (ICER) equivalent to the threshold ICER). The threshold incremental cost-effectiveness ratio was set at 5 million Japanese Yen (JPY) per quality-adjusted life-year (QALY) gained.ResultsThe cost was 10,238 JPY in the olanzapine regimen and 9719 JPY in the non-olanzapine regimen. The QALY gained were 0.01065 QALYs and 0.01029 QALYs in the olanzapine and non-olanzapine regimen, respectively. The incremental cost of the olanzapine regimen relative to the non-olanzapine regimen was 519 JPY, and the incremental QALYs were 0.00036 QALY, resulting in an ICER of 1,428,675 JPY per QALY gained. In the one-way sensitivity analysis, the results were most sensitive to the utility value of incomplete control. The probabilistic sensitivity analysis revealed the probability that the ICER was below the willingness-to-pay, and the incremental QALYs was positive was 96.2%. The calculated cost of olanzapine per 5 mg that would make the incremental cost-effectiveness ratio equivalent to the threshold incremental cost-effectiveness ratio was calculated to be 475 JPY.ConclusionsOlanzapine was cost-effective in the four-drug antiemetic therapy for Japanese patients treated with highly emetogenic cisplatin-containing chemotherapy.

Short-course olanzapine to prevent delayed emesis following carboplatin/paclitaxel for gynecologic cancer: a randomised study.

To explore efficacy of short-course olanzapine with or without low-dose dexamethasone for prevention of delayed emesis in gynecologic cancer patients receiving carboplatin/paclitaxel. This was a prospective study in 81 chemo-naive patients receiving 0.25 mg intravenous palonosetron, 16 mg dexamethasone, and 10 mg oral olanzapine before chemotherapy. On days 2 and 3, patients randomly received 10 mg olanzapine (arm A; n=27), 10 mg olanzapine plus 4 mg dexamethasone (arm B; n=27), or 8 mg dexamethasone (reference arm C; n=27). The primary endpoint was total control (TC; no vomiting, no rescue antiemetics, and no nausea) on days 2-5, using a diary. Secondary endpoints included proportion of patients with no emesis impact on daily life using the Functional Living Index-Emesis (FLIE) questionnaire, and patient's satisfaction with antiemetic coverage. Fifty-two percent of patients in arm A (P=0.406), 59% in arm B (P=0.779), and 67% in arm C had a delayed TC. Secondary analyses showed no significant difference across arms in any efficacy endpoint. FLIE scores as well as mean satisfaction scores were similar across arms. In this exploratory study with a small sample size, we did not find any clue about better control of delayed emesis with either olanzapine regimen in gynecologic cancer patients treated with carboplatin/paclitaxel and receiving the same prophylaxis for acute emesis.

Olanzapine for Chemotherapy-Induced Nausea and Vomiting (CINV) Prophylaxis in Patients Receiving High-Dose Chemotherapy for Autologous Hematopoietic Stem Cell Transplantation (ASCT)

Introduction Olanzapine has demonstrated clinical efficacy for CINV prophylaxis. Efficacy and safety of olanzapine for CINV prophylaxis in patients receiving high-dose chemotherapy as conditioning regimen for HSCT is not established. Objective The primary objective is to compare efficacy and safety of olanzapine versus fosaprepitant for CINV prophylaxis in patients receiving high-dose chemotherapy for ASCT. Methods A single-center, retrospective analysis evaluated consecutive patients who received high-dose melphalan or BEAM for ASCT from June 2016 to September 2018. April 2017 onwards, we switched CINV prophylaxis to olanzapine, replacing fosaprepitant. In this analysis, outcomes of an olanzapine regimen combined with ondansetron and dexamethasone (OOD) were compared with fosaprepitant combined with ondansetron and dexamethasone (FOD). Assessment period for CINV was defined as acute phase (chemotherapy days) and delayed phase (within 5 days of chemotherapy completion). The primary endpoint is the proportion of days requiring rescue CINV medications during the assessment period. Secondary endpoints include number of rescue medication doses required during the acute and delayed phases, time to neutrophil engraftment (TTNE), and length of stay (LOS). A cost-effectiveness analysis is being performed. Results A total of 154 patients were evaluated (FOD = 83 and OOD = 71). Patient demographics were similar in both groups, except that patients in the OOD cohort were older (median age 63 vs. 55 years; p = 0.0002). Patients received the following conditioning regimens: melphalan 140 mg/m2 (FOD = 10; OOD = 21), melphalan 200 mg/m2 (FOD = 28; OOD = 44), BEAM (FOD = 45; OOD = 6). In the acute phase, 10% of FOD patients required rescue CINV medications on at least 50% of days while approximately 3% of OOD patients required rescue medications on any day (p = 0.006). In the delayed phase, the median proportion of days requiring rescue CINV medications was significantly lower with OOD (60% vs. 20%; p Conclusion Olanzapine-based CINV prophylaxis was significantly superior to fosaprepitant for the proportion of days requiring rescue CINV medications.

Population pharmacokinetics analysis of olanzapine for Chinese psychotic patients based on clinical therapeutic drug monitoring data with assistance of meta-analysis.

The aim of this study was to build an eligible population pharmacokinetic (PK) model for olanzapine in Chinese psychotic patients based on therapeutic drug monitoring (TDM) data, with assistance of meta-analysis, to facilitate individualized therapy. Population PK analysis for olanzapine was performed using NONMEM software (version 7.3.0). TDM data were collected from Guangzhou Brain Hospital (China). Because of the limitations of TDM data, model-based meta-analysis was performed to construct a structural model to assist the modeling of TDM data as prior estimates. After analyzing related covariates, a simulation was performed to predict concentrations for different types of patients under common dose regimens. A two-compartment model with first-order absorption and elimination was developed for olanzapine oral tablets, based on 23 articles with 390 data points. The model was then applied to the TDM data. Gender and smoking habits were found to be significant covariates that influence the clearance of olanzapine. To achieve a blood concentration of 20ng/mL (the lower boundary of the recommended therapeutic range), simulation results indicated that the dose regimen of olanzapine should be 5mg BID (twice a day), ≥ 5mg QD (every day) plus 10mg QN (every night), or >10mg BID for female nonsmokers, male nonsmokers and male smokers, respectively. The population PK model, built using meta-analysis, could facilitate the modeling of TDM data collected from Chinese psychotic patients. The factors that significantly influence olanzapine disposition were determined and the final model could be used for individualized treatment.

A modified olanzapine regimen for the prevention of chemotherapy-induced nausea and vomiting.

At Kaiser Permanente Antioch and Walnut Creek Cancer Centers, a modified olanzapine regimen is used to prevent chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC). To determine if an olanzapine, ondansetron, dexamethasone (OOD) regimen is noninferior to a fosaprepitant, ondansetron, dexamethasone (FOD) regimen in preventing CINV in patients receiving HEC. This retrospective cohort study compared the rates of CINV in patients who were treated with HEC and received either the OOD or FOD regimen. Electronic medical records were assessed for documented reports of CINV. 148 patients were included in this study. Complete response (CR), defined as no emesis after Cycle 1 of HEC, in patients receiving the OOD regimen was 95.7% in the acute phase, 94.3% in the delayed phase, and 92.9% overall. CR in patients receiving the FOD regimen was 98.7% in the acute phase, 89.7% in the delayed phase, and 89.7% overall. The percentage of patients who had no nausea on the OOD regimen was 87.1 in the acute phase, 75.5 in the delayed phase, and 71.4 overall, compared with 78.2 in the acute phase, 62.8 in the delayed phase, and 62.7 overall in patients on the FOD regimen. This study was limited by its retrospective, nonrandomized design, and short follow-up period. This study did not assess adverse effects from the antiemetic regimens. A modified olanzapine regimen is noninferior to a standard fosaprepitant regimen in regard to CR in showing improved control of CINV. In addition, the use of the olanzapine regimen reduces patient exposure to corticosteroids and the risk of associated side effects, and it is significantly more cost effective, compared with the fosaprepitant regimen.

Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC): Alliance A221301, a randomized, double-blind, placebo-controlled trial.

176 Background: The purpose of the study was to determine the effectiveness of olanzapine (OLN) for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC). Methods: A randomized, double-blind, phase III trial was performed in chemotherapy-naïve patients receiving cisplatin, &gt; 70 mg/m2, or cyclophosphamide-anthracycline-based chemotherapy, comparing OLN to placebo in combination with aprepitant (APR), a 5-HT3 receptor antagonist (5-HT3), and dexamethasone (DEX). The OLN regimen was 10 mg of oral OLN, 125 mg APR, a 5-HT3, and oral DEX 12 mg pre-chemotherapy, day 1, and 10 mg/day of oral OLN and 8 mg DEX on days 2-4 post-chemotherapy plus 80 mg APR on days 2, 3 post-chemotherapy. The placebo (PLA) regimen was oral placebo, pre-chemotherapy, day 1, and on days 2-4 post-chemotherapy; the APR, 5-HT3, and DEX pre- and post-chemotherapy were identical to that used in the OLN regimen. Fosaprepitant (150 mg IV), day 1 was allowed for substitution for the oral aprepitant. Palonosetron, ondansetron, or granisetron were the permitted 5-HT3 options. Nausea was measured on a 0-10 visual analogue scale, with 0 being “no nausea at all” and 10 being “nausea as bad as it can be”. No nausea was the primary endpoint and, complete response (no emesis and no use of rescue medications) was a secondary endpoint. Results: 401 patients (202 OLN, 199 PLA) were enrolled in the study. The proportion of patients who had no nausea was significantly greater for the OLN regimen compared to the PLA regimen for the acute period (24h post-chemotherapy) (74% vs. 45%, p &lt; 0.0006), for the delayed period ( 24-120 h post-chemotherapy) (43% vs. 26%, p &lt; 0.0006), and for the overall period (0-120 h) (39% vs. 22%, p &lt; 0.0006). Complete response was significantly improved for the OLN patients compared to PLA patients for the acute (85% vs. 65%, p &lt; 0.0001), the delayed (67% vs. 53%, p &lt; 0.0078), and the overall periods (64% vs. 41%, p &lt; 0.0001). There were no grade 3 or 4 toxicities. Conclusions: No nausea, the primary endpoint, and complete response, a secondary endpoint, were significantly improved with OLN, compared to PLA. Clinical trial information: NCT02116530.

Role of Omega-3 fatty acids in preventing metabolic disturbances in patients on olanzapine plus either sodium valproate or lithium: a randomized double-blind placebo-controlled trial

BackgroundMetabolic and cardiovascular side effects have been noted with the use of second generation antipsychotics (SGAs) and mood stabilizers. Since Omega-3 fatty acids have been known to prevent some cardiovascular risks, this preliminary study was designed to evaluate the cardiovascular benefits of omega-3 when added to the combinations of olanzapine with mood stabilizers.MethodsThis study was a randomized, double-blind, placebo-controlled, within-subject trial in adult psychiatric patients who were receiving olanzapine combined with lithium (Li) or valproate sodium (VPA). Omega-3 as fish oil with less than 1 g/day of EPA/DHA or its placebo was added to patients’ olanzapine and mood stabilizer regimens for 6 weeks. Metabolic parameters including anthropometric variables, lipid profile, metabolic syndrome indices, C-reactive protein, fibrinogen and lipoprotein (a) [(Lp) (a)] were assessed for participants.ResultsForty one participants completed this study; 20 patients received omega-3 and 21 patients received placebo, added to their regimen of SGA and mood stabilizer. Omega-3 addition did not modulate anthropometric, metabolic syndrome and lipid parameter changes in 6 weeks. However, fibrinogen levels significantly decreased, Lp (a) did not increase and non-high-density lipoprotein cholesterol (non-HDL-C) did not go beyond its target level after omega-3 supplementation. Additionally, a significant inter-group effect was noted for Lp(a).ConclusionsThis study suggests that use of short-term omega-3 supplementation added to a combined regimen of olanzapine and mood stabilizer may have a small modulating effect on some cardiovascular risk factors. Trials in longer periods of time and with larger number of patients are needed to further evaluate the effects of omega-3 supplements on preventing cardiovascular risk factors.This trial is registered at irct.ir and its Identifier is as following: IRCT138712231764N1

Restarting Clozapine Treatment During Ablation Chemotherapy and Stem Cell Transplant for Hodgkin’s Lymphoma

Back to table of contents Previous article Next article Letters to the EditorFull AccessRestarting Clozapine Treatment During Ablation Chemotherapy and Stem Cell Transplant for Hodgkin’s LymphomaILYSE ROSENBERG D.O.BORIS MEKINULOV M.D.LISA J. COHEN Ph.D.IGOR GALYNKER M.D.,ILYSE ROSENBERG D.O.Search for more papers by this authorBORIS MEKINULOV M.D.Search for more papers by this authorLISA J. COHEN Ph.D.Search for more papers by this authorIGOR GALYNKER M.D.Search for more papers by this author,Published Online:1 Sep 2007https://doi.org/10.1176/appi.ajp.2007.06122021AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To The Editor: We describe an unprecedented case of a patient with bipolar mania who was successfully restarted on clozapine treatment while receiving ablation chemotherapy and an autologous stem cell transplant for Hodgkin’s lymphoma. While a few cases of clozapine use with cancer chemotherapy have been documented (1 – 4) , our case is unique in that a stem cell transplant was involved. “Mr. S” was a 39-year-old white male with a history of bipolar I disorder who presented on a responsive regimen of clozapine (300 mg b.i.d.) and lithium (1800 mg every night), with the occasional addition of benzodiazepines, for 10 years. In February 2006, he was admitted with an exacerbation of his mania, characterized by pressured speech, expansive affect, decreased sleep, and psychomotor agitation. He reported weight loss with episodes of night sweats, pruritic rash, and painless lymph node swelling. Oncology diagnosed the patient with Hodgkin’s lymphoma, nodular sclerosing type. Clozapine was discontinued because of the concern of clozapine-induced agranulocytosis, and the patient was switched to a regimen of olanzapine (30 mg b.i.d.). Lithium and lorazepam were continued.Subsequently, in July 2006 the patient presented with a decompensation of his bipolar disease, despite treatment with olanzapine. Because of his poor response to olanzapine, we considered restarting clozapine, even in the context of active Hodgkin’s lymphoma. The patient was scheduled to receive ablation chemotherapy and a stem cell transplant during that hospitalization. Concerned about the possibility of leukopenia from Hodgkin’s disease treatment, we contacted IVAX pharmaceuticals to determine whether the patient would be eligible for a waiver, because generally clozapine must be immediately discontinued if a patient develops leukopenia (white blood cell count <3000 cell/mm 3 with a satisfactory neutrophil count) or neutropenia (neutrophil count <1500 cell/mm 3 ). It was decided that the benefits outweighed the risks. The waiver was granted and clozapine was restarted. In August 2006 the patient was transferred to another hospital to receive his stem cell transplant. During that treatment, his white blood cell count was 0.1 cell/mm 3 with ANC <0.02. Postprocedure, his white blood cell count was 9.9 cell/mm 3 . He returned to our inpatient unit in September 2006. His white blood cell count since then has remained between 5.5 and 9.9 cell/mm 3 . To our knowledge, this is the first reported case of successful use of clozapine during life-saving ablation chemotherapy and a stem cell transplant. Clozapine should be used with caution due to the risk of leukopenia and the varying degrees in which it affects patients. However, this suggests that in some cases after other options have been exhausted, it is worthwhile to consider restarting patients on clozapine to control acute mania while undergoing stem cell transplant.New York, N.Y.The authors report no competing interests.This letter (doi: 10.1176/appi.ajp.2007.06122021) was accepted for publication in May 2007.

Quetiapine May Be Associated With New-Onset Seizures in Patients With Seizurogenic Conditions

Back to table of contents Previous article Next article LETTERFull AccessQuetiapine May Be Associated With New-Onset Seizures in Patients With Seizurogenic ConditionsIrem Yalug M.D.,Ali Evren Tufan M.D.,Levent Kayaalp M.D.,Irem Yalug M.D.Search for more papers by this author,Ali Evren Tufan M.D.Search for more papers by this author,Levent Kayaalp M.D.Search for more papers by this author,Published Online:1 Jul 2007AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: Quetiapine, although not studied properly, is increasingly prescribed for acute agitations in mental retardation. 1 , 2 We report on new-onset seizures in two patients receiving quetiapine. Case ReportA 16-year-old girl was brought to the hospital by her family with symptoms of a generalized tonic-clonic (GTC) seizure. Ornithine transcarbamylase deficiency (OTCD) and mental retardation were present in past medical history. She had been diagnosed with OTCD 5 years prior, and had successfully managed on a low protein diet until the admission. Because of behavioral instability, a psychiatrist prescribed a regimen of quetiapine, 50 mg/ day 2 days, before the admission. Physical examination was normal except for delayed growth (25th percentile). Neurological examination and laboratory tests on admission were normal. Plasma ammonia was 0.78 μg/ml (normal=0.17 to 0.80 μg/ml).We did not obtain quetiapine concentrations, as the patient had been taking quetiapine for only 2 days, making high serum concentrations unlikely. Echocardiogram (ECG), electroencephalography (EEG) and magnetic resonance imaging (MRI) of the brain were normal. The last EEG was undertaken 1 year before the event and was also normal. Special laboratory studies were done for OTCD, and a plasma amino acid profile was also normal, except for ornithine, which was high: 200 μg/ml (normal=25 to 120 μg/ml). Urine organic acid screening was also normal. From all of the findings above, we suspected that the seizures were triggered by quetiapine and we discontinued the drug. We followed up the patient for 2 weeks and she had no seizures during this period. We put her again on a regimen of quetiapine under strict control to decide whether it was the causative agent. One day after the initiation, she had a GTC seizure and the drug was immediately discontinued. Afterwards, we started her on a regimen of olanzapine. However, after 1 month of treatment with olanzapine, she had a third seizure. After this, we managed her as an outpatient without drugs for the following 11 months, and no seizures were reported.Case ReportA 7-year-old boy who was diagnosed with autism when 3 years old and had been followed up as an outpatient since diagnosis, was admitted to the hospital because of behavioral problems. He was prescribed a regimen of quetiapine, 25 mg/ day. One day after the initiation of treatment he had a GTC seizure. We suspected that quetiapine was the causative agent and discontinued it. There was no history of predisposing factors except for autism and mental retardation. Neurological examination, laboratory tests, ECG, EEG and MRI of the brain were normal. He was followed up without any drug therapy and no seizure was reported. After 1 month of observation, we started him on a regimen of risperidone and managed him as an outpatient for the following 18 months.CommentConsidering all factors, such as the temporal relationship between the seizure onset and quetiapine intake, the exclusion of other possible etiology of seizures and their cessation after drug withdrawal, we judged that quetiapine precipitated seizure activity in both patients. These cases serve as a reminder that postmarketing surveillance of newly released medications, clinical awareness of seizure potential when using these medications, and the need for risk factor evaluation before starting psychotropic medications are essential.Department of Psychiatry, Kocaeli University, Kocaeli, TurkeyDepartment of Child and Adolescent Psychiatry, Kocaeli University, Kocaeli, TurkeyDepartment of Child and Adolescent Psychiatry, Istanbul University, Kocaeli, TurkeyReferences1 . Aman MG, Lindsay RL, Nash PL, et al: Individuals with mental retardation, in Pediatric Psychopharmacology Principles and Practice. Edited by Martin A, Scahill L, Charney DS, et al. New York, Oxford University Press, 2003, pp 617–630Google Scholar2 . Cummings MR, Miller BD: Pharmacologic management of behavioral instability in medically ill pediatric patients. Curr Opin Pediatr 2004; 16:516–522Google Scholar FiguresReferencesCited byDetailsCited ByZentrales NervensystemQuetiapine-induced absence seizures in a dementia patient19 October 2016 | Geriatrics & Gerontology International, Vol. 16, No. 10QuetiapineJournal of Affective Disorders, Vol. 138, No. 3 Volume 19Issue 3 Summer, 2007Pages 341-342 Metrics PDF download History Published online 1 July 2007 Published in print 1 July 2007

Treatment of Intractable Hiccups With Olanzapine Following Recent Severe Traumatic Brain Injury

Treatment of Intractable Hiccups With Olanzapine Following Recent Severe Traumatic Brain Injury

Persistent Amnesia as a Sequel of Olanzapine-Induced Neuroleptic Malignant Syndrome

Back to table of contents Previous article Next article LETTERFull AccessPersistent Amnesia as a Sequel of Olanzapine-Induced Neuroleptic Malignant SyndromeD.N. Mendhekar, M.D., D.P.M.,Harpreet S. Duggal, M.D., D.P.M.,D.N. Mendhekar, M.D., D.P.M.Search for more papers by this author,Harpreet S. Duggal, M.D., D.P.M.Search for more papers by this author,Published Online:1 Oct 2006AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR : Persistent long-term cognitive sequelae of neuroleptic malignant syndrome (NMS) appear to be rare. 1 Memory problems as sequelae of NMS have been anecdotally reported with NMS associated with typical antipsychotics, but to our knowledge, there are no reports associating it with NMS due to atypical antipsychotics. 2 , 3 A case of persistent amnesia is described in a patient who developed NMS with olanzapine. Case Report “Mr. A,” a 16-year-old adolescent, with a history of schizophreniform disorder of 6 week’s duration, was initially treated with haloperidol (10 mg/day). However, this was discontinued within a week due to severe extrapyramidal symptoms (EPS). Mr. A did not receive any medication for the next 2 weeks and was then started on a regimen of olanzapine, 7.5 mg/day. A week later, he developed severe EPS again and olanzapine was stopped and the patient was treated with trihexyphenidyl (4 mg/day) and lorazepam (1 mg/day). Three days later, Mr. A developed a fever and worsening EPS. Over the next 3 days, this evolved into a full-blown NMS characterized by a fever of 102°F, marked rigidity, altered sensorium, urinary incontinence, labile blood pressure, tachycardia, and excessive sweating. Serum creatine phosphokinase (CPK) was 1,144 IU/liter (normal range, 0–200) and WBC count was 15 x10 9 (normal range, 4.5–11.0). Other blood work, including renal, hepatic, and electrolyte profiles were normal. He scored 5/30 on the Mini-Mental State Examination (MMSE). His computed tomography head scan did not reveal any acute changes. He was subsequently treated with norfloxacin for a urinary tract infection. Four days after Mr. A developed hyperpyrexia, he was treated with bromocriptine for the next 4 weeks. Ten days after starting treatment with bromocriptine, the patient no longer displayed any physical symptoms of NMS with the CPK and WBC count returning to normal. However, he continued to exhibit significant cognitive deficits and his MMSE score was only 14/30. He had intact attention, concentration, and calculation, but was only oriented to person and had impaired immediate and delayed recall. His mental status was remarkable for confabulation, perseveration, and echolalia. No fluctuation in consciousness or perceptual abnormalities suggestive of delirium were noted. His remote memory was relatively intact. On discharge, Mr. A continued to show improvement in his cognitive functions, and 2 months after the onset of NMS, his score on MMSE was 25/30 with persistent deficits in immediate and recent memory. He still had retrograde amnesia about the events surrounding the NMS and also had anterograde amnesia with deficits in learning new verbal information. Again, no deficits were noted in remote memory. Comment This patient met DSM-IV criteria for NMS. The cognitive deficits seen in this patient following NMS are reminiscent of an organic amnestic disorder, a rare entity described in patients recovering from NMS. 2 , 3 Of interest, among all the cognitive domains, memory impairment is the only one that has been consistently reported on recovery from NMS. Whether the concurrent urinary tract infection and the resultant delirium could have contributed to this presentation cannot be entirely ruled out. However, this seems less likely as this patient continued to exhibit cognitive deficits long after recovery from the urinary tract infection. Moreover, the Physicians’ Desk Reference does not suggest any association of norfloxacin with cognitive deficits. Some investigators have speculated that these persistent deficits may be a consequence of complications of NMS, such as prolonged hypoxia and extreme hyperthermia. 1 This is supported by reports of memory deficit as a neuropsychological sequela of heat stroke. 4 In conclusion, more research is encouraged to explore why memory is preferentially involved in NMS. Excitotoxicity due to glutamate surge has been implicated in ECT-induced memory dysfunction, 5 and glutamate has also been hypothesized to play a role in NMS. 6 Thus, it would be interesting to decipher the role of this neurotransmitter in long-term cognitive sequelae of NMS. Delhi, IndiaHerrick Memorial Hospital, Tecumseh, Mich

Reversible Neutropenia With Olanzapine Following Clozapine-Induced Neutropenia

Back to table of contents Previous article Next article Letters to the EditorFull AccessReversible Neutropenia With Olanzapine Following Clozapine-Induced NeutropeniaP. Thangadurai D.P.M.K.S. Jyothi D.P.M.Rajesh Gopalakrishnan D.P.M., M.D.Anju Kuruvilla M.D.K.S. Jacob M.D., PH.D., M.R.C.PSYCH.,P. Thangadurai D.P.M.Search for more papers by this authorK.S. Jyothi D.P.M.Search for more papers by this authorRajesh Gopalakrishnan D.P.M., M.D.Search for more papers by this authorAnju Kuruvilla M.D.Search for more papers by this authorK.S. Jacob M.D., PH.D., M.R.C.PSYCH.Search for more papers by this author,Published Online:1 Jul 2006https://doi.org/10.1176/ajp.2006.163.7.1298AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: A major limitation with clozapine is the risk of agranulocytosis, which is observed in 1% of patients taking clozapine. In addition, olanzapine has been found to produce reversible neutropenia (1 , 2) . There are reports of both safe usage and the prolongation of granulocytopenia when olanzapine is used after clozapine-induced agranulocytosis (3 , 4) . We report a case in which a patient who had no adverse hematological responses to olanzapine developed neutropenia when he was re-exposed to olanzapine following clozapine-induced neutropenia. A 31-year-old Asian man with schizophrenia remained well for two years. He had been taking 20 mg of olanzapine, with no positive symptoms and minimal negative symptoms. Six months after the dose was gradually reduced, he developed a relapse of psychotic symptoms. He received sequential trials of risperidone (8 mg), olanzapine (30 mg), and a course of electroconvulsive therapy (because of severe agitation and suicidal and homicidal risks). During this period, his total white blood cell count ranged from 8,300/mm 3 to 10,200/mm 3 . As he remained symptomatic, a trial of clozapine was considered. A preclozapine laboratory test was unremarkable. While there was a significant reduction in psychotic symptoms, the patient’s total white blood cell count dropped to 2,100/mm 3 , and he developed a chest infection in the fifth week of treatment. Clozapine was discontinued, and oral cephalosporins and quinolones were started. The patient’s physical condition improved, and his white blood cell count normalized to 7,900/mm 3 within 10 days. He was restarted on a regimen of olanzapine and remained hematologically stable during the subsequent 2 weeks, with white blood cell counts of 7,600/mm 3 and 7,900/mm 3 . However, during the third week after normal white blood cell counts, his cell count decreased again to 3,600/mm 3 and later to 3,200/mm 3 . Olanzapine was discontinued, and within a week the total white blood cell count rose to 10,100/mm 3 . Clinical history, physical examination, and laboratory tests did not show evidence of any other medical disorder. To date, there are no reports of neutropenia in patients who have been previously hematologically stable on olanzapine when re-exposed to it following clozapine-induced neutropenia or agranulocytosis. In addition, there is no literature on the mechanism of olanzapine-induced neutropenia, but in view of its structural similarity to clozapine, similar mechanisms may be responsible. Previous reports have suggested that olanzapine can be safely administered to patients who develop agranulocytosis while taking clozapine (3) . Our report cautions against such use and raises the possibility that exposure to clozapine could sensitize the immune system, making it susceptible to olanzapine-induced neutropenia. Our experience suggests that patients who develop clozapine-induced neutropenia should have their neutrophil count monitored regularly during treatment with olanzapine, even if they have not had any hematological adverse effects with olanzapine in the past. Vellore, Tamilnadu, India

Reversible Neutropenia With Olanzapine Following Clozapine-Induced Neutropenia

Back to table of contents Previous article Next article Letters to the EditorFull AccessReversible Neutropenia With Olanzapine Following Clozapine-Induced NeutropeniaP. Thangadurai D.P.M.K.S. Jyothi D.P.M.Rajesh Gopalakrishnan D.P.M., M.D.Anju Kuruvilla M.D.K.S. Jacob M.D., PH.D., M.R.C.PSYCH.,P. Thangadurai D.P.M.Search for more papers by this authorK.S. Jyothi D.P.M.Search for more papers by this authorRajesh Gopalakrishnan D.P.M., M.D.Search for more papers by this authorAnju Kuruvilla M.D.Search for more papers by this authorK.S. Jacob M.D., PH.D., M.R.C.PSYCH.Search for more papers by this author,Published Online:1 Jul 2006https://doi.org/10.1176/ajp.2006.163.7.1298AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: A major limitation with clozapine is the risk of agranulocytosis, which is observed in 1% of patients taking clozapine. In addition, olanzapine has been found to produce reversible neutropenia (1 , 2) . There are reports of both safe usage and the prolongation of granulocytopenia when olanzapine is used after clozapine-induced agranulocytosis (3 , 4) . We report a case in which a patient who had no adverse hematological responses to olanzapine developed neutropenia when he was re-exposed to olanzapine following clozapine-induced neutropenia. A 31-year-old Asian man with schizophrenia remained well for two years. He had been taking 20 mg of olanzapine, with no positive symptoms and minimal negative symptoms. Six months after the dose was gradually reduced, he developed a relapse of psychotic symptoms. He received sequential trials of risperidone (8 mg), olanzapine (30 mg), and a course of electroconvulsive therapy (because of severe agitation and suicidal and homicidal risks). During this period, his total white blood cell count ranged from 8,300/mm 3 to 10,200/mm 3 . As he remained symptomatic, a trial of clozapine was considered. A preclozapine laboratory test was unremarkable. While there was a significant reduction in psychotic symptoms, the patient’s total white blood cell count dropped to 2,100/mm 3 , and he developed a chest infection in the fifth week of treatment. Clozapine was discontinued, and oral cephalosporins and quinolones were started. The patient’s physical condition improved, and his white blood cell count normalized to 7,900/mm 3 within 10 days. He was restarted on a regimen of olanzapine and remained hematologically stable during the subsequent 2 weeks, with white blood cell counts of 7,600/mm 3 and 7,900/mm 3 . However, during the third week after normal white blood cell counts, his cell count decreased again to 3,600/mm 3 and later to 3,200/mm 3 . Olanzapine was discontinued, and within a week the total white blood cell count rose to 10,100/mm 3 . Clinical history, physical examination, and laboratory tests did not show evidence of any other medical disorder. To date, there are no reports of neutropenia in patients who have been previously hematologically stable on olanzapine when re-exposed to it following clozapine-induced neutropenia or agranulocytosis. In addition, there is no literature on the mechanism of olanzapine-induced neutropenia, but in view of its structural similarity to clozapine, similar mechanisms may be responsible. Previous reports have suggested that olanzapine can be safely administered to patients who develop agranulocytosis while taking clozapine (3) . Our report cautions against such use and raises the possibility that exposure to clozapine could sensitize the immune system, making it susceptible to olanzapine-induced neutropenia. Our experience suggests that patients who develop clozapine-induced neutropenia should have their neutrophil count monitored regularly during treatment with olanzapine, even if they have not had any hematological adverse effects with olanzapine in the past. Vellore, Tamilnadu, India

Chronic administration of olanzapine induces metabolic and food intake alterations: a mouse model of the atypical antipsychotic-associated adverse effects

Most of atypical antipsychotics (AAPs) are highly related to a major risk of metabolic drawbacks leading to dyslipidemia and obesity. To set up a mouse model of the AAP-associated weight gain in mice under the influence of chronic olanzapine regimen. Female mice were housed in pairs and habituated to spontaneous feeding with a high-palatable diet (10% sucrose wet mash). Firstly, we orally administered olanzapine (0.75, 1.5 and 3 mg/kg), evaluating body weight and periuterine fat mass, as well as insulin, non-esterified fatty acids, triglycerides, and glucose levels. In a second experiment, we assessed the effect of olanzapine on energy expenditure through indirect calorimetry (IC). A third experiment was conducted to investigate the effects of olanzapine on a high fat-high sweet palatable diet (10% sucrose + 30% fat, HF-HS) in mice implanted with subcutaneous osmotic mini-pumps. Locomotor activity was also assessed. In experiment 1, the highest dose of chronically administered olanzapine (3 mg/kg) induced significant weight gain accompanied by augmentation of periuterine fat depots, with no changes in locomotor activity. In experiment 2, chronic administration did not alter energy expenditure, whereas, decreased respiratory quotient (RQ). In experiment 3, subcutaneously infused olanzapine evidenced a dose and time-dependent increase of body weight and HF-HS diet consumed. Notably, serum analyses revealed a hyperinsulinemia together with increased levels of triglycerides and glucose. In this study, we describe in female mice metabolic alterations matching the metabolic syndrome, thus resembling the clinical situation of schizophrenic patients taking AAPs.

Effect of Olanzapine on Body Composition and Energy Expenditure in Adults With First-Episode Psychosis

Weight gain is a commonly observed adverse effect of atypical antipsychotic medications, but associated changes in energy balance and body composition are not well defined. The authors report here the effect of olanzapine on body weight, body composition, resting energy expenditure, and substrate oxidation as well as leptin, insulin, glucose, and lipid levels in a group of outpatient volunteers with first-episode psychosis. Nine adults (six men and three women) experiencing their first psychotic episode who had no previous history of antipsychotic drug therapy began a regimen of olanzapine and were studied within 7 weeks and approximately 12 weeks after olanzapine initiation. After approximately 12 weeks of olanzapine therapy, the median increase in body weight was 4.7 kg, a significant increase of 7.3% from first observation. Body fat, measured by dual-energy x-ray absorptiometry, increased significantly, with a propensity for central fat deposition. Lean body mass and bone mineral content did not change. Resting energy expenditure, measured by indirect calorimetry, did not change. Respiratory quotient significantly increased 0.12 with olanzapine and was greatest in those who gained >5% of their initial weight. Fasting insulin, C-peptide, and triglyceride levels significantly increased, but there were no changes in glucose levels; total, high density lipoprotein, or low density lipoprotein cholesterol levels; or leptin levels. Olanzapine appears to have induced an increase in central body fat deposition, insulin, and triglyceride levels, suggesting the possible development of insulin resistance. The decrease in fat oxidation may be secondary or predispose patients to olanzapine-induced weight gain.