olanzapine and Hypotension

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure <90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Arrhythmias, Cardiac; Coronary Care Units; Delirium; Endocarditis; Female; Heart Arrest; Heart Failure; Humans; Hypotension; Length of Stay; Long QT Syndrome; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Shock, Cardiogenic; ST Elevation Myocardial Infarction; Tachycardia, Ventricular

BACKGROUND Olanzapine is an antipsychotic drug and is used in critical care to treat delirium. There is no known antidote to olanzapine intoxication. Overdosing olanzapine can cause, tremor, bradykinesia, hypotension somnolence, coma, and miosis. CASE REPORT We present the case of a previously healthy 69-year-old man who after routine mitral valve surgery developed pneumonia and severe sepsis requiring several weeks on a ventilator in the Intensive Care Unit. He developed delirium and paranoia and was prescribed olanzapine. After 4 doses, he became hypotensive and nonresponsive and developed pinpoint pupils. The symptoms were reversed minutes after administration of flumazenil. The clinical picture in this case corresponds well with an olanzapine intoxication. No other drugs, such as benzodiazepines or opioids, had been administered that could explain the reaction. Olanzapine intoxication is known to present with hypotension, coma, and miosis. The doses given were normal starting doses for olanzapine in the outpatient setting but much higher than recommended doses in the intensive care setting. CONCLUSIONS This case illustrates a risk for severe adverse effects, even within normal prescription range, when olanzapine is used in the intensive care setting. Finally, it is intriguing that the symptoms were reversed after administration of flumazenil, a selective competitive antagonist of the GABA receptor. Olanzapine mainly effects dopamine, serotonin, a1-adrenergic, histamine, and muscarinic receptors, but a low affinity to GABA and benzodiazepine sites can perhaps explain the observed effect.

Topics: Aged; Benzodiazepines; Coma; Delirium; Flumazenil; Humans; Hypotension; Intensive Care Units; Male; Miosis; Olanzapine

Several adverse outcomes attributed to atypical antipsychotic drugs, specifically quetiapine, risperidone, and olanzapine, are known to cause acute kidney injury (AKI). Such outcomes include hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis.. To investigate the risk for AKI and other adverse outcomes associated with use of atypical antipsychotic drugs versus nonuse.. Population-based cohort study.. Ontario, Canada, from 2003 to 2012.. Adults aged 65 years or older who received a new outpatient prescription for an oral atypical antipsychotic drug (n=97,777) matched 1:1 with those who did not receive such a prescription.. The primary outcome was hospitalization with AKI (assessed by using a hospital diagnosis code and, in a subpopulation, serum creatinine levels) within 90 days of prescription for atypical antipsychotic drugs.. Atypical antipsychotic drug use versus nonuse was associated with a higher risk for hospitalization with AKI (relative risk [RR], 1.73 [95% CI, 1.55 to 1.92]). This association was consistent when AKI was assessed in a subpopulation for which information on serum creatinine levels was available (5.46% vs. 3.34%; RR, 1.70 [CI, 1.22 to 2.38]; absolute risk increase, 2.12% [CI, 0.80% to 3.43%]). Drug use was also associated with hypotension (RR, 1.91 [CI, 1.60 to 2.28]), acute urinary retention (RR, 1.98 [CI, 1.63 to 2.40]), and all-cause mortality (RR, 2.39 [CI, 2.28 to 2.50]).. Only older adults were included in the study.. Atypical antipsychotic drug use is associated with an increased risk for AKI and other adverse outcomes that may explain the observed association with AKI. The findings support current safety concerns about the use of these drugs in older adults.. Academic Medical Organization of Southwestern Ontario.

Topics: Acute Kidney Injury; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cause of Death; Creatinine; Dibenzothiazepines; Female; Hospitalization; Humans; Hypotension; Male; Olanzapine; Ontario; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Urinary Retention

This is a case of a citalopram and olanzapine overdose causing seizures and severe cardiotoxicity.. A 21-year-old man presented unresponsive, with seizures, to an Emergency Department. The patient's initial electrocardiogram demonstrated a widened QRS of 160 ms and a normal QT/QTc interval of 400/487 ms consistent with cardiac sodium channel blockade. Within 30 min of arrival, peak citalopram and olanzapine levels were measured to be 522 ng/mL and 505 ng/mL, respectively. Measured levels remained supratherapeutic until 13.6 h and 42.6 h after arrival for citalopram and olanzapine, respectively. The patient developed bradycardia and hypotension that required multimodal therapies including sodium bicarbonate boluses, vasopressors, and transvenous pacing. Seizures and cardiotoxicity continued while citalopram, but not olanzapine, was supratherapeutic.. This case describes cardiotoxicity directly correlated with supratherapeutic citalopram levels in overdose.

Topics: Adult; Benzodiazepines; Bradycardia; Citalopram; Drug Overdose; Electrocardiography; Humans; Hypotension; Male; Olanzapine; Seizures; Selective Serotonin Reuptake Inhibitors; Young Adult

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Fatal Outcome; Female; Humans; Hypotension; Male; Middle Aged; Olanzapine; Pulmonary Embolism; Schizophrenia, Paranoid

Delirium is a transient global disorder of cognition. Almost any medical illness or medication can cause delirium. Here, we report a 71-year-old male who presented to the emergency department with a sudden change in mental status, which later resolved. An electrocardiogram was consistent with acute myocardial infarction. The patient later developed symptoms of delirium, and haloperidol was administered. The symptoms did not resolve, and risperidone was initiated instead. The patient subsequently became hypotensive, and treatment was again changed to olanzapine. He returned to full consciousness with olanzapine treatment. When the potential hypotensive effects of haloperidol and risperidone are taken into consideration, in patients with high cardiac risk, olanzapine may provide a better option for the treatment of delirium.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Delirium; Humans; Hypotension; Male; Myocardial Infarction; Olanzapine; Risperidone

Topics: Antipsychotic Agents; Benzodiazepines; Drug Approval; Drug Interactions; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Hypotension; Injections, Intramuscular; Lorazepam; Male; Middle Aged; Olanzapine; Schizophrenia, Paranoid; United States

Olanzapine, an atypical antipsychotic, is often regarded as a safe choice for psychosis management. We hereby report an aged case that presented with conscious depression, bradycardia, hypotension, miosis and hypothermia. Olanzapine was thought to be the offending agent. His condition improved with supportive therapy.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bradycardia; Cardiovascular Diseases; Delusions; Dementia; Humans; Hypotension; Hypothermia; Male; Olanzapine

Olanzapine is an atypical antipsychotic medication indicated for the treatment of schizophrenia and other manifestations of psychotic illness. Common side effects include somnolence, constipation, weight gain, and postural hypotension. The authors report a case of hypotension accompanied by bradycardia in a normal, healthy volunteer participating in an olanzapine pharmacokinetic study following a single 5 mg dose. A venous catheter allowed for serial blood sampling of olanzapine concentrations before, during, and after the adverse event. The subject experienced a rapid absorption of the drug and higher than anticipated maximum plasma concentrations. This case suggests that atypical antipsychotics, although generally better tolerated than conventional agents, may still result in untoward reactions that may be partially due to individual differences in drug absorption and metabolism.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Pressure; Bradycardia; Double-Blind Method; Female; Heart Rate; Humans; Hypotension; Olanzapine; Pirenzepine