olanzapine and Delirium

Delirium is likely present in the neonatal intensive care unit and has been largely unrecognized. There are several risk factors for delirium including illness severity, neurosedative exposure, and environmental disruptions that put infants at risk for delirium. Regular use of scoring systems should be considered to improve delirium detection. When identified, initial steps in management should include resolving underlying causes and implementation of standard nonpharmacologic measures. Mounting pediatric evidence suggests that the atypical antipsychotics, as well as the α-2 agonists, may be additionally beneficial in treating delirium as well as improving the ability to wean off other neurosedative medications.

Topics: Antipsychotic Agents; Benzodiazepines; Child; Delirium; Humans; Infant; Infant, Newborn; Olanzapine; Risperidone

Olanzapine is an effective antipsychotic drug used in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders. It belongs to the 2nd generation antipsychotics, its mechanism of action ranks among multireceptor antagonists (MARTA); it affects the dopamine, serotonin, adrenaline, histamine, and muscarinic systems. The broad pharmacodynamic profile of olanzapine provides for a broad indication spectrum with a better adverse effect profile compared to conventional antipsychotics. It can be used in a number of situations to benefit cancer patients in palliative care as well as in the terminal stages of the disease.. The review article presents possible indications for olanzapine in oncological palliative care. Apart from dealing with delirium and anxiety, indications for the use of antipsychotics in palliative medicine include the management of nausea, vomiting and loss of appetite. Olanzapine is an effective antiemetic in cancer patients with tumor-induced nausea and in antiemetic regimens for chemotherapy-induced nausea and vomiting. Olanzapine is an effective treatment for delirium, as effective as haloperidol, but with a lower toxicity profile. It increases appetite and can be used with advantage in patients with anorexia and weight loss. It is possible to use its anxiolytic and mood-stabilizing effects; in many situations, it can serve well as a co-analgesic, especially in the so-called total pain. It is proven to increase the quality of life of patients with advanced cancer.. Due to its effect, simple dosage and a good safety profile, olanzapine is a useful drug for the routine clinical practice of an oncologist - a non-psychiatrist.

Topics: Antiemetics; Antipsychotic Agents; Delirium; Humans; Nausea; Neoplasms; Olanzapine; Palliative Care; Quality of Life; Vomiting

Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain distressing or dangerous, or both. It is unclear how well these recommendations are supported by current evidence.. Our primary objective was to assess the efficacy of antipsychotics versus nonantipsychotics or placebo on the duration of delirium in hospitalised adults. Our secondary objectives were to compare the efficacy of: 1) antipsychotics versus nonantipsychotics or placebo on delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects; and 2) atypical vs. typical antipsychotics for reducing delirium duration, severity, and resolution, hospital mortality and length of stay, discharge disposition, health-related quality of life, and adverse effects.. We searched MEDLINE, Embase, Cochrane EBM Reviews, CINAHL, Thomson Reuters Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) from their respective inception dates until July 2017. We also searched the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database, Web of Science ISI Proceedings, and other grey literature.. We included randomised and quasi-randomised trials comparing 1) antipsychotics to nonantipsychotics or placebo and 2) typical to atypical antipsychotics for the treatment of delirium in adult hospitalised (but not critically ill) patients.. We examined titles and abstracts of identified studies to determine eligibility. We extracted data independently in duplicate. Disagreements were settled by further discussion and consensus. We used risk ratios (RR) with 95% confidence intervals (CI) as a measure of treatment effect for dichotomous outcomes, and between-group standardised mean differences (SMD) with 95% CI for continuous outcomes.. We included nine trials that recruited 727 participants. Four of the nine trials included a comparison of an antipsychotic to a nonantipsychotic drug or placebo and seven included a comparison of a typical to an atypical antipsychotic. The study populations included hospitalised medical, surgical, and palliative patients.No trial reported on duration of delirium. Antipsychotic treatment did not reduce delirium severity compared to nonantipsychotic drugs (standard mean difference (SMD) -1.08, 95% CI -2.55 to 0.39; four studies; 494 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (SMD -0.17, 95% CI -0.37 to 0.02; seven studies; 542 participants; low-quality evidence). There was no evidence antipsychotics resolved delirium symptoms compared to nonantipsychotic drug regimens (RR 0.95, 95% CI 0.30 to 2.98; three studies; 247 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (RR 1.10, 95% CI 0.79 to 1.52; five studies; 349 participants; low-quality evidence). The pooled results indicated that antipsychotics did not alter mortality compared to nonantipsychotic regimens (RR 1.29, 95% CI 0.73 to 2.27; three studies; 319 participants; low-quality evidence) nor was there a difference between typical and atypical antipsychotics (RR 1.71, 95% CI 0.82 to 3.35; four studies; 342 participants; low-quality evidence).No trial reported on hospital length of stay, hospital discharge disposition, or health-related quality of life. Adverse event reporting was limited and measured with inconsistent methods; in those reporting events, the number of events were low. No trial reported on physical restraint use, long-term cognitive outcomes, cerebrovascular events, or QTc prolongation (i.e. increased time in the heart's electrical cycle). Only one trial reported on arrhythmias and seizures, with no difference between typical or atypical antipsychotics. We found antipsychotics did not have a higher risk of extrapyramidal symptoms (EPS) compared to nonantipsychotic drugs (RR 1.70, 95% CI 0.04 to 65.57; three studies; 247 participants; very-low quality evidence); pooled results showed no increased risk of EPS with typical antipsychotics compared to atypical antipsychotics (RR 12.16, 95% CI 0.55 to 269.52; two studies; 198 participants; very low-quality evidence).. There were no reported data to determine whether antipsychotics altered the duration of delirium, length of hospital stay, discharge disposition, or health-related quality of life as studies did not report on these outcomes. From the poor quality data available, we found antipsychotics did not reduce delirium severity, resolve symptoms, or alter mortality. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms were not more frequent with antipsychotics compared to nonantipsychotic drug regimens, and no different for typical compared to atypical antipsychotics.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Female; Haloperidol; Hospitalization; Humans; Male; Olanzapine; Placebo Effect; Randomized Controlled Trials as Topic; Risperidone

Consensus panel guidelines advocate for the judicious use of antipsychotic drugs to manage delirium in hospitalized patients when nonpharmacologic measures fail and the patient is in significant distress from symptoms, poses a safety risk to self or others, or is impeding essential aspects of his or her medical care. Here, we review the use of haloperidol, olanzapine, quetiapine, risperidone, and aripiprazole for this purpose.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Delirium; Haloperidol; Hospitalization; Humans; Olanzapine; Quetiapine Fumarate; Risperidone

Second-generation antipsychotics (SGAs) are a mainstay in the treatment of patients with schizophrenia. However, continuity in intake of the prescribed medication has been one of the greatest challenges in these patients. One option to improve medication adherence is to prescribe depot or long-acting injectable formulations (LAIs) of antipsychotics. Following risperidone, several other SGAs have been introduced as LAIs. Olanzapine pamoate, paliperidone palmitate, and aripiprazole are the new-generation LAIs, which are available for 2- to 4-week intervals of application in many countries. The literature shows a clear advantage of these drugs over placebo regarding symptom reduction and relapse prevention. LAIs show a similar safety profile to oral formulations of the relevant drug, with the exception of olanzapine pamoate, which can lead to rare cases of post-injection delirium/sedation syndrome (PDSS). PDSS is characterized by heavy sedation (possibly including coma) and/or delirium after injection. During PDSS events, patients show higher plasma concentrations of olanzapine, leading to the assumption that unintended partial intravascular injection or blood vessel injury during the injection is causative of PDSS. Therefore, a risk-management plan proposing an observation period of 3 h was introduced. In August 2013, a new proposal by the European Medicines Agency terminated the requirement to accompany these patients to their next destination, although this requirement remains in place according to US FDA recommendations.

Topics: Antipsychotic Agents; Benzodiazepines; Deep Sedation; Delayed-Action Preparations; Delirium; Humans; Olanzapine

Delirium is a complex but common disorder in palliative care with a prevalence between 13 and 88 % but a particular frequency at the end of life (terminal delirium). By reviewing the most relevant studies (MEDLINE, EMBASE, PsycLit, PsycInfo, Cochrane Library), a correct assessment to make the diagnosis (e.g., DSM-5, delirium assessment tools), the identification of the possible etiological factors, and the application of multicomponent and integrated interventions were reported as the correct steps to effectively manage delirium in palliative care. In terms of medications, both conventional (e.g., haloperidol) and atypical antipsychotics (e.g., olanzapine, risperidone, quetiapine, aripiprazole) were shown to be equally effective in the treatment of delirium. No recommendation was possible in palliative care regarding the use of other drugs (e.g., α-2 receptors agonists, psychostimulants, cholinesterase inhibitors, melatonergic drugs). Non-pharmacological interventions (e.g., behavioral and educational) were also shown to be important in the management of delirium. More research is necessary to clarify how to more thoroughly manage delirium in palliative care.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cholinesterase Inhibitors; Delirium; Disease Management; Haloperidol; Health Personnel; Humans; Olanzapine; Palliative Care; Quetiapine Fumarate; Risperidone

Topics: Adolescent; Animals; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antipsychotic Agents; Autoantibodies; Benzodiazepines; Cerebrospinal Fluid; Delirium; Female; Humans; Length of Stay; Olanzapine; Patient Transfer; Receptors, N-Methyl-D-Aspartate

Delirium is a serious and common problem in severely medically ill patients of all ages. It has been less addressed in children and adolescents. Treatment of delirium is predicated on addressing its underlying cause. The management of its symptoms depends on the off-label use of antipsychotics, while avoiding agents that precipitate or worsen delirium. Olanzapine, quetiapine, and risperidone are presently considered first-line drugs, usually replacing haloperidol. Other agents have shown promise, including melatonin to address the sleep disturbance characteristic of delirium, and dexmedetomidine, an α2-agonist, that may facilitate lower doses of benzodiazepines and opioids that may worsen delirium.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Delirium; Dexmedetomidine; Dibenzothiazepines; Humans; Melatonin; Olanzapine; Quetiapine Fumarate; Risperidone

Traditionally, haloperidol has been the recommended antipsychotic drug for pharmacological treatment of delirium, which is a frequent complication in the critical care setting. Due to a less frequent occurrence of extrapyramidal adverse effects, second-generation antipsychotic drugs have been evaluated. In the present paper we review the current randomized prospective studies of second-generation antipsychotics as treatment for delirium in hospitalized patients and conclude that so far the evidence in favour of these drugs compared with haloperidol is still sparse.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Delirium; Evidence-Based Medicine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Sulpiride; Thiazoles

Traditionally, haloperidol has been the recommended antipsychotic drug for pharmacological treatment of delirium, which is a frequent complication in the critical care setting. Due to a less frequent occurrence of extrapyramidal adverse effects, second-generation antipsychotic drugs have been evaluated. In the present paper we review the current randomized prospective studies of second-generation antipsychotics as treatment for delirium in hospitalized patients and conclude that so far the evidence in favour of these drugs compared with haloperidol is still sparse.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Delirium; Evidence-Based Medicine; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Sulpiride; Thiazoles

This systematic literature review aims to collect and analyse relevant clinical trials for the drug treatment of delirium in palliative care. The search was conducted including July 2012 in Medline (from 1966) and Embase (from 1974). The search retrieved 448 studies, of which 3 studies could be included in the analysis. Treatment with the antipsychotic drug haloperidol can be recommended, which is also true to a somewhat lower extent for the antipsychotics olanzapine and aripiprazole. Treatment with lorazepam only should be avoided. This literature analysis reflects the positive clinical experience, especially when using haloperidol. To confirm these recommendations, further substantial clinical studies are needed.The English full-text version of this article can be found at SpringerLink (under "Supplemental").

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clinical Trials as Topic; Delirium; Evidence-Based Medicine; Haloperidol; Humans; Hypnotics and Sedatives; Lorazepam; Olanzapine; Palliative Care; Piperazines; Quinolones; Risk Factors

The aim of this study was to review the efficacy and safety of atypical antipsychotics, comparing within class, placebo, or compared to another active treatment for delirium. A literature search was conducted using PubMed, EMBASE, and the Cochrane database (1 January 1990-5 November 2012). Selection criteria for review were prospective, controlled studies (comparison studies), using validated delirium rating scales as outcome measures. A total of six prospective, randomized controlled studies were included in the review. It was found that atypical antipsychotics are effective and safe in treating delirium, even though there seemed to be no difference between each agent. In particular, comparison studies with haloperidol showed that the efficacy of atypical antipsychotics was similar to that of low-dose haloperidol. It was concluded that atypical antipsychotics appear to be effective and tolerable in the management of delirium, even though the evidence is limited.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Delirium; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Sulpiride; Thiazoles

An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI). During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI.. Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors.. Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness). However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified.. Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post-injection observation period.. ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Cognition Disorders; Delayed-Action Preparations; Delirium; Drug Administration Schedule; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Incidence; Injections, Intramuscular; Olanzapine; Risk Factors; Schizophrenia; Sleep; Syndrome; Treatment Outcome

The past few years have witnessed increased research into delirium treatment and related issues, leading to better management (e.g. improved detection) and better understanding of phenomenology and pathophysiology. Many treatment and prevention trials have been conducted.. Delirium phenomenology studies revealed that even subsyndromal presentations may bear a poor prognosis. Varied pathophysiology may lead to different delirium subtypes with implications for treatment, especially the hypoactive subtype, for which systematic neuroleptic treatment remains controversial. The high prevalence of delirium has led to improved use of validated instruments and better trials. Nonpharmacological interventions remain an essential step in delirium management and have yielded positive results, especially in prevention. Two trials of haloperidol prophylaxis identified reduced severity and duration of delirium in one and reduced incidence in the other. Trials comparing haloperidol with atypical antipsychotics, mainly risperidone and olanzapine, found equal efficacy but more side effects with haloperidol.. Use of validated detection instruments is now standard procedure in both specialized clinical practice and research. Although haloperidol remains the mainstay of treatment, recent trials have begun to discriminate between the use of different agents and pharmacological approaches.

Topics: Antipsychotic Agents; Benzodiazepines; Delirium; Dopamine Antagonists; Haloperidol; Humans; Olanzapine; Palliative Care; Prognosis; Risperidone; Serotonin Antagonists; Severity of Illness Index; Time Factors

Delirium occurs frequently in hospitalized patients and is reported to occur at a rate of 10% to 40% in hospitalized elderly patients. The gold standard of treatment is to treat the underlying cause of delirium and use high-potency antipsychotics such as haloperidol to target the behavioral disturbances. Since the development of atypical antipsychotics, many psychiatric conditions that were previously only treatable using high-potency antipsychotics may now be managed with the atypical agents. This review will examine the current literature on atypical antipsychotics and summarize the results from published trials in order to evaluate the efficacy and potential benefits of atypical antipsychotics for the treatment of delirium in the elderly population.. A search of the published literature was conducted using MEDLINE and PubMed. The PubMed search was limited to articles that were (1) written in the English language, (2) focused on human subjects above age 65, and (3) were in the format of review articles, randomized controlled trials (RCTs), clinical trials, or meta-analyses. The initial PubMed search was conducted in March 2006 with follow-up investigations in April 2006 and July 2007.. Risperidone, the most thoroughly studied atypical antipsychotic, was found to be approximately 80% to 85% effective in treating the behavioral disturbances of delirium at a dosage of 0.5 to 4 mg daily. Studies of olanzapine indicated that it was approximately 70% to 76% effective in treating delirium at doses of 2.5 to 11.6 mg daily. Very few studies have been conducted using quetiapine; it also appears to be a safe and effective alternative to high-potency antipsychotics. In comparison to haloperidol, the frequency of adverse reactions and side effects was found to be much lower with the use of atypical antipsychotic medications. In the limited number of trials comparing atypical antipsychotics to haloperidol, haloperidol consistently produced a higher rate (an additional 10% to 13%) of extrapyramidal side effects.. A review of current literature supports the conclusion that atypical antipsychotic medications demonstrate similar rates of efficacy as haloperidol for the treatment of delirium in the elderly patient, with a lower rate of extrapyramidal side effects. There is limited evidence of true efficacy, since no double-blind placebo trials exist.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Delirium; Geriatrics; Haloperidol; Humans; Olanzapine; Risk Factors; Risperidone

With understanding of diagnostic criteria as well as predisposing and precipitating factors, clinicians can impact the morbidity and mortality of delirium.

Topics: Antioxidants; Antipsychotic Agents; Benzodiazepines; Delirium; Haloperidol; Hospitalization; Humans; Incidence; Melatonin; Olanzapine; Risk Factors

Delirium occurs in up to 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. Recently published reports have suggested that the standard drug for delirium, haloperidol, a typical antipsychotic that may cause adverse extrapyramidal symptoms among patients, may be replaced by atypical antipsychotics such as risperidone, olanzapine or quetiapine, that are as effective as haloperidol in controlling delirium, but that have a lower incidence of extrapyramidal adverse effects.. To compare the efficacy and incidence of adverse effects of haloperidol with risperidone, olanzapine, and quetiapine in the treatment of delirium.. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 August 2006 using the search terms:haloperidol or haldol or risperidone or risperdal* or quetiapine or seroquel* or olanzapine or zyprexa* or aminotriazole or sertindole or leponex* or zeldox* or ziprasidone.. Types of studies included unconfounded, randomised trials with concealed allocation of subjects. For inclusion trials had to have assessed patients pre- and post-treatment. Where cross-over studies are included, only data from the first part of the study were examined. Interrupted time series were excluded. Length of trial and number of measurements did not influence the selection of trials for study. Where indicated, individual patient data were requested for further examination.. Two reviewers extracted data from included trials. Data were pooled where possible, and analysed using appropriate statistical methods. Odds ratios of average differences were calculated. Only 'intention to treat' data were included. Analysis included haloperidol treated patients, compared with placebo.. Three studies were found that satisfied selection criteria. These studies compared haloperidol with risperidone, olanzapine, and placebo in the management of delirium and in the incidence of adverse drug reactions. Decrease in delirium scores were not significantly different comparing the effect of low dose haloperidol (< 3.0 mg per day) with the atypical antipsychotics olanzapine and risperidone (Odds ratio 0.63 (95% CI 10.29 - 1.38; p = 0.25). Low dose haloperidol did not have a higher incidence of adverse effects than the atypical antipsychotics. High dose haloperidol (> 4.5 mg per day) in one study was associated with an increased incidence of extrapyramidal adverse effects, compared with olanzapine. Low dose haloperidol decreased the severity and duration of delirium in post-operative patients, although not the incidence of delirium, compared to placebo controls in one study. There were no controlled trials comparing quetiapine with haloperidol.. There is no evidence that haloperidol in low dosage has different efficacy in comparison with the atypical antipsychotics olanzapine and risperidone in the management of delirium or has a greater frequency of adverse drug effects than these drugs. High dose haloperidol was associated with a greater incidence of side effects, mainly parkinsonism, than the atypical antipsychotics. Low dose haloperidol may be effective in decreasing the degree and duration of delirium in post-operative patients, compared with placebo. These conclusions must be tempered by the observation that they are based on small studies of limited scope, and therefore will require further corroborating evidence before they can be translated into specific recommendation for the treatment of delirium.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Female; Haloperidol; Humans; Male; Olanzapine; Randomized Controlled Trials as Topic; Risperidone

To review the existing literature of atypical antipsychotics in the treatment of delirium and make recommendations regarding their use in the treatment of delirium.. I conducted a literature search in Pubmed, Psychlit, and Embase for studies using atypical antipsychotics in the treatment of delirium. In the absence of studies, case reports were used.. Overall 13 studies examined the use of risperidone, olanzapine, and quetiapine, two cases were reported about ziprasidone, and no publication was found using aripiprazole in the treatment of delirium. Among the existing studies were retrospective and prospective, open label studies in addition to one with a double blind design using risperidone. Risperidone, olanzapine, and quetiapine may be all similarly effective in the treatment of delirium, whereas there may be limited efficacy in the use of olanzapine in the hypoactive subtype of delirium in elderly populations, which may generalize to the other atypical antipsychotics. The use of atypical antipsychotics in the treatment of delirium is safe and carries a low burden of side effects.. Although atypical antipsychotics are widely used in the treatment of delirium, well-designed studies do not exist. Among the existing studies, stronger data supports the use of risperidone and olanzapine, and also quetiapine may be considered in the treatment of delirium. Recommendations are made based on the existing data and literature. The need for well-designed studies to validate the use of atypical antipsychotics in the treatment of delirium continues.

Topics: Antipsychotic Agents; Benzodiazepines; Delirium; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome

The phenomenon of restlessness, agitation, or cognitive disturbances experienced by dying patients is well-known in palliative care; more than half of these patients will experience delirium symptoms at end-of-life. When not identified early and effectively managed, delirium symptoms could lead to caregiver and patient distress and harm.. Eighty patients with a prognosis of 7 days or less will be recruited for an open-label randomised control trial. The two arms compare oral-transmucosal haloperidol 2.5 mg vs olanzapine 5 mg over 72 h. The severity of agitation, delirium and toxicities of treatments will be compared at the 24th, 48th and 72nd hour after drug administration.. This trial is the first to compare anti-psychotics in the management of delirium at the dying stage in the home hospice setting using the oral transmucosal route. Ethical considerations, as well as recruitment procedures, are discussed.. This study was registered in ClinicalTrials.gov - identifier NCT04750395.

Topics: Antipsychotic Agents; Delirium; Haloperidol; Humans; Olanzapine; Psychomotor Agitation

Treatment of delirium often includes haloperidol. Second-generation antipsychotics like olanzapine have emerged as an alternative with possibly fewer side effects. The aim of this multicenter, phase III, randomized clinical trial was to compare the efficacy and tolerability of olanzapine with haloperidol for the treatment of delirium in hospitalized patients with advanced cancer.. Eligible adult patients (≥18 years) with advanced cancer and delirium (Delirium Rating Scale-Revised-98 [DRS-R-98] total score ≥17.75) were randomized 1:1 to receive either haloperidol or olanzapine (age-adjusted, titratable doses). Primary endpoint was delirium response rate (DRR), defined as number of patients with DRS-R-98 severity score <15.25 and ≥4.5 points reduction. Secondary endpoints included time to response (TTR), tolerability, and delirium-related distress.. Between January 2011 and June 2016, 98 patients were included in the intention-to-treat analysis. DRR was 45% (95% confidence interval [CI], 31-59) for olanzapine and 57% (95% CI, 43-71) for haloperidol (Δ DRR -12%; odds ratio [OR], 0.61; 95% CI, 0.2-1.4; p = .23). Mean TTR was 4.5 days (95% CI, 3.2-5.9 days) for olanzapine and 2.8 days (95% CI, 1.9-3.7 days; p = .18) for haloperidol. Grade ≥3 treatment-related adverse events occurred in 5 patients (10.2%) and 10 patients (20.4%) in the olanzapine and haloperidol arm, respectively. Distress rates were similar in both groups. The study was terminated early because of futility.. Delirium treatment with olanzapine in hospitalized patients with advanced cancer did not result in improvement of DRR or TTR compared with haloperidol. Clinical trial identification number. NCT01539733. Dutch Trial Register. NTR2559.. Guidelines recommend that pharmacological interventions for delirium treatment in adults with cancer should be limited to patients who have distressing delirium symptoms. It was suggested that atypical antipsychotics, such as olanzapine, outperform haloperidol in efficacy and safety. However, collective data comparing the efficacy and safety of typical versus atypical antipsychotics in patients with cancer are limited. If targeted and judicious use of antipsychotics is considered for the treatment of delirium in patients with advanced cancer, this study demonstrated that there was no statistically significant difference in response to haloperidol or olanzapine. Olanzapine showed an overall better safety profile compared with haloperidol, although this difference was not statistically significant.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Haloperidol; Humans; Neoplasms; Olanzapine; Risperidone

The objective of this study was to assess the long-term safety and efficacy of olanzapine long-acting injection (LAI). A 6-year, single-arm, open-label extension study of olanzapine LAI was conducted at 127 sites in 25 countries. Patients were 18-76 years of age, were diagnosed with schizophrenia or schizoaffective disorder (N=931), and had been previously enrolled in one of three clinical trials of olanzapine LAI. Patients received flexibly dosed (45-405 mg) olanzapine LAI every 2-4 weeks. The mean duration of exposure was ∼3 years. A total of 393 (42.2%) patients completed the study. The mean weight change was +2.1 kg (P<0.001), with 40.6% of patients experiencing 7% or higher weight gain. Treatment-emergent categorical changes occurred in fasting glucose, total cholesterol, and triglyceride levels. Pharmacokinetic analyses revealed no systemic accumulation of olanzapine after long-term treatment. There were 36 occurrences of post-injection delirium/sedation syndrome, all resolving within 72 h. The mean Positive and Negative Syndrome Scale total and subscale scores did not change significantly over the course of the study, indicating clinical stability. Olanzapine LAI appeared effective as a long-term maintenance treatment, with a safety profile generally consistent with the known profile of oral olanzapine, except for injection-related events (including post-injection delirium/sedation syndrome).

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Cholesterol; Delayed-Action Preparations; Delirium; Double-Blind Method; Female; Humans; Injections, Intramuscular; International Cooperation; Male; Middle Aged; Olanzapine; Psychotic Disorders; Quality of Life; Schizophrenia; Treatment Outcome; Triglycerides; Young Adult

A wide variability in the approach towards delirium prevention and treatment in the critically ill results from the dearth of prospective randomised studies.. We launched a two-stage prospective observational study to assess delirium epidemiology, risk factors and impact on patient outcome, by enrolling all patients admitted to our Intensive Care Unit (ICU) over a year. The first step - from January to June 2008 was the observational phase, whereas the second one from July to December 2008 was interventional. All the patients admitted to our ICU were recruited but those with pre-existing cognitive disorders, dementia, psychosis and disability after stroke were excluded from the data analysis. Delirium assessment was performed according with Confusion Assessment Method for the ICU twice per day after sedation interruption. During phase 2, patients underwent both a re-orientation strategy and environmental, acoustic and visual stimulation.. We admitted a total of respectively 170 (I-ph) and 144 patients (II-ph). The delirium occurrence was significantly lower in (II-ph) 22% vs. 35% in (I-ph) (P=0.020). A Cox's Proportional Hazard model found the applied reorientation strategy as the strongest protective predictors of delirium: (HR 0.504, 95% C.I. 0.313-0.890, P=0.034), whereas age (HR 1.034, 95% CI: 1.013-1.056, P=0.001) and sedation with midazolam plus opiate (HR 2.145, 95% CI: 2.247-4.032, P=0.018) were negative predictors.. A timely reorientation strategy seems to be correlated with significantly lower occurrence of delirium.

Topics: Acoustic Stimulation; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Critical Care; Critical Illness; Delirium; Female; Haloperidol; Humans; Hypnotics and Sedatives; Internal Medicine; Male; Medical Audit; Midazolam; Middle Aged; Narcotics; Olanzapine; Orientation; Photic Stimulation; Postoperative Complications; Propofol; Proportional Hazards Models; Risk Factors; Surveys and Questionnaires; Wounds and Injuries

The objective of the study was to assess the efficacy and safety of second-generation antipsychotics olanzapine and risperidone vs. haloperidol in patients of delirium admitted to medical and surgical wards.. Prospective follow-up single-blind randomized controlled trials were performed. Consecutive patients with delirium referred to the consultation-liaison psychiatry team were eligible for the study. The study sample comprised 64 patients, with 20 subjects in the haloperidol group, 21 subjects in the risperidone group and 23 subjects in the olanzapine group. A flexible dose regimen (haloperidol -0.25 to 10 mg; risperidone -0.25 to 4 mg; olanzapine -1.25 to 20 mg) was used. Delirium Rating Scale-Revised-98 (DRS-R98) was used as the primary efficacy measure, and mini mental status examination (MMSE) was used as a secondary efficacy measure.. There was no significant difference in mean baseline DRS-R98 severity scores and MMSE scores between the three groups. However, there were a significant reduction in DRS-R98 severity scores and a significant improvement in MMSE scores over the period of 6 days, but there was no difference between the three groups. Four patients in the haloperidol group, six subjects in the risperidone group and two subjects in the olanzapine group experienced some side effects.. Risperidone and olanzapine are as efficacious as haloperidol in the treatment of delirium.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Delirium; Drug Administration Schedule; Female; Follow-Up Studies; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Risperidone; Single-Blind Method; Treatment Outcome

To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.. Prospective randomized trial.. Tertiary care university affiliated critical care unit.. All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.. Patients were randomized to receive either enteral olanzapine or haloperidol.. Patient's delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.. Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.. Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

Topics: Adult; Aged; Analysis of Variance; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Delirium; Haloperidol; Humans; Infusions, Parenteral; Intensive Care Units; Middle Aged; Olanzapine; Prospective Studies

Olanzapine pamoate is an intramuscular depot injection for the treatment of schizophrenia. Approximately 1.4% of patients develop a serious adverse event called post-injection delirium/sedation syndrome (PDSS), characterised by drowsiness, anticholinergic and extrapyramidal symptoms. The objective is to investigate olanzapine PDSS presentations including clinical features and treatment approach. This is a retrospective review of olanzapine PDSS patients from three toxicology units and the NSW Poisons Information Centre between 2017 and 2022. Adult patients were included if they had intramuscular olanzapine then developed PDSS criteria. Clinical symptoms, treatment, timing and length of symptoms were extracted into a preformatted Excel database. There were 18 patients included in the series, with a median age of 49 years (interquartile range [IQR]: 38-58) and male predominance (89%). Median onset time post injection was 30 min (IQR: 11-38). PDSS symptoms predominate with drowsiness, confusion and dysarthria. Median length of symptoms was 24 h (IQR: 20-54). Most common treatment included supportive care without any pharmacological intervention (n = 10), benzodiazepine (n = 4) and benztropine (n = 3). In one case, bromocriptine and physostigmine followed by oral rivastigmine were given to manage antidopaminergic and anticholinergic symptoms respectively. This proposed treatment combination could potentially alleviate some of the symptoms but needs further studies to validate the findings. In conclusion, this case series supports the characterisation of PDSS symptomology predominantly being anticholinergic with similar onset (<1 h) and duration (<72 h). Bromocriptine is proposed to manage PDSS if patients develop severe dopamine blockade and physostigmine followed by rivastigmine for anticholinergic delirium.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bromocriptine; Delirium; Female; Humans; Male; Middle Aged; Olanzapine; Physostigmine; Rivastigmine

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delirium; Humans; Mania; Olanzapine; Treatment Outcome

Treatment with olanzapine depot is associated with a rare but potentially adverse reaction, namely post-injection delirium/sedation syndrome (PDSS), characterized by delirium and/or sedation. This is a case report of a 38-year-old male patient who developed symptoms consistent with PDSS shortly after receiving intramuscular injection of olanzapine depot. Clinicians should be aware of PDSS and observe patients for three hours after receiving the injection, measuring vitals and referring to medical care if necessary.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Humans; Injections, Intramuscular; Male; Olanzapine; Schizophrenia; Syndrome

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

Topics: Antipsychotic Agents; Benzodiazepines; Delirium; Hallucinations; Humans; Olanzapine

BACKGROUND Long-acting injectable (LAI) antipsychotics are one of the forms of therapy for severe mental illness. Post-injection delirium/sedation syndrome (PDSS) is a very rare but serious adverse effect following the application of an olanzapine in a long-acting form. The most common symptoms of the syndrome are sedation, delirium, dysarthria, ataxia, extrapyramidal symptoms, agitation, dizziness, or seizure. The predispositions, prevention, and exact mechanism of PDSS remain unclear. CASE REPORT We present a case report of a 30-year-old male patient experiencing PDSS, including the main symptoms of PDSS, diagnostic methods, olanzapine plasma concentrations, therapeutic process, and outcome. We then include a follow-up of the patient 2.5 years later. The patient did not have any long-term damage, had no disabilities, and no post-traumatic stress disorder following the event. We include information about his current medications, further use of LAI antipsychotics, and update about his everyday life. CONCLUSIONS PDSS is a life-threatening condition clinicians must be aware of, and the easiest precaution is a 3-h observation after the application of an injection. Because the predispositions, prevention, and exact mechanism of PDSS remains unclear, it is very important to report the rare cases of PDSS and conduct further research for the safety of our patients. The follow-up of the patient showed that the patient is doing well, he has no post-traumatic stress disorder following the event, and he did continue to use LAI antipsychotic medication.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Follow-Up Studies; Humans; Injections, Intramuscular; Male; Olanzapine

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

The efficacy and safety of dexmedetomidine and olanzapine for delirium control in critically ill elderly patients without ventilation or surgery are not known.. The efficacy and safety of dexmedetomidine and olanzapine for controlling delirium were evaluated in a retrospective cohort of critically illness by assessing the sedation level, drug dose/duration, combination rate with other sedatives, adverse effects, intubation rate and prognosis.. The maximum (1.61 ± 1.56 vs. 2.70 ± 1.01, p < 0.001), average (-0.57 ± 0.88 vs. 0.88 ± 0.73, p < 0.001), and minimum (-1.67 ± 1.04 vs. -1.37 ± 1.01, p = 0.014) RASS scores of 263 patients were lower after treating with dexmedetomidine than treating with olanzapine. Drug use duration (4.83 ± 2.67 days vs. 5.87 ± 3.14 days, p = 0.005) and sedative combination rates (13.56% vs. 40.00%, p = 0.003) were lower when treating with dexmedetomidine than that with olanzapine. A comparison of adverse effects between dexmedetomidine and olanzapine revealed respiratory depression (16.95% vs. 2.84%, p < 0.001), hypoxia (13.56% vs. 2.76%, p < 0.001) and hypotension (11.02% vs. 3.45%, p = 0.007). Intubation rates (22.88% vs. 12.41%, p = 0.023) and the length of hospital stay (9.30 ± 4.90 days vs. 8.83 ± 3.34 days, p < 0.001) were higher in patients treated with dexmedetomidine than that with olanzapine. Mortality rates, cognitive prognosis, and delirium recurrence rates were similar between groups. Age, severe cardiopulmonary disease, APACHE II scores, dexmedetomidine dose, minimum RASS score and sedative combination were significantly (p < 0.05) associated with the adverse effects of dexmedetomidine. Respiratory depression, hypoxia and hypotension in the olanzapine group all occurred during combination with benzodiazepines.. Dexmedetomidine achieved more satisfactory sedative effects on delirium control, but olanzapine was safer.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Cohort Studies; Critical Illness; Delirium; Dexmedetomidine; Female; Humans; Hypnotics and Sedatives; Intubation, Intratracheal; Length of Stay; Male; Olanzapine; Prognosis; Retrospective Studies; Risk Factors

Topics: Antipsychotic Agents; Brain Stem; Delirium; Humans; Intracranial Thrombosis; Male; Middle Aged; Olanzapine; Schizophrenia

Antipsychotics are a treatment option for delirium in the intensive care unit. Atypical antipsychotics are preferred over first-generation antipsychotics because of their lower incidence of extrapyramidal adverse effects. The most common such effect is akathisia or restlessness. This report describes a case of atypical antipsychotic-induced akathisia and addresses the clinical distinction between extrapyramidal movements and movements due to intensive care unit delirium.. A 56-year-old man who had a prolonged hospital stay after orthotopic liver transplant complicated by multisystem organ failure, primary graft failure requiring a second transplant, and enterocutaneous fistula developed agitated delirium on hospital day 28. Initial treatment included intravenous haloperidol and scheduled sublingual olanzapine (5 mg daily). His delirium and insomnia persisted, requiring dexmedetomidine infusion. Olanzapine dosing was increased to 10 mg daily on hospital day 34 and 15 mg daily on hospital day 45. The following day, his mentation improved; however, he exhibited asynchronous, nonrhythmic, involuntary rolling motions of his hands and choreiform gait.. Antipsychotics were immediately discontinued owing to acute akathisia. All symptoms resolved within 2 days, and the patient was transferred out of the intensive care unit on hospital day 52.. Although extrapyramidal adverse effects are less common with olanzapine than with typical antipsychotics, they sometimes occur and can mimic manifestations of delirium. Restlessness should alert the nurse to assess for possible extrapyramidal adverse effects. If they are suspected, antipsychotic medications should be reduced or discontinued to prevent progression to functional disability.

Topics: Antipsychotic Agents; Delirium; Haloperidol; Humans; Intensive Care Units; Male; Middle Aged; Olanzapine

Topics: Antipsychotic Agents; Australia; Betacoronavirus; Conscious Sedation; Coronavirus Infections; COVID-19; Databases, Factual; Delayed-Action Preparations; Delirium; Drug Monitoring; Humans; Incidence; Olanzapine; Pandemics; Pneumonia, Viral; SARS-CoV-2; Syndrome

To characterize patients treated with olanzapine pamoate in French centers and investigate the conditions of use of olanzapine pamoate in real-life treatment situation.. Data came from French sites participating in an international post-authorization safety study. In this observational study, patients diagnosed with schizophrenia were receiving commercially available olanzapine pamoate, in accordance with their physician's usual standard of care. Data were collected during routine visits within the standard course of patient care.. One hundred and thirty eight patients (male, 73.9%; mean age, 39.4 years; mean duration of disease, 12.7years) received olanzapine pamoate and were included in the study by 32 investigative psychiatrists distributed across 20 different sites (psychiatric hospitals). During the period of analysis, a total of 2975 injections of olanzapine pamoate was administered to the patients. The mean duration of olanzapine pamoate exposure was 475 days (1.3years). During follow-up, 13.8% of all patients had at least one psychiatric hospitalization, 15.9% had at least one same-day psychiatric hospitalization (information documented for 116patients), and 44.2% received at least one concomitant drug. Three cases of post-injection delirium/sedation syndrome were reported during the analysis period. Treatment emergent adverse events (incidence, 20.3%) were in line with the known profile of olanzapine.. Patients were administered olanzapine pamoate and monitored in compliance with label recommendations. The safety profile assessment of olanzapine pamoate in actual conditions was consistent with that described in clinical studies.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Delayed-Action Preparations; Delirium; Drug Therapy, Combination; Female; Follow-Up Studies; France; Health Status; Hospitalization; Humans; Male; Olanzapine; Schizophrenia; Treatment Outcome; Young Adult

Olanzapine is an atypical antipsychotic indicated for the treatment of schizophrenia and known to be effective in the management of delirium. In addition to its use for these indications olanzapine has also been used in the management of chemotherapy induced nausea and vomiting and otherwise difficult to control nausea and vomiting in palliative care settings. Although considered to be well tolerated with a lower incidence of extrapyramidal effects than first generation antipsychotics there are a small number of reports of olanzapine inducing delirium. Reported here are two cases of "probable" acute cognitive impairment following treatment of nausea with olanzapine. The cognitive impairment associated with olanzapine is probably mediated through its activity at cholinergic receptors a known risk factor for delirium particularly in the elderly.

Topics: Acute Disease; Aged; Antiemetics; Benzodiazepines; Delirium; Humans; Male; Nausea; Olanzapine

The aim was to report the occurrence of after application of olanzapine long-acting injection (OLAI) in patients with schizophrenia during one year period.. During one year period, OLAI was applied to 30 patients with schizophrenia (18 men, 12 women) who were non-adherent to previous treatment with oral olanzapine. Patients were 20-58 years of age (39 years old on average), diagnosed with SCID based on DSM-IV-TR criteria. Patients received OLAI in dosage between 210-405 mg (287±62 (mean ± SD)) every 2-4 weeks.. Out of 30 patients that received OLAI, 29 patients improved significantly without side-effects, and one patient developed post-injection delirium/sedation syndrome (PDSS). The patient's somatic condition stabilized and treatment with OLAI was discontinued due to the PDSS.. The occurrence of PDSS is not common and when it occurs, in our experience, it was reversible.

Topics: Adult; Arousal; Benzodiazepines; Consciousness Disorders; Delayed-Action Preparations; Delirium; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Schizophrenia; Schizophrenic Psychology; Syndrome; Young Adult

Topics: Aged; Antipsychotic Agents; Aortic Aneurysm; Benzodiazepines; Delirium; Haloperidol; Humans; Male; Olanzapine; Postoperative Complications; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Coma; Delirium; Humans; Injections, Intravenous; Male; Middle Aged; Olanzapine; Schizophrenia

To compare the efficacy of antipsychotics (APs) for delirium treatment in patients with cancer, 27 patients treated with 1 of the 4 APs, haloperidol (HPD), risperidone (RIS), olanzapine (OLZ), and quetiapine (QTP), were divided into 2 groups: long half-life (T1/2; HPD, RIS, and OLZ) versus short T1/2 (QTP) or the multiacting receptor-targeted APs (MARTAs; OLZ and QTP) versus the non-MARTA (HPD and RIS). The symptom severity was evaluated by the memorial delirium rating scale (MDAS) on days 0, 3, and 7 following intervention. Significant improvements in total MDAS scores were found in all groups on day 3. However, on day 7, only the short T1/2 group and MARTA group showed significant improvement. Consideration of an AP's pharmacological properties may be helpful for improving the outcomes of pharmacological delirium intervention in patients with cancer.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cross-Sectional Studies; Delirium; Female; Half-Life; Haloperidol; Humans; Male; Middle Aged; Neoplasms; Olanzapine; Quetiapine Fumarate; Risperidone; Severity of Illness Index

Topics: Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Female; Humans; Injections; Middle Aged; Olanzapine; Syndrome

Topics: Antiemetics; Antipsychotic Agents; Anxiety; Benzodiazepines; Cachexia; Delirium; Humans; Nausea; Olanzapine; Sleep Initiation and Maintenance Disorders; Vomiting

We report a case of delirium with anticholinergic symptoms in a 19-year-old female patient with schizophrenia. On the day the symptoms emerged, the patient received olanzapine long-acting injection and a higher dose of paliperidone. We observed symptoms ranging from confusion to delirium as well as some anticholinergic symptoms. The delirium lasted 24 hours and was managed by intravenous fluid substitution and oral benzodiazepines. Olanzapine pamoate, paliperidone and cannabis are central nervous system (CNS) depressants, and their combination can increase the risks of CNS depression. In this case report, we review the symptoms of delirium in a case of antipsychotic overdose and provide general guidelines for managing these symptoms. We also review possible complications in combined use of cannabis, olanzapine and paliperidone.

Topics: Antipsychotic Agents; Benzodiazepines; Cannabis; Central Nervous System; Cholinergic Antagonists; Delirium; Drug Overdose; Female; Humans; Olanzapine; Paliperidone Palmitate; Schizophrenia; Treatment Outcome; Young Adult

The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone, olanzapine, and aripiprazole in the management of delirium.. The Memorial Delirium Assessment Scale (MDAS), the Karnofsky Performance Status (KPS) scale, and a side-effect rating were recorded at baseline (T1), after 2-3 days (T2), and after 4-7 days (T3). Some 21 cases were case-matched by age, preexisting dementia, and baseline MDAS scores, and subsequently analyzed.. The baseline characteristics of the medication groups were not different: The mean age of the patients ranged from 64.0 to 69.6 years, dementia was present in between 23.8 and 28.6%, and baseline MDAS scores were 19.9 (haloperidol), 18.6 (risperidone), 19.4 (olanzapine), and 18.0 (aripiprazole). The doses of medication at T3 were 5.5 mg haloperidol, 1.3 mg risperidone, 7.1 mg olanzapine, and 18.3 mg aripiprazole. Over one week, the decline in MDAS scores between medications was equal, and no differences between individual MDAS scores existed at T2 or T3. After one week, the MDAS scores were 6.8 (haloperidol), 7.1 (risperidone), 11.7 (olanzapine), and 8.3 (aripiprazole). At T2, delirium resolution occurred in 42.9-52.4% of cases and at T3 in 61.9-85.7%; no differences in assessments between medications existed. Recorded side effects were extrapyramidal symptoms (EPSs) in haloperidol- and risperidone-managed patients (19 and 4.8%, respectively) and sedation with olanzapine (28.6%).. Haloperidol, risperidone, aripiprazole, and olanzapine were equally effective in the management of delirium; however, they differed in terms of their side-effect profile. Extrapyramidal symptoms were most frequently recorded with haloperidol, and sedation occurred most frequently with olanzapine.

Topics: Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Delirium; Dementia; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Risperidone

The post-injection olanzapine delirium/sedation syndrome (PDSS) was observed in a 60-year-old Caucasian, schizophrenic, non-smoker and underweight [body mass index (BMI), 18.2 kg/m(2) ] women after the fourth intramuscular injection of 405 mg olanzapine pamoate. Clinical symptoms of PDSS were similar to those of acute oral olanzapine intoxication. The patient received supportive treatment and recovered fully. High olanzapine concentrations in serum, with maximum level of 698 ng/mL, were confirmed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The authors wonder whether a low BMI and advanced age may predispose patients to PDSS occurrence.

Topics: Antipsychotic Agents; Benzodiazepines; Chromatography, Liquid; Delayed-Action Preparations; Delirium; Female; Humans; Injections, Intramuscular; Middle Aged; Olanzapine; Schizophrenia; Syndrome; Tandem Mass Spectrometry; Unconsciousness

Topics: Adolescent; Affective Disorders, Psychotic; Antipsychotic Agents; Antithyroid Agents; Benzodiazepines; Bipolar Disorder; Delirium; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole; Olanzapine; Psychotic Disorders; Radionuclide Imaging; Thyroid Gland; Thyroidectomy

Olanzapine long-acting injection (LAI) for the treatment of schizophrenia was associated with a cluster of symptoms termed post-injection delirium/sedation syndrome (PDSS) in a small percentage (~2%) of patients during clinical trials. The objective of this analysis was to evaluate the rate and clinical characteristics of PDSS since olanzapine LAI entered commercial use.. Cases of PDSS were identified from all reported adverse events during worldwide commercial use of olanzapine LAI through to 1 March 2014. Data sources included two ongoing post-marketing safety studies as well as spontaneously reported adverse events from routine clinical practice over a 5-year period (1 March 2009 to 1 March 2014).. A total of 338 PDSS events were identified. Of these, 91% occurred within 1 hour of injection, and 52% of these occurred within 15 minutes. None of the PDSS events in this analysis were fatal, and most resolved within 72 hours. The most common symptoms (occurring in >30% of cases) were sedation (61%), confusion (56%), dysarthria (54%), somnolence (46%), dizziness (45%) and disorientation (35%). Overall, PDSS occurred with approximately 0.07% of injections and in 0.46-1.03% of patients (reporting and incidence rates from spontaneous reports and post-marketing safety studies, respectively).. The PDSS events reported during routine clinical use of olanzapine LAI are generally similar in incidence and presentation to those reported in clinical trials. Caution should be applied when interpreting spontaneously reported rates of adverse events, however, due to potential under-reporting. Implemented risk-minimisation activities may contribute substantially to the identification and appropriate management of patients with PDSS in clinical practice.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Disorders of Excessive Somnolence; Dizziness; Dysarthria; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Risk Factors; Schizophrenia; Syndrome; Unconsciousness

The purpose of the study was to determine the downstream implications of atypical antipsychotic (AAP) prescribing in the intensive care unit (ICU), including discharge prescribing practices, monitoring, and attributable adverse drug events.. This retrospective cohort study included patients at least 18 years of age admitted to an ICU that received at least 2 doses of an AAP for documented delirium or avoidance of a deliriogenic medication. Exclusion criteria were documentation of an AAP as a home medication or initiation for a psychiatric indication unrelated to delirium (eg, schizophrenia).. During the 8-month study period, 156 patients were included and 133 (85.2%) patients survived to hospital discharge. Of the survivors, AAP therapy was continued for 112 (84.2%) patients upon ICU transfer and for 38 (28.6%) patients upon hospital discharge. A majority of these patients had evidence of delirium resolution or no indication for continuation documented at discharge. Of the 127 patients with an electrocardiogram ordered during AAP therapy, QTc prolongation occurred in 49 (31.4%) patients. An adverse drug event leading to drug discontinuation was documented in 16 (10.2%) patients.. Because of significant patient-centered implications, AAPs initiated in the ICU require continued evaluation for indication to avoid prolonged and possibly unnecessary use.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Delirium; Disorders of Excessive Somnolence; Female; Humans; Inappropriate Prescribing; Intensive Care Units; Male; Middle Aged; Olanzapine; Patient Discharge; Piperazines; Quetiapine Fumarate; Retrospective Studies; Risperidone; Survivors; Thiazoles

Depot antipsychotics are a treatment option for medication nonadherence in patients with schizophrenia. Nonadherence can lead to increased relapse and hospitalization rates. This article reports hospitalization data before and after initiation of olanzapine long-acting injection (LAI), a depot antipsychotic.. Data were assessed from an ongoing, multinational, prospective, observational post-authorisation safety study being conducted to evaluate post-injection delirium/sedation syndrome (PDSS), an adverse reaction that can occur following injection of olanzapine LAI. Eligible patients were aged ≥18 years, diagnosed with schizophrenia, were prescribed olanzapine LAI, and lived outside the United States. Psychiatric hospitalization and medication data were collected retrospectively for the 6-month period before study entry and prospectively throughout the study. Paired t-tests and McNemar's tests were used to assess changes in hospitalization incidence and duration. Stepwise Cox proportional hazards models assessed factors associated with hospitalizations. Analyses were based on data from the first 3 years of the continuously enrolling study (N = 668).. The average duration of olanzapine LAI exposure for all patients was 0.768 years. Of the 529 patients who received at least 1 injection of olanzapine LAI and were not hospitalized at study entry, 8.1% had at least 1 subsequent psychiatric hospitalization with a mean duration of 2.0 days. Of the 288 patients who had a >6-month follow-up, 8.3% had at least 1 post-baseline psychiatric hospitalization with a mean duration of 2.3 days. The incidence of hospitalizations in the 6-month period after treatment was significantly lower than that in the 6-month period prior to treatment (8.3 vs 32.6%, respectively; P < 0.001). Furthermore, mean hospitalization duration decreased from 11.5 days in the 6-month period before treatment to 2.3 days in the 6-month period after treatment (P < 0.001). Psychiatric hospitalization in the prior 12 months (P < 0.0001) and recreational drug use within 24 h of baseline visit (P = 0.015) were identified as potential predictors of time to first psychiatric hospitalization after beginning to take olanzapine LAI. At the time of interim analysis, 5 PDSS events had occurred, which was too few for a full analysis of those events.. Results indicate a significant reduction in the incidence and days of hospitalization from the 6-month period before to the 6-month period after olanzapine LAI initiation, which suggests reduced relapse and hospitalization during treatment. Results should be interpreted with caution due to the observational nature of the study and use of retrospective baseline data.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Female; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Length of Stay; Male; Medication Adherence; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Proportional Hazards Models; Prospective Studies; Schizophrenia; Secondary Prevention; Time Factors; United States

Topics: Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Dysarthria; Emergency Service, Hospital; Humans; Male; Middle Aged; Olanzapine; Schizophrenia; Syndrome

Depot antipsychotic injections are an important tool for the management of patients with schizophrenia who have difficulty with adherence to oral medication. However, pain and discomfort at the injection site can be a potential impediment to the use of these long-acting formulations. We report here the results of a pooled analysis of injection site-related adverse events (AEs) collected during treatment with the olanzapine long-acting injection (olanzapine LAI).. Unsolicited injection site-related AEs were pooled from 7 olanzapine LAI clinical trials conducted in patients between March 2001 and December 2010. All patients had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) or Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of schizophrenia or schizoaffective disorder and were between the ages of 18 and 75. Doses ranged from 45 to 405 mg olanzapine LAI, and injection intervals were 2, 3, or 4 weeks. Events were evaluated for severity, timing, possible risk factors, and outcome. A criterion of p < .05 for statistical significance was used for all tests.. A total of 1752 patients received at least 1 olanzapine LAI injection. Of these, 92 patients (5.3%) reported at least 1 injection site-related AE, with "pain" being the most common type (2.9%). Most events were mild (81.4%) and the median duration was 3 days. Four patients (0.2%) discontinued due to injection site-related AEs. Dose volume and body mass index did not appear to affect the probability of injection site-related AEs. However, patients who experienced a post-injection delirium/sedation syndrome event (n = 37) were more likely to have or have had an injection site-related AE at some time during the study. Incidence of injection site-related AEs appeared to decrease over time. In 94.2% of the injection site-related AEs, no specific treatment or concomitant medication was reported; in 9 cases, patients received pharmacologic treatment for reaction, mass, abscess, rash, or pain.. Injection site-related AEs with olanzapine LAI were generally mild. The incidence and nature of these injection site-related AEs were generally similar to those occurring during treatment with other injectable antipsychotics.. ClinicalTrials.gov ID; URL: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Incidence; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Pain; Psychotic Disorders; Risk Factors; Schizophrenia; Young Adult

The PDSS is a potential side-effect of the intramuscular injection of olanzapine pamoate. We saw the typical symptoms develop in a 46-year-old man 4 hours after the injection. The syndrome is caused by a toxic concentration of olanzapine, and is possibly the result of the direct injection of the substance in the bloodstream. The most important measures that can be taken to prevent such an emergency are: a careful injection procedure, a 3-hour observation period following the injection and good counselling of the patient and his family. The treatment is conservative.

Topics: Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Schizophrenia; Syndrome; Treatment Outcome

Physostigmine effectively reverses anticholinergic delirium. However, continuous IV infusion of physostigmine is rarely used due to concern for cardiotoxicity and signs of cholinergic excess such as seizures, nausea, and vomiting. We report the successful use of continuous IV physostigmine in a 6-year-old boy with anticholinergic delirium. A 6-year-old, 30-kg boy with attention deficit hyperactivity disorder (ADHD) ingested 15-20 olanzapine (5 mg) tablets. He was agitated and was treated with lorazepam at a local hospital. His heart rate was 148 beats per min; respiratory rate, 32 breaths per minute; blood pressure, 111/70 mmHg; temperature, 96.8°F, and O2 saturation of 98% on room air. His pupils were 5-6 mm, and his skin was warm and initially flushed. Blood chemistry results were normal. A 12-lead ECG showed sinus tachycardia with normal QRS and QT intervals. The agitation worsened and did not respond to benzodiazepines. The patient was then given a dose of 0.6 mg physostigmine (0.02 mg/kg) intravenously with reversal of the agitation. But the effect only lasted 45 min requiring administration of a second bolus of 0.6 mg (0.02 mg/kg). A physostigmine intravenous infusion was administered at a rate of 0.5 mg/h (0.0167 mg/kg/h). Overnight, the patient became more agitated. The physostigmine was discontinued, and IV dexmedetomidine (0.2 μg/kg/h) was started at 21:00. The patient became over-sedated with pinpoint pupils resulting in discontinuation of the dexmedetomidine at 04:00. The patient again became agitated and developed visual hallucinations. Three 1-mg (0.03 mg/kg) boluses of physostigmine were administered over 45 min, and the physostigmine infusion was restarted at a rate of 1 mg/h (0.03 mg/kg/h) for 16.5 h. He received 19.5 mg of physostigmine with no return of anticholinergic symptoms and no signs of cholinergic excess except for a tremor that resolved when the infusion was stopped. He was discharged home without further sequelae. There are few publications describing a continuous infusion of physostigmine to reverse anticholinergic delirium. Our patient received a total dose of 25.5 mg with complete resolution of symptoms. We report the successful use of continuous infusion of physostigmine to reverse anticholinergic delirium in a pediatric patient who unintentionally ingested olanzapine.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Child; Cholinesterase Inhibitors; Delirium; Drug Overdose; Heart Rate; Humans; Infusions, Intravenous; Male; Olanzapine; Physostigmine

Atypical antipsychotics have been documented to be effective in the management of delirium in adults and older children, but despite considerable need, their use has been less studied in the very young. A retrospective chart review was undertaken to describe the use of atypical antipsychotics in controlling symptoms of delirium in infants and toddlers.. All psychiatric inpatient consultations performed during a 3 year period were reviewed to identify children <36 months old diagnosed with delirium. Delirium Rating Scale (DRS) scores were retrospectively calculated when the antipsychotic was initiated and discontinued, to confirm the diagnosis of delirium and evaluate symptom severity, and then to assess symptom response to pharmacologic intervention.. There were 10 boys and 9 girls in the study population (ages 7-30 months, mean 20.5 months). Olanzapine (n=16) and risperidone (n=3) were used, and length of treatment and response were comparable for both medications. Mean DRS scores decreased significantly (p<0.001) with antipsychotic administration, without significant adverse side effects.. Although randomized placebo controlled studies are needed to better characterize the indications, risks, and benefits, these atypical antipsychotic medications appeared to be effective and safe for managing delirium symptoms in very young pediatric patients.

Topics: Antipsychotic Agents; Benzodiazepines; Child, Preschool; Delirium; Female; Humans; Infant; Male; Olanzapine; Psychiatric Status Rating Scales; Retrospective Studies; Risperidone; Severity of Illness Index; Time Factors; Treatment Outcome

Recommended doses for olanzapine long-acting injection (olanzapine LAI) are 150 mg/2 weeks, 210 mg/2 weeks, 300 mg/2 or 4 weeks, and 405 mg/4 weeks. This analysis evaluated the dosing and interval patterns to compare the actual dosing patterns with the recommended dosing strategy.. These data, from March 2010 through September 2011, were collected as part of a Risk Evaluation and Mitigation Strategy mandatory patient registry that captures all post-approval olanzapine injections in the US. This registry includes both active and inactive (60 + days since last injection) patients.. All patients with at least one olanzapine injection were included (n = 1694). The mean number of injections received was 6.6 (range of 1-40). The most frequent numbers of injections were one (26.3%) and two (12.9%). For the 11,228 olanzapine injections, the most common doses were 300 mg and 405 mg, accounting for 92.9% of injections. Although the most common time intervals between injections was about 14 days for 150 mg, 210 mg, and 300 mg, and about 28 days for 405 mg, the intervals ranged from less than 10 to more than 60 days for all doses. Among active patients (48.2% of registry), 68.2% had >120 days of treatment with any dose, and the number of days since the last injection was around 2 weeks or less for 61.2% of patients, around 3 weeks for 16.5% of patients, and around 4 weeks for 7.1% of patients. Among inactive patients (51.8% of registry), 48.6% had <30 days of treatment. For the pattern of the first five injections, most patients (70.9%) received four subsequent injections of the same dose as their initial injection.. This registry will continue to change. There is a broad range in time between injections. Most patients continue to receive the same initial dose instead of switching to a maintenance dose. This may suggest that some clinicians are not reassessing the dose after the initial starting dose because the patient was stabilized on olanzapine oral before beginning olanzapine long-acting injection. The study is limited by a database that does not include reasons for dose and dosing interval decisions or reasons for delaying or discontinuing treatment.

Topics: Antipsychotic Agents; Benzodiazepines; Coma; Deep Sedation; Delirium; Humans; Injections; Olanzapine; Schizophrenia; Treatment Outcome; United States

Most previous studies on the efficacy of antipsychotic medication for the treatment of delirium have reported that there is no significant difference between typical and atypical antipsychotic medications. It is known, however, that older age might be a predictor of poor response to antipsychotics in the treatment of delirium. The objective of this study was to compare the efficacy and safety of haloperidol versus three atypical antipsychotic medications (risperidone, olanzapine, and quetiapine) for the treatment of delirium with consideration of patient age.. This study was a 6-day, prospective, comparative clinical observational study of haloperidol versus atypical antipsychotic medications (risperidone, olanzapine, and quetiapine) in patients with delirium at a tertiary level hospital. The subjects were referred to the consultation-liaison psychiatric service for management of delirium and were screened before enrollment in this study. A total of 80 subjects were assigned to receive either haloperidol (N = 23), risperidone (N = 21), olanzapine (N = 18), or quetiapine (N = 18). The efficacy was evaluated using the Korean version of the Delirium Rating Scale-Revised-98 (DRS-K) and the Korean version of the Mini Mental Status Examination (K-MMSE). The safety was evaluated by the Udvalg Kliniske Undersogelser side effect rating scale.. There were no significant differences in mean DRS-K severity or K-MMSE scores among the four groups at baseline. In all groups, the DRS-K severity score decreased and the K-MMSE score increased significantly over the study period. However, there were no significant differences in the improvement of DRS-K or K-MMSE scores among the four groups. Similarly, cognitive and non-cognitive subscale DRS-K scores decreased regardless of the treatment group. The treatment response rate was lower in patients over 75 years old than in patients under 75 years old. Particularly, the response rate to olanzapine was poorer in the older age group. Fifteen subjects experienced a few adverse events, but there were no significant differences in adverse event profiles among the four groups.. Haloperidol, risperidone, olanzapine, and quetiapine were equally efficacious and safe in the treatment of delirium. However, age is a factor that needs to be considered when making a choice of antipsychotic medication for the treatment of delirium.. Clinical Research Information Service, Republic of Korea, (http://cris.nih.go.kr/cris/en/search/basic_search.jsp, Registered Trial No. KCT0000632).

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Delirium; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Quetiapine Fumarate; Risperidone; Treatment Outcome

Topics: Anticholinergic Syndrome; Antipsychotic Agents; Benzodiazepines; Cholinesterase Inhibitors; Delayed-Action Preparations; Delirium; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Olanzapine; Physostigmine; Syndrome

Atypical antipsychotics have been documented to be effective in the management of delirium in adults, but despite considerable need, their use has been less studied in pediatric patients.. A retrospective chart review was done to describe the use of atypical antipsychotics in controlling symptoms of delirium in children and adolescents.. Pharmacy records at Children's Hospital Los Angeles were reviewed to identify patients to whom antipsychotic agents were dispensed over a 24-month period. Psychiatric inpatient consultations during the same 24-month period were reviewed. Patients 1-18 years old diagnosed with delirium given antipsychotics constituted the study population. Delirium Rating Scale-Revised-98 (DRS-R98) scores were retrospectively calculated, when possible, at time antipsychotic was started to confirm the initial diagnosis of delirium and evaluate symptom severity, and again when antipsychotic was stopped, to assess symptom response.. Olanzapine (n=78), risperidone (n=13), and quetiapine (n=19) were used during the 2 years of the study. Mean patient age, length of treatment, and response were comparable for the three medications. For patients with two DRS-R98 scores available (n=75/110), mean DRS-R98 scores decreased significantly (p<0.001) with antipsychotic without significant adverse side effects.. Although randomized placebo-controlled studies are needed, atypical antipsychotic medications appeared to be effective and safe for managing delirium symptoms in pediatric patients while underlying etiology was addressed.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Child, Preschool; Delirium; Dibenzothiazepines; Female; Hospitals, Pediatric; Humans; Infant; Los Angeles; Male; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risperidone; Severity of Illness Index; Treatment Outcome

Topics: Aged; Antineoplastic Agents, Hormonal; Antipsychotic Agents; Benzodiazepines; Catatonia; Delirium; Humans; Male; Olanzapine; Prednisolone

Topics: Aged, 80 and over; Benzodiazepines; Bipolar Disorder; Delirium; Humans; Male; Olanzapine

Oral olanzapine is effective in controlling agitation in patients with delirium, but often, parenteral administration is necessary. Intramuscular (IM) olanzapine is approved for managing agitation in schizophrenia, but this route is inappropriate for terminally ill patients.. The purpose of this pilot study was to determine the safety and tolerability of subcutaneous (SC) olanzapine in the management of hyperactive or mixed delirium in patients with advanced cancer.. We conducted a prospective open-label study in patients with advanced cancer who had agitated delirium (Richmond Agitation Sedation Scale [RASS] score ≥+1) that had not responded to a 10mg or higher dose of parenteral haloperidol over 24 hours. Patients received olanzapine 5mg SC every eight hours for three days and continued haloperidol for breakthrough agitation. For patients requiring more than 8mg of rescue haloperidol daily, the olanzapine dose was increased to 10mg SC every eight hours. Injection site, systemic toxicity, and efficacy (RASS score <+1 and total haloperidol dose <8mg per 24 hours on the last study day) were evaluated.. Twenty-four patients received at least one olanzapine injection, and 15 (63%) completed the study. Median age of evaluable patients was 58 years (range 49-79), and 67% were males. No injection site toxicity was observed after 167 injections. Probable systemic toxic effects were observed in four patients (severe hypotension [blood pressure <90/50mmHg], paradoxical agitation, diabetes insipidus, and seizure). Efficacy was achieved in nine (37.5%) patients.. IM olanzapine is well tolerated subcutaneously. Further research is needed to evaluate its efficacy in controlling agitated delirium.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Delirium; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Olanzapine; Prospective Studies; Treatment Outcome

Topics: Aged; Alzheimer Disease; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Delirium; Depressive Disorder; Diagnosis, Differential; Dibenzothiazepines; Hallucinations; Humans; Male; Olanzapine; Oxazepam; Psychotic Disorders; Quetiapine Fumarate; Tachycardia

To describe the spectrum of clinical effects in olanzapine overdose and investigate the factors that predict severe outcomes. We analysed olanzapine-overdose events confirmed by drug analysis. Demographic, clinical and outcome data were recorded for each presentation. The relationship between dose and therapeutic olanzapine use, and outcomes (length of hospital stay, intensive care unit admission, mechanical ventilation, Glasgow coma score <9 and delirium) were investigated. Thirty-seven olanzapine overdose admissions were included. Median age was 30 years (interquartile range: 24-40 years), 24 women and 27 taking olanzapine therapeutically. Median ingested dose was 150 mg (range: 10-1600 mg). Olanzapine overdose was characterized by tachycardia (73%), central nervous system depression (43%), miosis (39%) and delirium (54%), which were either present on admission or developed within 6 h. There was no relationship between the dose and length of hospital stay, intensive care unit admission, Glasgow coma score <9 or delirium, but there was a trend towards more severe outcomes in patients not taking olanzapine therapeutically. Patients with delirium had an increased length of hospital stay and intensive care unit admission rate (50%) and 70% of them required physical or chemical restraint. Olanzapine overdose causes a high rate of delirium and central nervous system sedation that requires significant inpatient resources. Olanzapine overdoses should be initially observed for 6 h and patients not taking olanzapine regularly may have more severe effects.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain; Central Nervous System Depressants; Critical Care; Delirium; Dose-Response Relationship, Drug; Drug Overdose; Female; Glasgow Coma Scale; Humans; Length of Stay; Male; Middle Aged; Miosis; Olanzapine

To report a case of delirium probably caused by the atypical antipsychotic olanzapine in a 74-year-old man with dementia.. A 74-year-old white man with a diagnosis of severe dementia of mixed etiology with behavioral disturbances was admitted to an urban teaching hospital for increasing agitation in the context of worsening dementia. Olanzapine 2.5 mg each evening was started for agitation, and the dose was titrated to 5 mg each evening with additional emergent doses. Memantine, an N-methyl-D-aspartate antagonist, was increased from the admission dose of 10 mg/day to 15 mg/day. The patient developed symptoms of delirium on hospital day 4. Neuroleptic malignant syndrome and other causes of delirium were ruled out. Discontinuation of olanzapine resulted in resolution of the delirium.. Antipsychotic medications are commonly used to treat symptoms of delirium. Atypical antipsychotics are better tolerated in the elderly because of their fewer adverse reactions compared with other antipsychotics. Olanzapine has been successfully used in the treatment of delirium. However, there have been case reports of delirium associated with olanzapine, probably related to its intrinsic anticholinergic effect. Application of the Naranjo probability scale indicated a probable relationship between the onset of delirium and the use of olanzapine in this patient. As of December 1, 2005, this was the second such report of a case in the elderly.. Although olanzapine is useful in the treatment of delirium, elderly patients treated with this drug can develop delirium and hence should be closely monitored.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Delirium; Dementia; Humans; Male; Olanzapine

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

Olanzapine is commonly prescribed to patients with schizophrenia. One retrospective study demonstrates the efficacy of physostigmine in reversing mental status changes induced by olanzapine. We report two patients with delirium due to confirmed olanzapine overdose treated with physostigmine. One patient's mental status transiently returned to normal. The other patient completely recovered. CASE 1: A 25-year-old man ingested 300 mg of olanzapine. On presentation, he was agitated, delirious, tachycardic, had dry skin and mucous membranes, and dilated pupils (6 mm) minimally reactive to light. Physostigmine, 0.5 mg, was given intravenously (IV) without effect. Additional physostigmine doses of 1.5 mg IV administered 5 minutes later and then 1 mg IV resulted in the patient having a clear sensorium and normal mentation. The patient's mental status continued to remain normal for the duration of his hospital stay. Olanzapine was identified in the urine by high performance liquid chromatography. CASE 2: A 20-year-old female ingested 600 mg of olanzapine. On presentation, she was tachycardic, obtunded, and minimally responsive to painful stimuli, with decreased bowel sounds, dry skin and dry mucous membranes. Physostigmine, 2 mg, was given IV. Shortly thereafter she regained full consciousness and began speaking coherently. She remained in this condition for approximately 30 minutes, and then became obtunded. Her serum olanzapine concentration was 1230 ng/mL. No further doses of physostigmine were administered. On day 3 of admission her mental status returned to normal.. We report two cases of olanzapine-induced mental status changes treated with physostigmine. The utility of physostigmine as a safe or necessary antidote in the setting of olanzapine overdose remains to be determined.

Topics: Acetylcholinesterase; Adult; Benzodiazepines; Delirium; Drug Administration Schedule; Drug Overdose; Female; Humans; Injections, Intravenous; Male; Olanzapine; Physostigmine; Treatment Outcome

Topics: Antiemetics; Benzodiazepines; Delirium; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Olanzapine; Palliative Care; Terminal Care; Treatment Outcome

Topics: Aged; Analgesics, Opioid; Antiemetics; Benzodiazepines; Codeine; Delirium; Drug Interactions; Female; Humans; Middle Aged; Morphine; Olanzapine; Pain, Intractable

Elderly patients are particularly vulnerable to adverse drug reactions as a result of polypharmacy and metabolic changes associated with aging. We present a case of leukocytoclastic vasculitis induced by olanzapine, a medication commonly used in elderly patients.. An 82-year-old woman was admitted to the extended-care center for short-term rehabilitation after prolonged hospitalization for a pulmonary embolism requiring mechanical ventilation. The pulmonary problem resolved, but her hospitalization and subsequent rehabilitation were complicated by agitated delirium, which was treated with olanzapine and modification of contributory factors. At the time of admission to the rehabilitation facility, the patient had been receiving warfarin for 2 weeks and olanzapine for 6 days. On the eighth day after initiation of olanzapine, erythematous skin lesions developed on dependent areas. The international normalized ratio for warfarin was within the acceptable range; however, because warfarin has been associated with subcutaneous bleeding presenting as petechiae and ecchymosis, subcutaneous enoxaparin was substituted for warfarin. The skin lesions continued to worsen over the next week and developed into palpable lesions. Biopsy of the rash revealed leukocytoclastic vasculitis. In the absence of another cause, olanzapine was discontinued and the rash improved significantly. When the agitation recurred, risperidone was initiated, but the patient experienced dizziness with this agent. Olanzapine was resumed and the skin lesions recurred. Olanzapine was then changed to quetiapine, and the skin lesions improved over the next few weeks.. Olanzapine is commonly used in elderly patients to control behavioral disturbances associated with dementia, delirium, and other psychiatric disorders. Leukocytoclastic vasculitis is an infrequently reported adverse drug reaction with olanzapine. Its exact pathogenic mechanism is unknown, but both cell-mediated and humoral immunity appear to play important roles. Because drug-induced vasculitis has an identical clinical presentation and identical serologic/pathologic parameters to idiopathic forms of vasculitis, a high index of suspicion is necessary for its accurate diagnosis.. Because adverse drug reactions are common in elderly patients taking multiple medications, physicians should be vigilant when starting new medications and should attempt to eliminate unnecessary medications. Clinicians should be aware of the potential for leukocytoclastic vasculitis in association with olanzapine.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Delirium; Drug Eruptions; Female; Humans; Olanzapine; Pulmonary Embolism; Respiration, Artificial; Skin; Vasculitis, Leukocytoclastic, Cutaneous

Neuroleptic malignant syndrome (NMS) is a rare syndrome with four main symptoms: rigidity, hyperthermia, altered mental status and autonomic instability. We report a patient with an atypical manifestation of NMS.. A single case was reported.. A patient with pneumonia developed delirium and was treated with olanzapine and developed a NMS with fluctuating hyperthermia and autonomic instability during a month. Only slight rigidity was present. Creatine kinase was not elevated. The patient was severely agitated and manic. After discontinuation of olanzapine the patient showed no psychopathology or hyperthermia.. NMS should be considered when patients treated with antipsychotics develop one or more symptoms of NMS.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Female; Humans; Neuroleptic Malignant Syndrome; Olanzapine

We report an elderly patient who developed severe delirium and extrapyramidal signs after initiation of lithium-olanzapine combination. On hospital admission, serum levels of lithium were found to be 3.0 mM/L which were far above toxic level. Immediate discontinuation of both drugs resulted in complete resolution of most of the symptoms except for perioral dyskinesia which persisted for three more months. We critically discussed the differential diagnosis of lithium intoxication and assessed confounding factors which induce delirium and extrapyramidal signs related with combination therapy of lithium and olanzapine.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Delirium; Drug Therapy, Combination; Female; Humans; Lithium; Middle Aged; Olanzapine

Topics: Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delirium; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Olanzapine

Topics: Antipsychotic Agents; Benzodiazepines; Critical Illness; Delirium; Haloperidol; Humans; Olanzapine; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Female; Humans; Olanzapine; Parkinsonian Disorders

Topics: Antiemetics; Benzodiazepines; Delirium; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Olanzapine; Palliative Care; Terminal Care

The use of typical neuroleptics has always been the mainstay of treatment for delirium following traumatic brain injury (TBI). Given the recent application of atypical neuroleptics to various psychiatric conditions formerly treated with typical neuroleptics, one questions whether this new class of drugs is superior to its predecessor in treating delirium post-TBI. We present a case of one patient with TBI-induced delirium where in fact the use of the typical mid-potency neuroleptic, loxapine, appeared to have a better clinical effect over the atypical neuroleptic, olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain Injuries; Delirium; Humans; Loxapine; Male; Olanzapine; Pirenzepine

We describe a case of delirium due to olanzapine overdose. After ingestion of 280 mg of olanzapine, a 19-year-old schizophrenic patient developed a delirium (ICD-10: F 05.0) with consciousness disturbance, disorientation in time, space, and situation, acoustic and visual hallucinations, and agitation. The symptoms lasted for approximately 36 h. Blood pressure, temperature, and heart frequency showed no disturbance. There were no abnormalities in ECG, EEG, or routine blood tests. Approximately 36 h after the intoxication, the patient recovered fully. Until now, there have been no reports of delirium from this cause.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Drug Overdose; Female; Humans; Olanzapine; Schizophrenia

This study was performed to assess the efficacy and safety of olanzapine for the treatment of delirium in a Korean population. An open trial of olanzapine was conducted in Korean patients with delirium caused by multiple medicosurgical conditions. All subjects were evaluated by Delirium Rating Scale (DRS), which is known to be one of the most sensitive scales for delirium. In addition, other data for profiles of side-effects were collected and analyzed. Twenty patients were treated by olanzapine with doses of 5.9 +/- 1.5 mg/day. The initial dose was 4.6 +/- 0.9 mg/day and maximal dose of olanzapine was 8.8 +/- 2.2 mg/day. The average duration of treatment was 6.6 +/- 1.7 days and the day of maximal response was 3.8 +/- 1.7 treated days. The scores of DRS were significantly improved from 20.0 +/- 3.6 at the time of pretreatment to 9.3 +/- 4.6 at the post-treatment. All subjects showed no definite serious side-effects including anticholinergic and extrapyramidal symptoms. Olanzapine treatment for patients with delirium was effective and safe. This newer drug may be a useful alternative agent to classical antipsychotics in the treatment of delirium.

Topics: Adult; Aged; Benzodiazepines; Cross-Cultural Comparison; Delirium; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Korea; Male; Middle Aged; Olanzapine; Pirenzepine; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Critical Care; Delirium; Humans; Male; Middle Aged; Olanzapine; Pirenzepine