Successful treatment with quetiapine for delirium in terminally ill cancer patients

We describe six patients with terminal cancer whose delirium improved after they started quetiapine (QTP). Haloperidol (HPD) had failed to improve their delirium, and they had suffered adverse effects, including over‐sedation, extrapyramidal signs and dysphagia. We prescribed QTP to improve their delirium. We evaluated the severity of the delirium using the Japanese version of the Memorial Delirium Assessment Scale (jMDAS) before QTP treatment and 3, 7 and 14 days after QTP administration. The basal the Japanese version of the Memorial Delirium Assessment Scale score ranged from 18 to 24. Effective doses of QTP in the present cases were 12.5–50 mg/day. Delirium improved in all patients, and no significant adverse effects were observed. Several factors appear to contribute to symptoms of delirium in patients with terminal cancer. These causative factors are usually complicated and delirium often is refractory to usual pharmacotherapy, involving typical neuroleptics like HPD. QTP, however, appeared to be useful for delirium treatment in patients with advanced cancer.     

Perospirone in the treatment of patients with delirium

Perospirone is a recently developed atypical antipsychotic with potent serotonin 5-HT2 and dopamine D2 antagonist activity. Other atypical antipsychotics including risperidone, quetiapine and olanzapine have been widely used for treatment, not only for schizophrenia symptoms but also for delirium, because of their low potential to induce extrapyramidal disturbances. In the present study the effectiveness and safety of perospirone in patients with delirium are described. Thirty-eight patients with DSM-IV delirium were given open-label perospirone. To evaluate the usefulness of perospirone, scores from 13 severity items of the Delirium Rating Scale-Revised-98 were assessed. Data were gathered from October 2003 to September 2004. Perospirone was effective in 86.8% (33/38) of patients, and the effect appeared within several days (5.1 +/- 4.9 days). The initial dose was 6.5 +/- 3.7 mg/day and maximum dose of perospirone was 10.0 +/- 5.3 mg/day. There were no serious adverse effects. However, increased fatigue (15.2%), sleepiness (6.1%), akathisia (3.0%) and a decline in blood pressure (3.0%) were observed. It is proposed that perospirone may be another safe and effective atypical antipsychotic drug for the treatment of delirium symptoms in hospitalized patients. This is a preliminary open trial, and further randomized double-blind placebo-controlled tests are needed.     

Atypical antipsychotics in the treatment of delirium

Delirium is common in all medical settings. Atypical antipsychotics are increasingly used for the management of delirium symptomatology but their effectiveness has not been systematically studied. The aim of the present study was therefore to provide an up-to-date review on the use of atypical antipsychotics in the treatment of delirium. A search was conducted of the databases of MEDLINE, PsycINFO and EMBASE from 1997 to 2008 for English-language articles using the key words 'delirium' and the names of all the atypical antipsychotics. A total of 23 studies were used for this review. Fifteen of the studies were single-agent trials. Four studies were comparison trials, including one double-blind trial, and four studies were retrospective, including three comparison studies. All studies reported improvement of delirium symptomatology after the administration of atypical antipsychotics. No study included a placebo group. Other limitations included sample heterogeneity, small sample size, different rating scales for delirium, and lack of adequate controls. The improvement in delirium was observed within a few days after treatment initiation and the doses given were relatively low. Atypical antipsychotics were well tolerated, but safety was not evaluated systematically. Atypical antipsychotics appear to be effective and safe in symptomatic treatment of delirium but the evidence is limited and inconclusive. There are no double-blind, placebo-controlled studies assessing the efficacy and safety of these agents in delirium. Further research is needed with well-designed studies.     

Effects of low-dose quetiapine on psychotic symptoms in elderly patients with physical illnesses: Report of eight cases

Quetiapine, which is a new atypical antipsychotic agent, was administered at low doses (25–50 mg/day) for psychotic symptoms in eight elderly patients with physical illnesses. Delirium and hallucination were alleviated by the administration of low doses of quetiapine, and the cause–effect relationship between the administration and alleviation of symptoms was evident, particularly in one patient with delirium, because delirium was alleviated after administration began, was exacerbated after discontinuation of quetiapine, and was alleviated again after administration was resumed. Little improvement was observed in delusions or mood disorders. None of the patients showed exacerbation of physical symptoms or abnormalities in clinical laboratory tests. The results of this study suggest that quetiapine might be effective in reducing delirium and hallucination that often accompany physical illness in elderly people and could be used without adverse effects.     

Risperidone therapy for post-operative delirium in elderly patients

In elderly patients, post‐operative delirium can complicate the treatment of any underlying condition that requires surgical intervention. Two elderly patients who underwent surgical procedures for neoplasia developed symptoms of nocturnal delirium soon after recovery from general anesthesia. Risperidone therapy was initiated in both patients (0.5 mg/day in Case 1 and 0.2 mg/day in Case 2 ) and their mental states rapidly stabilized, enabling treatment of the underlying condition and resulting in good post‐operative progress. Both patients were discharged from hospital without symptoms. To the best of the author's knowledge, this is the first report of the successful use of risperidone in the treatment of post‐operative delirium.     

Use of aripiprazole for delirium in the elderly: a short review

The effects and tolerability of antipsychotics in delirium treatment remain controversial. Compared to other antipsychotics, aripiprazole differs in pharmacological activity because it exerts its effect as a dopamine D₂ partial agonist. The guidelines of the American Psychiatric Association rank aripiprazole highly among antipsychotics with regard to safety, and this drug is likely to be useful for delirium treatment. Here, we reviewed the efficacy and safety of aripiprazole for delirium. The results of our literature review on the efficacy and safety of delirium treatments suggest that aripiprazole is an effective treatment option for delirium in the elderly. Aripiprazole is as effective as other antipsychotics in improving delirium symptoms, and it is safer because it is less likely to cause extrapyramidal symptoms, excessive sedation, and weight gain. However, these findings are based on only a few clinical studies of elderly patients with delirium. Therefore, further investigations are necessary.     

The use of atypical antipsychotics beyond psychoses: efficacy of quetiapine in bipolar disorder

Background and rationale     

Blonanserin in the treatment of delirium

The purpose of the present study was to provide preliminary data on the usefulness and safety of blonanserin for patients with delirium in the intensive care unit (ICU). The charts of 32 consecutive patients with delirium in the ICU were retrospectively reviewed. These patients were treated with blonanserin. A total of 96.6% had reduction in Memorial Delirium Assessment Scale score. The proportion of patients with side-effects was 24.1%. Blonanserin may be effective and safe in the treatment of delirium in the ICU.     

Effect of quetiapine in psychotic Parkinson's disease patients: a double-blind labeled study of 3 months' duration.

This double-blind randomized study examined the effect of quetiapine (QTP) on drug-induced psychosis (DIP) in Parkinson's disease (PD). Conventional antipsychotic drugs are associated with adverse extrapyramidal effects. QTP is a new atypical antipsychotic drug used in the treatment of psychosis in PD. A total of 58 consecutive psychotic PD patients (mean age, 75 +/- 8.3 years; mean disease duration, 10.5 +/- 6.4 years; 29 with dementia) were randomly assigned to 2 groups: 30 were treated with QTP (mean dose, 119.2 +/- 56.4 mg) and 28 received placebo for 3 months. The motor part of the Unified Parkinson's Disease Rating Scale, the Brief Psychiatric Rating Scale, the Mini-Mental State Examination, the Hamilton Rating Scale for Depression, the Epworth Sleepiness Score, and the Clinical Global Impression Scale were administered before and during the study. No significant difference was found between the groups in all parameters. There were 32 PD patients (55%) completed the 3-month study (15 [26%] QTP and 17 [29%] placebo). Treatment was interrupted in 15 patients in the QTP and 11 in the placebo groups. This double-blind study did not show a beneficial effect of QTP for the treatment of DIP in PD. The high rate of withdrawal probably influenced the results. Larger double-blind studies are required.     

Predicting post-operative delirium in elderly patients undergoing surgery for hip fracture

Background: Delirium in elderly patients with hip fracture has a significant negative influence on the disease course. Awareness of risk factors for postoperative delirium (POD) may lead to the development of effective preventive strategies. The aims of this study were: to find patients’ features that are predictors of POD, and; to develop a model predicting the risk for POD. Patients and methods: Seventy‐seven elderly patients (81.9 years of age, SD 7.5 years) were non‐delirious prior to surgery and enrolled in the study. Delirium was diagnosed by Confusion Assessment Method and Algorrhithm. Patients’ characteristics as potential predictors of POD were analyzed by logistic regression analysis on SAS software. Results: Postoperative delirium was diagnosed in 37 patients. Use of multiple (>3) medications, lower scores on cognitive tests (<20 on Set Test and <24 on Mini‐mental Status Exam), albumin level less than 3.5 g/dL, hematocrit level less than 33% and age over 81 years were predictors of POD. A logistic regression formula including these predictors weighed by their parameter estimates can be used to calculate the probability of POD. The model had a good fit and a good predictive power. A Delirium Predicting Scale was derived based on parameter estimates of these predictors. Patients can be classified as low‐, intermediate‐ or high‐risk for POD. Conclusions: A logistic regression model, which includes patients’ age, medication history, cognitive performance measured by Set Test and Mini‐Mental Status Exam, albumin and hematocrit levels, can be used to predict risk for POD after surgical repair of fractured hip in elderly patients.     

Gender differences in challenging behaviors, management and outcomes in elderly patients with delirium

BACKGROUND: Gender differences have been reported in some common mental disorders. However, few studies have monitored gender differences in individuals with delirium. OBJECTIVE: To explore gender differences in challenging behaviors, management and outcomes in age-matched elderly patients with delirium.DESIGN, TIME AND SETTING: A retrospective cohort study was performed in the Bankstown-Lidcombe Hospital, Sydney, Australia, from October 2008 to April 2009. METHODS: Patients, aged 65-90 years, diagnosed with delirium according to the International Classification of Diseases (ICD)-10 in the Psychogeriatric Unit of Bankstown Lidcombe Hospital from January 2002 to October 2008 were reviewed. All the patients were measured according to the Confusion Assessment Method upon admission. Those who developed delirium during hospitalization were excluded.MAIN OUTCOME MEASURES: Cause of delirium, wandering, aggression, duration of delirium, physical restraint, use of antipsychotic medicine, recovery from delirium, discharge back home, length of stay, one-to-one nursing care, falls and absconding rate.RESULTS: The 131 age-matched delirious patients comprised 54 males and 77 females. The behavioral disorders of wandering [odds ration (OR) = 2.612, 95% confidence interval (CI) = 1.26 -5.413, P = 0.009] and aggression (OR = 2.243, 95% CI = 1.028 - 4.891, P= 0.04) were more frequent in males than in females. More males received one-to-one nursing care (OR = 4.114, 95% CI = 1.355 - 12.491, P = 0.008), were more likely to receive antipsychotic medications (OR = 2.24, 95% CI = 1.095-4.583, P = 0.021) and more likely to be physically restrained (OR = 2.07, 95% CI = 1.02-1.02, P = 0.043) compared with female patients. All absconding patients (3/131, 2.3%) were male. In addition, male patients displayed a greater falling rate compared with females (OR = 4.57, 95% CI= 1.519-13.722, P = 0.004).CONCLUSION: There are gender differences in challenging behaviors, management and outcomes in elderly delirious patients. Males with delirium display more challenging behaviors that require physical restraint and pharmacological management including wandering and aggression; males also abscond and have a higher rate of falls compared with female patients.     

Cognitive effects of quetiapine in a patient with dementia with Lewy bodies

A recent large‐scale randomized controlled clinical trial, the Clinical Antipsychotic Trials of Intervention Effectiveness‐Alzheimer's Disease study, found a significant worsening of cognitive functioning in a sample of patients with Alzheimer's disease. To date there have been no equally powered studies examining the cognitive effects of atypical antipsychotics in patients with dementia with Lewy bodies, the second most prevalent neurodegenerative disorder. This case report describes a significant cognitive improvement observed through the use of an atypical antipsychotic in a patient with dementia with Lewy bodies. The observed divergence in cognitive responsiveness is discussed mechanistically on both the clinical and neuromolecular level. Limitations to this case study design are presented and discussed. The prudence of caution in importing the results of the Clinical Antipsychotic Trials of Intervention Effectiveness‐Alzheimer's Disease study to the dementia with Lewy bodies population is summarized and presented for psychiatrists, neurologists and primary care providers, with an intent to stimulate discussion and further research.     

Efficacy of risperidone in the treatment of delirium in elderly patients

Background:  Despite increasing recognition of delirium as a serious complication of physical illness, little has been reported in this area. Interest has been raised in treatment options other than haloperidol, such as atypical antipsychotic agents.
Methods:  A 2-week open-label trial of risperidone for the treatment of delirium was conducted to assess the efficacy and tolerance of this medication in elderly patients. Twenty-two patients with DSM-IV-defined delirium were investigated. All patients had the hyperactive–hyperalert variant of delirium. Patients received a fixed dose of risperidone (mean 1.5 ± 0.7 mg; range 0.5–3 mg). Delirium was assessed using the Delirium Rating Scale (DRS) at baseline and on Days 1, 3, 5, 7, and 14 after the initiation of risperidone treatment. Clinical and demographic data, as well as risperidone therapy related information, were collected.
Results:  Delirium resolved in all patients over the course of treatment. The mean period over which delirium resolved was 4.0 ± 2.9 days. The mean DRS score at baseline was 20.7 ± 3.0. The DRS score improved from baseline to Day 1 of treatment and continued to improve until the study end-point. Mild side-effects were present in 27.3% of patients. Stepwise logistic regression identified a decrease of 2 points or higher on the DRS on Day 1 associated with side-effects. There were no significant differences in the response to treatment with the different doses of risperidone used.
Conclusion:  Our findings indicate that low-dose risperidone (0.5–3.0 mg/day) is effective and safe for the treatment of delirium in elderly patients, and that an early response on Day 1 of treatment may be associated with side-effects in these patients.     

Clinical experience with quetiapine in elderly patients with psychotic disorders

Quetiapine fumarate is a recently marketed atypical antipsychotic medication proved to be effective in the treatment of schizophrenia and schizoaffective disorder in the younger population. There is a paucity of studies of this drug in the elderly and more data are needed on the effects of quetiapine in this population, especially those with comorbid medical illnesses. Quetiapine was used to treat seven elderly hospitalized patients between 61 and 72 years of age who manifested signs of psychosis related to schizophrenia, schizoaffective disorder, or bipolar disorder. All patients had been treated previously with conventional antipsychotics or other atypical antipsychotics. Response was assessed by observation of patient's behavior. Four patients responded to treatment; three did not respond. Positive symptoms decreased markedly in all four responders. Negative symptoms showed marked decrease in two patients and moderate decrease in one patient. Preexisting extrapyramidal symptoms (EPS) diminished in three patients. Transient hypotension, dizziness, and somnolence occurred in two patients. No other side effects were noted. No adverse consequences occurred when lithium, carbamazepine, valproic acid, or venlafaxine was given concurrently. The reduction of positive and negative symptoms of schizophrenia and lack of significant EPS and minimal sedative, hypotensive, and anticholinergic side effects indicate that quetiapine may be a safe and effective medication for the elderly.     

An open multicentre pilot study examining the safety,efficacy and tolerability of fast titrated (800 mg/day by day 4) quetiapine in the treatment of schizophrenia/schizoaffective disorder

Objective. Rapid dose escalation of quetiapine could offer prompt and effective therapy to patients requiring hospitalization for schizophrenia or schizoaffective disorder. This study evaluated the safety, tolerability, and efficacy of a rapid dose escalation of quetiapine to 800 mg/day over 4 days in patients with severe psychotic symptoms diagnosed as schizophrenia or schizoaffective disorder. Methods. In this open-label, multicenter, pilot study, 14 patients aged 18 years or older, requiring hospitalization for schizophrenia or schizoaffective disorder, received quetiapine orally twice daily for 14 days. Quetiapine was administered according to the schedule: 200, 400, 600, and 800 mg/day on the first four treatment days, followed by flexible dosing within the range 400–800 mg/day during the next 10 days. The primary endpoint was to evaluate the safety and tolerability of a fast titration of quetiapine (200, 400, 600, 800 mg/day on the first four treatment days). Effectiveness of a fast titration of quetiapine was the secondary objective of this investigation. Efficacy assessments in the intent-to-treat (ITT) population included changes in the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Severity of Illness (CGI-S) scores from Day 1 (baseline) to Day 14. Results. In 4 days 14 patients were titrated up to a dose of 800 mg/day. Ten patients were diagnosed with schizophrenia, one subject was suffering from schizoaffective disorder of the depressive type and three patients were diagnosed with schizoaffective disorder of the bipolar type. Eleven patients (79%) completed the study. Two patients discontinued the trial because of non-compliance and one patient because of a prolonged QTcB interval. Overall, 29 AEs were reported during this trial, all were considered mild or moderate in severity. During the first 7 days of the trial, 25 AEs were reported in 11 patients. The majority of AEs were considered as possibly related to the study medication. No deaths or serious adverse events were reported. Physical examination at the last trial visit revealed no clinically relevant changes versus baseline and there were no consistent changes over time in vital signs. The BARS and SAS scores indicated an improvement of EPS during the study. After 4 days of fast titration, the mean total PANSS score decreased from 92.8 at baseline to a value of 87.4, there was a further decrease to 78.2 at endpoint. This corresponds to a statistically significant decrease by 14.6 versus baseline (P<0.01). After 4 days of fast titration, the mean CGI-S score was improved from 4.7 at baseline to a value of 4.3 and improved further to 3.8 at endpoint, corresponding to a statistically significant decrease of 0.9 points versus baseline (P<0.01). Conclusion. In this study, fast titration of quetiapine to 800 mg/day over 4 days was generally well tolerated and effective in reducing psychotic symptoms in patients requiring hospitalization for schizophrenia/schizoaffective disorder.     

The utility of the clock drawing test in detection of delirium in elderly hospitalised patients

Objectives: Delirium is common neuropsychiatric condition among elderly inpatients. The clock drawing test (CDT) has been used widely as bedside screening tool in assessing cognitive impairment in elderly people. Previous studies which evaluate its usefulness in delirium reported conflicting results. The objective of this study was to evaluate the utility of CDT to detect delirium in elderly medical patients.

Method: Prospective, observational, longitudinal study. All acute medical admissions 70 years of age and above were approached within 72 hours of admission for recruitment. Patients eligible for inclusion were assessed four times, twice weekly during admission. Assessment included Confusion Assessment Method (CAM), Delirium Rating Scale (DRS-98R), Montreal Cognitive Assessment (MoCA), Acute Physiology and Chronic Health Evaluation II (APACHE) II, and CDT. Data was analysed using a linear mixed effect model.

Results: Three hundred and twenty-three assessments with the CDT were performed on 200 subjects (50% male, mean age 81.13; standard deviation: 6.45). The overall rate of delirium (CAM+) during hospitalisation was 23%. There was a significant negative correlation between the CDT and DRS-R98 scores (Pearson correlation r = ?0.618, p < 0.001), CDT and CAM (Spearman's rho = ?0.402, p < 0.001) and CDT and total MoCA score (Pearson's r = 0.767, p < 0.001). However, when the data were analysed longitudinally controlling for all the factors, we found that cognitive function and age were significant factors associated with CDT scores (p < .0001): neither the presence nor the severity of delirium had an additional significant effect on the CDT.

Conclusion: CDT score reflects cognitive impairment, independently of the presence or severity of delirium. The CDT is not a suitable test for delirium in hospitalised elderly patients.