A Prospective, Open-Label, Flexible-Dose Study of Quetiapine in the Treatment of Delirium

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 12/2003; 64(11):1316-21. DOI: 10.4088/JCP.v64n1106
Source: PubMed


Delirium is an organic psychiatric syndrome characterized by fluctuating consciousness and impaired cognitive functioning. High-potency typical neuroleptics have traditionally been used as first-line drugs in the treatment of delirium. However, these drugs are frequently associated with undesirable adverse events including extrapyramidal symptoms (EPS). The purpose of the present open-label, flexible-dose study was to provide preliminary data on the usefulness and safety of quetiapine for patients with delirium.
Twelve patients with DSM-IV delirium were treated with flexible doses of open-label quetiapine (mean +/- SD dosage = 44.9 +/- 31.0 mg/day). To evaluate the usefulness and safety of quetiapine, scores from the Delirium Rating Scale, Japanese version, were assessed every day (for 1 outpatient, at least twice per week), and scores from the Mini-Mental State Examination, Japanese version, and the Drug-Induced Extrapyramidal Symptom Scale were assessed at baseline and after remission of delirium. Data were gathered from April to October 2001.
All patients achieved remission of delirium several days after starting quetiapine (mean +/- SD duration until remission = 4.8 +/- 3.5 days). Quetiapine treatment was well tolerated, and no clinically relevant change in EPS was detected.
Quetiapine may be a useful alternative to conventional neuroleptics in the treatment of delirium due to its rapid onset and relative lack of adverse events. Further double-blind, placebo-controlled studies are warranted.

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Available from: Takeshi Inoue
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    • "Our result supports the findings of previous researches with regard to the comparative efficacy of haloperidol versus three atypical antipsychotics in managing symptoms of delirium [28,32,35,36,44,57-59]. The mean daily doses of risperidone, olanzapine, and quetiapine were not largely different from those of previous studies [26,32,35,36,57,60-62]. This finding also suggests that a relatively low dose of atypical antipsychotics may be effective in managing the symptoms of delirium [26,28,32,36]. "
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    ABSTRACT: 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.Trial registration: Clinical Research Information Service, Republic of Korea, (http://cris.nih.go.kr, Registered Trial No. KCT0000632).
    Full-text · Article · Sep 2013 · BMC Psychiatry
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    • "A recent meta-analysis justified the additional use of quetiapine as evidence-based only in the treatment of generalized anxiety disorder [33]. Most of the small clinical studies used increasing doses, starting at 25 mg/day [35] [36] [37]. We could only find one Italian study with quetiapine 12.5 mg to initiate treatment in 41 patients with dementia and concomitant psychotic disorders [38]. "
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    ABSTRACT: Background: Prescription of 1/2 tablets is a widespread practice, mainly to achieve dose flexibility and to facilitate swallowing. However, tablet splitting includes several disadvantages, like destruction of galenic formulation, stability problems, and unequal amount of active ingredient that may reduce effectiveness or result in a greater risk of toxicity. Objective: To assess the rate of wrongly prescribed 1/2 tablets in discharge prescriptions at the University Hospital in Basel (UHBS, 600 beds) and to evaluate its consequences for community pharmacists. Setting: Discharge prescriptions written between January 1st and December 31st 2011 and containing the term “1/2” were extracted from the electronic patients’ data management system of the UHBS. Presence of a score line and suitability for splitting were retrieved from two official sources of drug information. Main Outcome Measure: Wrong prescription was assigned for tablets with no score line or not suitable for dose splitting. Results: Of the 36,751 discharge prescriptions that were recorded in 2011 at the UHBS, 3724 (10.1%) contained at least one prescription item with the term “1/2”. The recipient patients were on average 72.9 ± 14.8 years old (median 76 years), 50.9% were women. Of the 4517 analysed items, 49% had a corresponding lower dosage strength available on the market, making splitting unnecessary. Rate of wrongly prescribed 1/2 tablets reached 16.4% (2.8% of all prescriptions) and concerned predominantly unscored tablets. When the lack of information on splitting suitability (5.6%) and on score lines (0.5%) was taken into account, the rate reached 22.4%. Half of all wrong prescriptions could be assigned to 14 different products that were prescribed with an overall rate be-tween 3.1 and 0.2%. Quetiapine (Seroquel®) at all strengths was the most often wrongly prescribed tablet to split (3.1%; no score line), followed by atorvastatin (Sortis®) at all strengths (1.3%; no score line) and oxazepam (Seresta®) 15 mg (1.2%; with decorative score line). Conclusion: Prescribing of 1/2 tablets is common and concerns every 10th discharge prescriptions. It represents a pharmaceutical care issue, since in almost every second case, an identical drug with half the dosage strength is commercially available and a substitution could be offered by the community pharmacist. Further, one out of 5 prescribed 1/2 tablets is wrong or untraceable in the official sources of drug information and represents a safety issue. In all cases, time consuming and costly clarifications must be undertaken, ultimately the physician must be consulted, in order to modify the prescription or to dispense the prescribed 1/2 tablets as off-label use. If splitting is allowed, the patient’s cognitive and physical capacities have to be clarified and appropriate aids have to be offered, e.g. a pill splitter, in order to insure the safe use of the drug.
    Full-text · Article · Jan 2012 · International Journal of Clinical Medicine
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    • "Similarly, further guidance on dosing of atypical antipsychotics is warranted. For example, mean daily quetiapine doses used in the studies identified were approximately 50 [45], 100 [28] [30], and 200 mg [54]. These are lower than doses normally employed to treat schizophrenia. "
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    ABSTRACT: The aim of this review was to summarize and critically evaluate the current literature regarding the safety and efficacy of drug therapy in delirium. We also identified recent research developments and highlighted some ongoing clinical trials to explore future directions in drug treatment and prevention of delirium. We conducted a literature search of Medline, Embase, PsychInfo, and Cochrane Review databases, which included both prospective and retrospective clinical trials and case studies on delirium and drug therapy in adult patients up to March 2008. Abstracts from recent topical conferences were also reviewed. Ongoing delirium drug studies were identified via the WHO International Clinical Trials Registry Platform Search Portal, accessed March 12, 2008. The evidence base for effective drug treatment of delirium is restricted by limitations in many of the studies conducted to date. However, there has been an increase in the quantity and quality of delirium drug studies in recent years; preliminary reports and ongoing studies add to this trend. Although efficacy rates between typical and atypical antipsychotic agents are similar, the latter are associated with fewer extrapyramidal side effects. Prophylactic interventions with antipsychotic and cholinesterase inhibitors in high-risk patients provide an opportunity to improve postoperative patient care. Alternative techniques and medication opportunities could be explored in attempts to minimize drug induced delirium potential. Appropriate drug therapy should be considered part of systematic approaches to delirium treatment and prevention. There is a need for well-designed randomized, double-blind placebo-controlled trials investigating the drug management of various aspects of delirium, including delineating treatment by delirium subtype, dose ranging studies, and optimal duration of therapy.
    Full-text · Article · Oct 2008 · Journal of Psychosomatic Research
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