Blonanserin in the treatment of delirium

Authors

  • Koji Kato MD,

    Corresponding author
      Koji Kato, MD, Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa 259-1143, Japan. Email: k-kato@tokai-u.jp
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  • Keigo Yamada MD,

    1. Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan
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  • Mizuki Maehara MD,

    1. Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan
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  • Fumiaki Akama MD,

    1. Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan
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  • Keitaro Kimoto MD,

    1. Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan
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  • Mai Saito MD,

    1. Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan
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  • Hiroshi Yano MD,

    1. Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan
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  • Atsushi Ichimura MD, PhD,

    1. Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan
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  • Hideo Matsumoto MD, PhD

    1. Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan
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Koji Kato, MD, Department of Psychiatry and Behavioral Science, Course of Specialized Clinical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa 259-1143, Japan. Email: k-kato@tokai-u.jp

Abstract

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.

DELIRIUM IS A common physical symptom in the intensive care unit (ICU) and is found in 80% of these 20% of inpatients.1 Critically ill patients are subject to numerous risk factors for delirium. It is a negative prognostic indicator, often leading to longer hospital stays and higher mortality.2

For the treatment of delirium, first-generation antipsychotics, such as haloperidol (HPD), work well, but reports about the efficacy of second-generation antipsychotics (SGA) have increased, and the efficacy of those such as risperidone (RIS),3 olanzapine (OLZ),4 and quetiapine5 has been reported in particular.

Blonanserin (BNS) is a novel atypical antipsychotic agent developed in Japan, which strongly interrupts dopamine D2 and a serotonin 5-HT2A receptor.

In the present study we conducted a retrospective study on BNS for the treatment of delirium in the ICU.

METHODS

Subjects and education

This was a retrospective study conducted at the Advanced Critical Care Center of Tokai University Hospital.

In this review of patient care statistics, 32 consecutive patients with delirium were treated with BNS from July 2010 to December 2010. After excluding three of the 32 patients due to benzodiazepine use, the remaining 29 patients were included in the analysis.

Dosage was adjusted according to the patients' clinical condition. Patients were evaluated according to the Memorial Delirium Assessment Scale (MDAS).6 Scores were derived before and after treatment. Psychiatric diagnoses were made according to DSM-IV-TR criteria.

Patients were excluded if they were taking any other concomitant antipsychotic medication. Patients were not excluded on the basis of the type or severity of medical illness or concomitant medications from other sources. Physical severity was divided into a serious or non-serious conditions. Patients who required a respirator were categorized as being in a serious condition.

The present study was carried out retrospectively by record review. The Institutional Review Board for Clinical Research of Tokai University School of Medicine approved the protocol for medical record review.

Statistical analysis

Continuous variables are presented as means ± SD. Continuous variables were examined using Student's t-test. In the analyses, two-tailed P < 0.05 was considered significant. spss version 18.0 for Windows (SPSS, Chicago, IL, USA) was used for data analysis.

RESULTS

Baseline patient characteristics

Mean patient age was 67.0 ± 11.9 years (Table 1). The subjects consisted of 14 men and 15 women. Regarding physical severity, 14 patients (48.3%) were in a serious condition.

Table 1.  Patient background
 n = 29
Age (years) 
 Mean ± SD67.0 ± 11.9
 Range39–85
Gender, n (%) 
 Male14 (48.3)
 Female15 (51.7)
Medical diagnosis, n (%) 
 Spinal cord injury6 (20.7)
 Cerebral hemorrhage4 (13.8)
 Acute drug intoxication4 (13.8)
 Suicide by disembowelment3 (10.3)
 Heart failure2 (6.9)
 Systemic scald2 (6.9)
 Carbon monoxide intoxication2 (6.9)
 Other disease6 (20.7)
Physical severity, n (%) 
 Serious condition14 (48.3)
 Not serious condition15 (51.7)

Drug treatment and effectiveness

The mean initial dose was 5.17 ± 1.8 mg/day and the mean maximum dose was 9.50 ± 2.1 mg/day (Table 2). MDAS sores were significantly reduced from 19.9 ± 3.2 before treatment to 5.9 ± 3.8 after treatment (P < 0.05). One patient with pneumonia had an increase in MDAS score, from 17 to 20, on day 4.

Table 2.  Medication history and MDAS score change
 Mean ± SD
  • *

    P < 0.05, versus before treatment

  • MDAS, Memorial Delirium Assessment Scale.

Initial dose (mg/day)5.17 ± 1.8
Maximum dose (mg/day)9.50 ± 2.1
Duration of treatment (days)6.89 ± 5.0
MDAS score 
 Before treatment19.9 ± 3.2
 After treatment5.9 ± 3.8*

Safety

Serious adverse events, including extra-pyramidal symptoms such as dyskinesia and dystonia, were not observed. None of the patients discontinued BNS due to adverse effects, but one patient had to stop BNS due to a lack of efficacy on day 4. Four patients, however, experienced fatigue, two experienced somnolence, and one patient experienced thirstiness. There were no consistent changes or clinically relevant abnormalities on electrocardiogram, laboratory studies or in heart rate.

DISCUSSION

We investigated the therapeutic effectiveness and safety of BNS in patients with delirium who were admitted to the ICU of the Emergency Medical Center. This is the first report of its efficacy in the ICU.

Blonanserin is an atypical antipsychotic drug indicated for use in patients with schizophrenia in Japan and Korea. This agent has a high affinity for receptors of dopamine D2 and serotonin 5-HT2A, higher for D2 than for 5-HT2A, which is different to other second-generation atypical antipsychotic drugs. BNS also has a low affinity for receptors of muscarine H1, adrenaline alpha 1 and serotonin 5-HT2C.7,8 The side-effect of oversedation occurred signifcantly less frequently in the BNS group than in the HPD group in a double-blind trial.7 The occurrence of orthostatic hypotension in the BNS group was less frequent than that in the RIS group in a randomized study comparing BNS with RIS.8 Oversedation may disturb the treatment of the physical disorder. Also, orthostatic hypotension causes drift, dizziness, and dizziness upon standing, as well as being associated with risks such as falling, a risk that is particularly increased in elderly patients. In the present study, fatigue (13.8%), somnolence (6.9%), and thirstiness (3.4%) occurred as side-effects, but oversedation, orthostatic hypotension, and grave side-effects did not develop. Based on these characteristics, BNS was thought to be effective for treating delirium in patients with severe physical disorders or elderly patients in the ICU.

The efficacy of atypical antipsychotic agents for the treatment of delirium has been reported.3–5,9 In contrast, no reports on the efficacy of SGA for delirium in the ICU have been found. The efficacy of OLZ for delirium in the ICU has been reported in a non-randomized trial.10 In the present study the MDAS scores were significantly reduced from 19.9 ± 3.2 before treatment to 5.9 ± 3.8 after treatment. BNS may be effective in the treatment of delirium in the ICU. In the present study, however, one patient stopped using BNS because respiratory status worsened and exacerbated the patient's pneumonia. In this case, it is possible that BNS was not effective, but delirium and pneumonia suddenly worsened, and the patient became seriously ill.

Delirium can be classified as hyperactive, hypoactive, or mixed type based on systematic clinical observation of hospitalized patients.11 In the present study we did not diagnose the delirium subtypes. Because the sedative effect of BNS is low, BNS may be minimally effective for hyperactive delirium when psychomotor excitability and irritation are high. Further studies are required to examine the efficacy of BNS according to the delirium subtypes.

Finally, this pilot study had several limitations, including small sample size, the decision not to diagnose delirium subtypes, lack of randomization and a control group, and clinical ratings based on a retrospective chart review.

In conclusion, 96.6% of patients improved. The mean patient age was 67.0 ± 11.9 years, indicating that many of the patients were elderly. Additionally, 48.3% of patients were in a serious condition, and physical complications were severe compared with conditions in a regular hospital. Because BNS produces little oversedation, and because orthostatic hypotension and grave side-effects did not develop during the clinical trial, BNS may be considered as effective for treating delirium in the ICU, where many patients have serious physical disorders or are of old age. This trial is a preliminary study, and further controlled studies are needed to confirm the present findings.

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