The possibility that requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia.

We examined clinical characteristics including serum olanzapine concentrations for acute schizophrenia patients who required above conventional doses. We performed a rater-blinded, randomized clinical trial in 12 psychiatric emergency sites. Eligible patients were 18-64 years old and met diagnostic criteria for schizophrenia, acute schizophrenia-like psychotic disorder, or schizoaffective disorder. A total of 42 patients were randomly assigned by means of sealed envelopes to receive risperidone (3-12 mg/day; n=20) and olanzapine (10-40 mg/day; n=22), with follow-up at 8 weeks. The Negative score of the Positive and Negative Syndrome Scale was significantly higher in patients who required high doses than in patients who responded to conventional doses. Serum olanzapine concentrations at the time of oral 20mg/day could be obtained from 5 out of 7 patients who subsequently required high-dose olanzapine. All values were more than 30 ng/mL after 11-16 h from dosing to sample collection, and the mean value was 47.876 (S.D. 21.546) ng/mL. Such concentrations are appropriate with respect to a therapeutic range of 20-50 ng/mL. The present study has shown evidence that the reason for requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia.

A comparison between augmentation with olanzapine and increased risperidone dose in acute schizophrenia patients showing early non-response to risperidone.

We examined whether augmentation with olanzapine would be superior to increased risperidone dose among acute schizophrenia patients showing early non-response to risperidone. We performed a rater-blinded, randomized controlled trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as Clinical Global Impressions-Improvement Scale score ≤3 following 2 weeks of treatment. Early non-responders were allocated to receive either augmentation with olanzapine (RIS+OLZ group) or increased risperidone dose (RIS+RIS group). The 78 patients who completed 2 weeks of treatment were divided into 52 early responders to risperidone and 26 early non-responders to risperidone (RIS+OLZ group, n=13; RIS+RIS group, n=13). No difference in the achievement of ≥50% improvement in Positive and Negative Syndrome Scale total score was observed between RIS+OLZ and RIS+RIS groups. Although time to treatment discontinuation for any cause was significantly shorter in the RIS+RIS group (6.8 weeks [95% confidence interval, 5.2-8.4]) than in early responders to risperidone (8.6 weeks [7.9-9.3]; P=0.018), there was no significant difference between the RIS+OLZ group (7.9 weeks [6.3-9.5]) and early responders to risperidone. Secondary outcomes justify the inclusion of augmentation arms in additional, larger studies comparing strategies for early non-responders.

[A case of giant thyroid tumor with tracheal stenosis].

A 61-year-old female underwent resection of a giant thyroid tumor, and tracheal stenosis ensued. She had cough, dyspnea, and palpitation in the supine position. The giant thyroid tumor was of the size of 11 x 12 cm and the diameter of trachea was 8 x 6 mm at 3.5 cm below the vocal cord, at which point the trachea was the narrowest on cervical computed tomography. The peak expiratory flow rate from the flow-volume curve was 2.94 l x sec(-1) (% predicted value 55.2%) in the upright position. We were concerned about difficult airway management. Oro-tracheal intubation with an armored tube (ID 7.5 mm) was performed after intravenous midazolam 2 mg and fentanyl 50 microg, 4% lidocaine spray 2 ml with oxygen 6 l x min(-1) inhalation keeping spontaneous breathing and consciousness. Anesthesia was induced and maintained with intravenous propofol, fentany, vecuronium and nitrous oxide in oxygen to keep the bispectral index between 40 and 60. The extracted thyroid tumor was 620 g in weight. A careful preoperative evaluation of the airway using ultrasonography, CT, MRI, laryngoscopy, bronchoscopy and respiratory function test, especially peak expiratory flow rate of the flow-volume curve is important in such a case of a giant thyroid tumor. Intubation under conscious sedation with midazolam and fentanyl is useful for a patient with a giant thyroid tumor and tracheal stenosis.