Kim Ch

Risperidone metabolism in relation to CYP2D6*10 allele in Korean schizophrenic patients

Objective: Risperidone is known to be biotransformed to its active metabolite, 9-hydroxyrisperidone, by the polymorphic CYP2D6 in Caucasians. This study aimed to investigate the relationship between the CYP2D6*10 allele and the plasma levels of risperidone and 9-hydroxyrisperidone in Korean schizophrenic patients. Methods: Eighty-two Korean schizophrenic patients in monotherapy with oral doses of risperidone from 1xa0mg/day to 8xa0mg/day (mean ±SD 4.3±1.9, median 4) participated in this study. Plasma concentrations of risperidone and 9-hydroxyrisperidone were analyzed using high-performance liquid chromatography. The CYP2D6*10 allele, which contains C188T mutation in exon 1, was identified using allele-specific polymerase chain reaction amplification. Results: Seventeen of 82 patients were homozygous for CYP2D6*1, 22 for *10, while the remaining 43 patients were heterozygous for these alleles. The plasma levels of risperidone and 9-hydroxyrisperidone ranged from 1.0xa0nM to 168xa0nM and 6.2xa0nM to 235xa0nM, respectively. The median concentrations/dose (C/Ds) (range) of risperidone in CYP2D6*1/*1, *1/*10, and *10/*10 groups were 1.7 (0.2–7.9), 2.6 (0.3–27.1), and 6.7xa0nM/mg (2.4–21.0), respectively. There was a statistically significant difference among the three genotypes (Kruskal-Wallis test, P<0.001). For 9-hydroxyriperidone, the corresponding median C/Ds were 13.1 (3.3–25.4), 11.9 (4.2–30.8), and 13.6xa0nM/mg (6.5–52.8), respectively, with no significant difference between the genotypes (P=0.54). The medians of the ratios between risperidone and 9-hydroxyrisperidone concentrations were 0.13 (0.01–0.93), 0.28 (0.01–2.77), and 0.46xa0nM/mg (0.05–1.28) in *1/*1, *1/*10, and *10/*10 genotypes, respectively, and they were significantly different (P=0.004). The active moieties (sum of the C/Ds of risperidone and 9-hydroxyrisperidone) were not significantly different between the genotypes (P=0.063). Conclusion: In Korean schizophrenic patients, the metabolism of risperidone is dependent on CYP2D6, and the CYP2D6*10 allele is important for the regulation of the activity of this enzyme. There were no significant differences in the plasma concentration of parent drug plus its active metabolite between the genotypes. This suggests that the clinical significance of this polymorphism is limited. Our study confirms previous studies on risperidone metabolism in Caucasians.

Segmented volumes of cerebrum and cerebellum in first episode schizophrenia with auditory hallucinations

The volumes of cerebral and cerebellar regions were measured in first episode schizophrenic patients with (n = 17) and without (n = 8) auditory hallucinations. Magnetic resonance images of cerebral and cerebellar regions were segmented into gray and white fractions using an algorithm for semiautomated fuzzy tissue segmentation. They were defined by using the semiautomated Talairach atlas-based parcellation method. Patients with auditory hallucinations showed larger temporal white matter, frontal gray matter, and temporal gray matter volumes than patients without auditory hallucinations. These findings suggest that auditory hallucinations in schizophrenic patients may be associated with neuropathological abnormalities in frontal and temporal brain regions.

Comparative Analysis of Cognitive Function in Schizophrenia with and without Obsessive Compulsive Disorder.

Objective We investigated the neurocognitive deficits in schizophrenic patients with and without obsessive-compulsive disorder (OCD). Methods We grouped 27 patients as either obsessive-compulsive or non-obsessive-compulsive based on the presence of OCD. The two groups completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Positive and Negative Symptom Scale (PANSS), and Hamilton Depression Scale. The intelligence quotient (IQ) was tested using the Korean Wechsler Adult Intelligence Scale. The memory quotient (MQ) was tested using the Korean-Auditory Verbal Learning and Korean-Complex Figure Test. The executive intelligence quotient (EIQ) was determined using the Kims executive intelligence test (EXIT). Results Ten of the 27 patients had OCD. The compulsion score of Y-BOCS was positively correlated with positive symptoms, negative symptoms, and the total scores of PANSS. The OCD-schizophrenia patients had higher IQs. No difference was found in MQ. Although the EIQ did not differ between the two groups, the OCD-schizophrenia patients performed better at the Stroop-interference and verbal fluency tests, which was highly dependent on executive function. Conclusion Our findings suggest that OCD may have a protective effect on some cognitive function, at least in relatively early stage of illness. Moreover, based on clinical, neurocognitive features, schizophrenia with OCD could be considered as a distinct subtype of schizophrenia.

Use of Aripiprazole in Clozapine Induced Enuresis: Report of Two Cases

This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately.

The effect of paliperidone extended release on subjective well-being and responses in patients with schizophrenia.

OBJECTIVEnThis study aimed to evaluate the subjective well-being and attitudes toward antipsychotic medication of patients with schizophrenia who had switched to paliperidone extended release (ER).nnnMETHODSnA total of 291 patients with schizophrenia treated with antipsychotics participated in this open-label, 24-week switching study. The primary outcome measures were the Subjective Well-Being under Neuroleptic Treatment Scale-short version (SWN-K) and the Drug Attitude Inventory (DAI). The Krawiecka scale, Clinical Global Impression-Schizophrenia (CGI-SCH), Personal and Social Performance scale (PSP) were used to evaluate psychopathology and psychosocial functioning, respectively.nnnRESULTSnData from a total of 243 subjects who received the study medication and had at least one follow-up assessment without a major protocol violation were analyzed. Scores on the DAI and SWN-K showed significant improvement between baseline and end-point measurements beginning during the second week. Scores on the Krawiecka scale, all five subscales of the CGI-SCH scale, and the PSP scale were also significantly improved at the end point compared with the baseline. Significant predictors of improvements in the SWN-K and DAI after a switch to paliperidone ER were baseline scores, reductions in scores on the Krawiecka scale, and previous risperidone use. A clinically relevant increase in body weight (≥7% weight gain) occurred in one-fourth of the participants who completed the 24-week study.nnnCONCLUSIONnSwitching to paliperidone ER improved the subjective well-being and attitudes towards antipsychotic medication in patients with schizophrenia. Exploratory analyses revealed that these improvements were particularly pronounced in patients who had been treated with risperidone before treatment with paliperidone ER.

Changes in neurocognitive function in patients with schizophrenia after starting or switching to amisulpride in comparison with the normal controls.

Abstract We examined short- and long-term changes in neurocognitive functions in patients with schizophrenia who were either started or switched to amisulpride in comparison with the normal controls. Fifty-seven patients treated with amisulpride and 60 normal controls completed a comprehensive neurocognitive function test battery at the baseline, the 8-week, and the 1-year follow-up. We conducted and compared the results of both intention-to-treat (ITT) and per-protocol (PP) analyses to account for the follow-up loss. Three general results obtained were as follows: (1) the degree of the improvements in neurocognitive function was comparable to those of other second-generation antipsychotics in both ITT and PP analysis; (2) in light of the relative effect size, the composite effect size and the effect size in most measures in both ITT and PP analyses were smaller for the patient group than those of the control group, signifying that improvement in performance may be largely attributable to practice effects; and (3) nonetheless, there were evidences of both short- and long-term improvements in some cognitive tasks, such as in the Korean-Wechsler Adult Intelligence Scale vocabulary subtest and the Trail Making Test, that may not be accounted by practice effect. These results suggest the need to include a healthy control group to validate the medication effect of cognitive improvements in patients with schizophrenia and to consider practice effect in interpreting the results of repeated administration of neurocognitive function tests.

Effectiveness of paliperidone extended-release for patients with schizophrenia: focus on subjective improvement.

This study assessed whether the subjective experience of patients with schizophrenia improved after switching from an oral antipsychotic to flexibly‐dosed paliperidone extended‐release.

Relationship between inflammation and metabolic syndrome following treatment with paliperidone for schizophrenia

OBJECTIVEnMetabolic syndrome and antipsychotic medications are associated with inflammation. This study investigated the relationship between inflammation and metabolic syndrome in patients with schizophrenia. It also examined the effects of paliperidone extended release (ER) treatment on metabolic parameters.nnnMETHODSnData were analyzed from schizophrenic patients who participated in a multi-center, open-label, non-comparative clinical trial. Anthropomorphic measurements (i.e., weight, waist circumference, and blood pressure) were assessed along with fasting laboratory values, including white blood cell (WBC) count, glucose, high-density lipoprotein, and triglycerides.nnnRESULTSnAmong the 225 patients at baseline, the group with the highest WBC count displayed a 5.9-fold risk for metabolic syndrome compared with that of the lowest group. An increase of 10(3)WBCs/μL was associated with a 1.4-fold increased risk for metabolic syndrome. After 24weeks of treatment with paliperidone ER, significant increases were observed in waist circumference and body weight. Changes in WBC count were positively correlated with changes in waist circumference.nnnCONCLUSIONSnSchizophrenic patients with high levels of inflammation should be carefully monitored for metabolic syndrome. Moreover, strategies to reduce inflammation and obesity may prevent metabolic syndrome in patients with schizophrenia who take atypical antipsychotic medication.

Factors Affecting Treatment Discontinuation and Treatment Outcome in Patients with Schizophrenia in Korea: 10-Year Follow-Up Study

Objective There have been few long-term studies that have assessed factors influencing treatment discontinuation and long-term outcome of schizophrenia in Korea. The present study aimed to evaluate factors affecting treatment discontinuation and treatment outcome, after 10 years, in patients with schizophrenia. Methods Among hospitalized patients between 1997 and 1999, 191 patients were given continuous follow-up service. We examined the clinical characteristics and outcome of patients who remained in treatment. Regression analyses were used to find any clinical factors affecting treatment discontinuation. Results One hundred thirty-three patients (71.12%) discontinued the treatment. The treatment retention group contained more female patients, paranoid-type patients, patients who had shown self-harming behavior, patients receiving clozapine, and patients with good medication compliance. The recovery rate was 25%. However, 42.3% did not have gainful employment. Further, most patients couldnt live independently. Conclusion The results show the importance of gender, patient behavior, medication, and medication compliance in predicting treatment discontinuation in patients with schizophrenia.

Influence of History of Brain Disease or Brain Trauma on Psychopathological Abnormality in Young Male in Korea : Analysis of Multiphasic Personal Inventory Test

OBJECTIVEnThe purpose of this study is to confirm whether brain disease or brain trauma actually affect psychopathology in young male group in Korea.nnnMETHODSnThe authors manually reviewed the result of Korean military multiphasic personal inventory (KMPI) in the examination of conscription in Korea from January 2008 to May 2010. There were total 237 young males in this review. Normal volunteers group (n=150) was composed of those who do not have history of brain disease or brain trauma. Brain disease group (n=33) was consisted of those with history of brain disease. Brain trauma group (n=54) was consisted of those with history of brain trauma. The results of KMPI in each group were compared.nnnRESULTSnAbnormal results of KMPI were found in both brain disease and trauma groups. In the brain disease group, higher tendencies of faking bad response, anxiety, depression, somatization, personality disorder, schizophrenic and paranoid psychopathy was observed and compared to the normal volunteers group. In the brain trauma group, higher tendencies of faking-good, depression, somatization and personality disorder was observed and compared to the normal volunteers group.nnnCONCLUSIONnYoung male with history of brain disease or brain trauma may have higher tendencies to have abnormal results of multiphasic personal inventory test compared to young male without history of brain disease or brain trauma, suggesting that damaged brain may cause psychopathology in young male group in Korea.