Times to Discontinue Antidepressants Over 6 Months in Patients with Major Depressive Disorder.

OBJECTIVE: The aim of the present study was to investigate differences in discontinuation time among antidepressants and total antidepressant discontinuation rate of patients with depression over a 6 month period in a naturalistic treatment setting. METHODS: We reviewed the medical records of 900 patients with major depressive disorder who were initially prescribed only one kind of antidepressant. The prescribed antidepressants and the reasons for discontinuation were surveyed at baseline and every 4 weeks during the 24 week study. We investigated the discontinuation rate and the mean time to discontinuation among six antidepressants groups. RESULTS: Mean and median overall discontinuation times were 13.8 and 12 weeks, respectively. Sertraline and escitalopram had longer discontinuation times than that of fluoxetine, and patients who used sertraline discontinued use significantly later than those taking mirtazapine. No differences in discontinuation rate were observed after 24 weeks among these antidepressants. About 73% of patients discontinued antidepressant treatment after 24 weeks. CONCLUSION: Sertraline and escitalopram tended to have longer mean times to discontinuation, although no difference in discontinuation rate was detected between antidepressants after 24 weeks. About three-quarters of patients discontinued antidepressant maintenance therapy after 24 weeks.

Adjunctive varenicline treatment for smoking reduction in patients with schizophrenia: A randomized double-blind placebo-controlled trial.

OBJECTIVES: Smoking is more common among patients with schizophrenia than it is in the general population. Varenicline, a partial and full agonist at the α4ß2 and α7 nicotine acetylcholine receptors, respectively, has been shown to be an effective anti-smoking treatment. This study examined the effects of varenicline treatment on smoking reduction in patients with schizophrenia. METHODS: Sixty smokers with schizophrenia were recruited and randomized to receive either varenicline or placebo. Smoking behavior was assessed with the Minnesota Nicotine Withdrawal Scale (mNWS), Brief Questionnaire of Smoking Urge (QSU-brief), and Modified Cigarette Evaluation Questionnaire (mCEQ). Exhaled carbon monoxide was also measured to assess smoking dependency and status. Data were analyzed with the two-tailed Student's t-test, χ(2) test, and repeated measures ANOVA. RESULTS: During the 8-week study, there was a significant time×group interaction, which showed that smoking decreased over time in the varenicline group. Expired CO levels also decreased in the varenicline group, showing a significant time effect, group effect, and time×group interaction. Total mCEQ scores decreased in the varenicline group, demonstrating a significant time×group interaction. Among the five domains of the mCEQ, the smoking satisfaction, psychological reward, and enjoyment of respiratory tract sensation domains showed significant time×group interactions in the varenicline group. The QSU-brief and mNWS demonstrated a significant time effect, but not significant time×group interactions. Adjunctive varenicline treatment with antipsychotics was generally well-tolerated and safe. CONCLUSIONS: Varenicline showed significant efficacy in reducing smoking in people with schizophrenia.

The Relationship between Language Ability and Cognitive Function in Patients with Schizophrenia.

OBJECTIVE: Cognitive dysfunction is common in people with schizophrenia, and language disability is one of the most notable cognitive deficits. This study assessed the use and comprehension ability of the Korean language in patients with schizophrenia and the correlations between language ability and cognitive function. METHODS: Eighty-six patients with schizophrenia and a group of 29 healthy controls were recruited. We assessed both clinical symptoms and cognitive functions including Korean language ability. For clinical symptoms, the Positive and Negative Syndrome Scale, Clinical Global Impression-Schizophrenia Scale, and Social and Occupational Functioning Assessment Scale were used. For the Korean language ability assessment, a portion of the Korean Broadcasting System (KBS) Korean Language Test was used. The Short-form of Korean-Wechsler Adult Intelligence Scale, the Korean version of the University of California San Diego (UCSD) Performance-based Skills Assessment (K-UPSA), and the Wisconsin Card Sorting Test (WCST) were used to assess cognitive functions. RESULTS: Schizophrenic patients had significantly lower scores in the language and cognitive function tests both in the total and subscale scores. Various clinical scores had negative correlations with reading comprehension ability of the KBS Korean Language Test. The WCST and a part of the K-UPSA had positive correlations with multiple domains of the language test. CONCLUSION: A significant difference was found between schizophrenic patients and controls in language ability. Correlations between Korean language ability and several clinical symptoms and cognitive functions were demonstrated in patients with schizophrenia. Tests of cognitive function had positive correlations with different aspects of language ability.

Differences in cognitive function and daily living skills between early- and late-stage schizophrenia.

OBJECTIVES: Cognitive dysfunction is a core feature of schizophrenia; deficits often manifest prior to diagnosis and persist throughout the course of the illness. This study was performed to assess the difference in cognitive function and daily living skills between the early- and late-stage schizophrenia. METHODS: Fifty-five clinically stable patients with schizophrenia were recruited (25 with < 5-year and 30 with > 5-year disease durations). We evaluated subjects' clinical states, cognitive function, and psychosocial factors. The Korean versions of MATRICS Consensus Cognitive Battery and UCSD Performance-based Skills Assessment were used for evaluating cognitive function and daily living skills. Chi-square, Wilcoxon rank sum, and t-tests were used to analyze the data. RESULTS: The two groups did not differ for most demographic variables. No significant differences between groups were found for clinical symptoms, psychosocial factors, or non-social cognitive domains. However, the early-stage group had higher social cognition domain scores than the late-stage group (p = 0.01). Early-stage patients scored significantly higher than those in the late-stage group did in the communication and comprehension/planning domains (p = 0.037 and 0.027, respectively), and total score (p = 0.003) of the Performance-based Skills Assessment. CONCLUSIONS: We observed significant differences between patients with early- and late-stage illness with regard to social cognition and performance-based skills.

Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: a randomized double-blind placebo-controlled trial.

The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the α4ß2 and full agonist at the α7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. In all, 120 clinically stable people with schizophrenia participated in randomized, double-blind, placebo-controlled 8-week trial. Antipsychotic and concomitant medication doses remained fixed throughout the study. Varenicline was titrated up to 1 mg twice daily for weeks 2-8. Neuropsychological, clinical, and safety assessments were administered at baseline and weeks 1, 2, 4, and 8. In the primary analyses of neurocognitive differences at week 8, no varenicline-placebo differences were significant. In secondary longitudinal analyses, varenicline improved compared with placebo on the Digital Symbol Substitution Test (p=0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p=0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p=0.008) and Stroop Interference (p=0.004) were reduced for varenicline compared with placebo, while there were no treatment differences in non-smokers. No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms. Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia. In some cases, effects of treatment varied between smokers and non-smokers. Further study is required to assess the functional significance of these changes.

Bone mineral density and osteoporosis risk in older patients with schizophrenia.

OBJECTIVE: People with schizophrenia are at a higher risk for osteoporosis. The authors investigated the prevalence of low bone density and its risk factors in older Korean patients with schizophrenia. METHOD: In cross-sectional study, 327 inpatients with schizophrenia were screened. Among them, 229 patients older than 50 years participated in this study. The control group consisted of healthy volunteers who were of similar ages (n = 125). Bone density was measured in the lumbar spine and the neck, trochanter, and ward regions of the right proximal femur by dual-energy x-ray absorptiometry. Clinical variables such as alcohol use, cigarette smoking, and fracture history were obtained. The Student t test, Pearson χ2 test, Wilcoxon rank sum test, and logistic regression analysis were used. RESULTS: The prevalence of osteoporosis was significantly higher in patients with schizophrenia compared with healthy controls (34.9% vs 18.4%, P = 0.0043). Within the schizophrenia group, female subjects had a significantly higher prevalence of osteoporosis than male subjects (48.4% vs 25.7%, P = 0.0014); however, no sex differences were identified in the healthy control group. The actual bone density and t scores in patients with schizophrenia were significantly lower in all sites than in healthy controls. Among patients with schizophrenia, smokers and alcohol abuser showed lower bone density compared with those who did not smoke or drink. The lifetime prevalence of fracture was significantly higher in patients with schizophrenia (24.0%) compared with healthy controls (5.6%; P = 0.001). CONCLUSIONS: Our results emphasize that older patients with schizophrenia are at risk for low bone density. Cigarette smoking and alcohol abuse are associated with low bone density in patients with schizophrenia.

Genetic association of BDNF val66met and GSK-3beta-50T/C polymorphisms with tardive dyskinesia.

AIMS: Neurodegenerative processes may be involved in the pathogenesis of tardive dyskinesia (TD), and a growing body of evidence suggests that brain-derived neurotrophic factor (BDNF) plays a role in both the antipsychotic effects and the pathogenesis of TD. BDNF and glycogen synthase kinase (GSK)-3beta are important in neuronal survival, and thus abnormal regulation of BDNF and GSK-3beta may contribute to TD pathophysiology. This study investigated the relationship between two polymorphisms, val66met in the BDNF coding region and -50T/C in the GSK-3beta promoter, and susceptibility to TD among a matched sample of patients having schizophrenia with TD (n = 83), patients with schizophrenia without TD (n = 78), and normal control subjects (n = 93). METHODS: All subjects were Korean. The BDNF val66met and GSK-3beta-50T/C genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analyses. RESULTS: Polymerase chain reaction analysis revealed no significant difference in the occurrence of the polymorphisms among the TD, non-TD, and control subjects, but a significant interaction was observed among the groups possessing BDNF val allele in compound genotypes (P = 0.001). We found that the schizophrenic subjects with the C/C GSK-3beta genotype, who carry the val allele of the BDNF gene, are expected to have a decreased risk of developing neuroleptic-induced tardive dyskinesia (P < 0.001). CONCLUSIONS: Our results demonstrate that the GSK-3beta C/C genotype with the BDNF val allele is associated with patients having schizophrenia without TD. This study also suggests that the BDNF and GSK-3beta gene polymorphisms work in combination, but not individually, in predisposing patients with schizophrenia to TD.

Evaluating associations between 5-HTTLPR polymorphism and Alzheimer's disease for Korean patients.

There has been growing evidence that the serotonin (5-HT) system is important in the regulation of memory and thus might be associated with Alzheimer's disease (AD), while research results on this issue have been inconsistent. The 5-HT system has also been suggested to be responsible for a significant portion of the behavioural aspects of AD. This study aimed to investigate the associations of the 5-HT transporter gene linked polymorphic region (5-HTTLPR) polymorphism with AD and delusional/aggressive symptoms of AD in Korean samples of 65 patients and 43 controls. The 5-HTTLPR polymorphism was neither associated with AD nor with delusional/aggressive symptoms of AD. It was suggested that phenotypic expression of the 5-HTTLPR polymorphism might be varied according to ethnic differences.