Satoshi Asakura

Fluvoxamine treatment of generalized social anxiety disorder in Japan: a randomized double-blind, placebo-controlled study

The efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment of social anxiety disorder (SAD) has been reported in the USA and Europe. However, no clinical investigation has been done with SSRIs in Japanese patients with SAD. This study was performed to determine the effectiveness and safety of fluvoxamine for generalized SAD (GSAD) in Japanese patients. In this double-blind study, patients meeting DSM-IV criteria for GSAD were randomized to receive treatment with fluvoxamine or placebo for 10 wk. Fluvoxamine treatment was initiated at 50 mg/d, and increased by 50 mg weekly to a maximum of 150 or 300 mg/d. The primary efficacy outcome was mean change from baseline on the Liebowitz Social Anxiety Scale - Japanese Version (LSAS-J) total score. The secondary outcomes were response according to the Clinical Global Impressions - Global Improvement (CGI-I) score and three domains of the Sheehan Disability Scale (SDS; used to assess psychosocial impairment). A total of 176 fluvoxamine-treated patients and 89 placebo-treated patients were eligible for the efficacy analysis. At week 10, the fluvoxamine-treated patients had a significantly greater reduction in the LSAS-J total score compared with placebo-treated patients (p=0.0197), with significantly more fluvoxamine recipients being at least much improved on the CGI-I scale compared with placebo-treated patients (p=0.024). Fluvoxamine-treated patients also had better responses on the SDS compared with placebo-treated patients (p=0.0208). Fluvoxamine was safe and well tolerated. These results suggest that fluvoxamine is effective for the treatment of Japanese patients with GSAD.

Temperament and character profiles of Japanese university student suicide completers

OBJECTIVE The aims of this study were to investigate the personality traits of suicide completers using the Temperament and Character Inventory (TCI) scale. METHODS Newly enrolled students who enrolled at Hokkaido University in 1999-2002 and 2004-2007 completed the TCI. Among these students, twenty subjects (2 females and 18 males) later completed suicide. We compared the TCI scales of these subjects with those of 60 (6 females and 54 males) well-matched controls. The controls were matched for age, gender, university department and year of enrollment in the university. Because the number of females was too small, the statistical analyses for the TCI subscales and logistic regression analysis were performed only with the 18 males. RESULTS A univariate analysis of seven personality dimensions on the TCI revealed higher scores of harm avoidance (HA) in subjects with suicide completion (P=0.034). Analysis of the male subjects showed that suicide completers had higher scores for anticipatory worry (HA1, P=0.007) and fear of uncertainty (HA2, P=0.036) and lower scores for spiritual acceptance (ST3, P=0.038) than did the controls. A multivariate analysis, which was performed to adjust confounding factors, demonstrated significantly higher scores for HA1 among suicide completers (P=0.01, OR=1.32). CONCLUSIONS These results suggest that higher HA scores may predict suicide completion.

Neurocognitive impairments and quality of life in unemployed patients with remitted major depressive disorder.

Quality of life (QOL) has been reported to be impaired in patients with major depressive disorder (MDD), even after remission according to symptom rating scales. Although a relationship between QOL and neurocognitive dysfunction has been reported during depressive episodes, little is known about this relationship in remitted MDD patients. The aim of the present study was to investigate the relationship between QOL and neurocognitive dysfunction in patients with remitted MDD while controlling for confounding factors. Forty-three remitted MDD patients were assessed with neuropsychological tests and QOL, which was measured by a short-form 36-item health survey. The neurocognitive performances of the patients were compared with those of 43 healthy controls. We next evaluated the relationships between neurocognitive impairments, clinical factors, and QOL. Remitted MDD patients had poorer neurocognitive performances than healthy controls for psychomotor speed, attention, and verbal memory. Residual depressive symptoms were strongly associated with QOL. Delayed verbal recall was associated with general health perceptions, which are part of the QOL assessment, even after the effects of the residual depressive symptoms were considered. The results may indicate that clinicians should try to detect neurocognitive dysfunctions that may interfere with QOL using neurocognitive assessments in their daily practice.

Severity of generalized social anxiety disorder correlates with low executive functioning.

To evaluate neurocognitive functions of patients with social anxiety disorder (SAD) without comorbidity using neuropsychological assessments and to investigate the relation between neurocognitive functions and clinical severity of SAD, this study assessed 30 SAD patients (10 female, 20 male) without comorbidity and 30 healthy subjects matched on gender, education level, and age. The neuropsychological assessment consisted of the Wisconsin card sorting test (WCST), the continuous performance test, the trail-making test, the word fluency test, and the auditory verbal learning test. On the WCST, patients showed lower performance than healthy controls did. The Liebowitz Social Anxiety Scale score correlated significantly with the numbers of perseverative errors of the WCST, although the State anxiety score of State-Trait Anxiety Inventory and the Beck Depression Inventory - Second Edition score showed no correlation with neuropsychological test scores. Results show that the executive functioning of patients with SAD was low and that the low functioning correlates with the SAD symptom severity.

Temperament and character profiles of Japanese university students with depressive episodes and ideas of suicide or self-harm: A PHQ-9 screening study

OBJECTIVE The aim of our study was to reveal the personality traits of individuals with major and other depressive episodes among the young adult population. Furthermore, character traits of individuals with ideas of suicide or self-harm were also investigated in this study. METHODS The subjects of this study were 1421 university students who completed the Patient Health Questionnaire (PHQ-9) and the Temperament and Character Inventory (TCI). The subjects were divided into three separate groups: the major depressive episode group (N = 41), the other depressive episode group (N = 97), and the non-depressive controls (N = 1283). This separation was achieved using the PHQ-9 algorithm diagnosis. We compared the TCI scores using an analysis of variance. Moreover, the Cochran-Armitage trend test was used to determine the diagnosis, ideas of suicide or self-harm, and analysis of character profiles. RESULTS The major depressive episode group had significantly higher HA (P < 0.001), lower RD (P < 0.001), lower SD (P < 0.001), and lower C (P < 0.001) scores than non-depressive controls. The other depressive episode group had significantly higher HA scores (P < 0.001) and lower SD scores (P < 0.001) than non-depressive controls. The Cochran-Armitage trend test revealed that the prevalence of depressive episodes decreased as the character profiles matured (χ(2)(trend) = 57.2, P < 0.0001). The same tendency was observed in individuals who had ideas of suicide or self-harm (χ(2)(trend) = 49.3, P < 0.0001). CONCLUSION High HA and low SD scores were common personality traits among young adults with major depressive episodes. Furthermore, the immaturity of character profiles was clearly associated with depressive episodes and ideas of suicide or self-harm.

Effectiveness of suicide prevention gatekeeper-training for university administrative staff in Japan

Suicide is a leading cause of death among Japanese college and university students. Gatekeeper‐training programs have been shown to improve detection and referral of individuals who are at risk of suicide by training non‐mental‐health professional persons. However, no studies have investigated the effectiveness of such programs in university settings in Japan. The aim of this study was to investigate the effectiveness of the gatekeeper‐training program for administrative staff in Japanese universities.

The association between suicide risk and self-esteem in Japanese university students with major depressive episodes of major depressive disorder.

Background The suicide risk among young adults is related to multiple factors; therefore, it is difficult to predict and prevent suicidal behavior. Aim We conducted the present study to reveal the most important factors relating to suicidal ideation in Japanese university students with major depressive episodes (MDEs) of major depressive disorder (MDD). Methods The subjects were 30 Japanese university students who had MDEs of MDD, and were aged between 18 and 26 years old. They were divided into two groups – without suicide risk group (n=15), and with suicide risk group (n=15) – based on the results of the Mini-International Neuropsychiatric Interview. Additionally, healthy controls were recruited from the same population (n=15). All subjects completed the self-assessment scales including the Beck Depression Inventory 2nd edition (BDI-II), the Beck Hopelessness Scale (BHS), Rosenberg’s Self-Esteem Scale (RSES), and SF-36v2™ (The Medical Outcomes Study 36-item short-form health survey version 2), and they were all administered a battery of neuropsychological tests. Results The RSES score of the suicide risk group was significantly lower than the RSES score of the without suicide risk group, whereas the BDI-II score and the BHS score were not significantly different between the two groups. The mean social functioning score on the SF-36v2 of the with suicide risk group was significantly lower than that of the without suicide risk group. Conclusion The individual’s self-esteem and social functioning may play an important role in suicide risk among young adults with MDEs of MDD.

Efficacy of escitalopram in the treatment of social anxiety disorder: A meta-analysis versus placebo.

Escitalopram is the most selective of the serotonin reuptake inhibitor (SSRI) antidepressants. We conducted a meta-analysis of placebo-controlled studies where escitalopram was used to treat patients with social anxiety disorder (SAD). Data from all randomised, double-blind placebo-controlled studies in SAD with escitalopram from both specialist settings and general practice were used. Patients met the DSM-IV criteria for SAD, were ≥18 years old, and had a Liebowitz Social Anxiety Scale (LSAS) ≥60. The primary outcome measure was the estimated treatment difference in LSAS total score at Week 12. Secondary outcome measures included the estimated treatment difference in the Clinical Global Impression-Severity (CGI-S) score at Week 12. A total of 1598 patients from 3 randomised controlled trials were included in the analyses. Escitalopram (n=1061) was superior to placebo (n=537), with an estimated treatment difference on the LSAS of -9.2 points (95%CI: [-14.4; -4.0], p<0.01) (escitalopram 5mg/day), -4.6 points (95%CI: [-8.1; -1.0], p<0.01) (escitalopram 10mg/day), -10.1 points (95%CI: [-13.7; -6.5], p<0.01) (escitalopram 20mg/day) and -7.3 points (95%CI: [-12.3; -2.2], p<0.01) (escitalopram 10-20mg/day). For the CGI-S, the corresponding values were -0.55 points (95%CI: [-0.79; -0.31], p<0.01) (escitalopram 5mg/day), -0.26 points (95%CI: [-0.42; -0.10], p<0.01) (escitalopram 10mg/day), -0.48 points (95%CI: [-0.64; -0.31], p<0.01) (escitalopram 20mg/day) and -0.29 points (95%CI: [-0.51; -0.07], p<0.05) (escitalopram 10-20mg/day). The withdrawal rate due to adverse events was 7.2% for escitalopram, compared with 4.3% for placebo (p<0.05). In this meta-analysis, all doses of escitalopram showed significant superiority in efficacy versus placebo in the treatment of patients with SAD.

A randomized, double-blind, placebo-controlled study of escitalopram in patients with social anxiety disorder in Japan

Abstract Objective This randomized, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20 mg/day) in Japanese patients with social anxiety disorder (SAD). Research design and methods Patients aged 18–64 years with a primary diagnosis of DSM-IV-TR defined SAD, a Liebowitz Social Anxiety Scale Japanese version (LSAS-J) total score ≥60 and a Clinical Global Impression–Severity (CGI-S) score ≥4 at baseline were randomly assigned (1:1:1) to placebo, escitalopram 10 mg or escitalopram 20 mg. The primary endpoint was change from baseline to Week 12 in the LSAS-J total score for both escitalopram 10 mg and 20 mg versus placebo (ANCOVA, FAS, LOCF), using a hierarchical testing procedure. Pre-specified secondary endpoints included LSAS-J sensitivity analyses. Clinical trial registration This study has the www.japic.or.jp identifier: JapicCTI-121842. Results For the primary efficacy endpoint, the difference from placebo in the LSAS-J was −3.9 (p = 0.089) for escitalopram 10 mg. Since the superiority of escitalopram 10 mg over placebo was not confirmed, an analysis without multiplicity adjustment was made, which showed a difference for escitalopram 20 mg versus placebo of −9.8 (p < 0.001). In pre-specified sensitivity analyses, the difference versus placebo was −4.9 (p = 0.035) (ANCOVA, FAS, OC) and −5.0 (p = 0.028) (MMRM, FAS) (escitalopram 10 mg) and −10.1 (p < 0.001) (ANCOVA, FAS, OC) and −10.6 (p < 0.001) (MMRM, FAS) (escitalopram 20 mg). Common adverse events (incidence ≥5% and significantly different from placebo) were somnolence, nausea and ejaculation disorder. Conclusion Escitalopram was efficacious, safe and well tolerated by patients with SAD in Japan. Study limitations are discussed including patient characteristics.

Validity and reliability of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Japanese patients with bipolar disorder

In Japan, there are currently no reliable rating scales for the evaluation of subjective cognitive impairment in patients with bipolar disorder. We studied the relationship between the Japanese version of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and objective cognitive assessments in patients with bipolar disorder. We further assessed the reliability and validity of the COBRA. Forty-one patients, aged 16-64, in a remission period of bipolar disorder were recruited from Hokkaido University Hospital in Sapporo, Japan. The COBRA (Japanese version) and Frankfurt Complaint Questionnaire (FCQ), the gold standard in subjective cognitive assessment, were administered. A battery of neuropsychological tests was employed to measure objective cognitive impairment. Correlations among the COBRA, FCQ, and neuropsychological tests were determined using Spearmans correlation coefficient. The Japanese version of the COBRA had high internal consistency, good retest reliability, and concurrent validity-as indicated by a strong correlation with the FCQ. A significant correlation was also observed between the COBRA and objective cognitive measurements of processing speed. These findings are the first to demonstrate that the Japanese version of the COBRA may be clinically useful as a subjective cognitive impairment rating scale in Japanese patients with bipolar disorder.