Shinji Fujikoshi

Efficacy of olanzapine monotherapy in the treatment of bipolar depression with mixed features

BACKGROUND This analysis investigated the correlations between the efficacy of olanzapine monotherapy and the number of concurrent manic symptoms in patients treated for bipolar depression. METHODS Pooled data from 2 placebo-controlled olanzapine studies in patients with bipolar I depression were analyzed (total 1214 patients; 690 olanzapine monotherapy patients and 524 placebo patients). Patients were categorized for mixed features by the number of concurrent manic symptoms at baseline (0, 1 or 2, and ≥3, respectively, as measured by a Young Mania Rating Scale item score ≥1). Efficacy was evaluated by change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to 6 weeks. RESULTS Least-squares mean differences between olanzapine and placebo in the change of MADRS total scores were -3.76 (p=0.002), -3.20 (p<0.001), and -3.44 (p=0.002) for mixed features 0, 1 or 2, and ≥3, respectively. The response rates for olanzapine versus (vs.) placebo were 52.6% vs. 39.8%, 50.3% vs. 40.0%, and 42.2% vs. 33.7% for mixed features 0, 1 or 2, and ≥3, respectively. The remission rates for olanzapine vs. placebo group were 46.1% vs. 34.3%, 39.5% vs. 32.0%, and 34.8% vs. 24.1% for mixed features 0, 1 or 2, and ≥3, respectively. No significant interaction between mixed features and treatment was seen in the MADRS changes or response and remission rates. LIMITATIONS Post hoc analyses of the data from 2 previous randomized clinical studies. CONCLUSIONS Olanzapine monotherapy was shown to be effective in the treatment of bipolar depression irrespective of the presence of concurrent manic symptoms.

Efficacy of olanzapine in the treatment of bipolar mania with mixed features defined by DSM-5

BACKGROUND These analyses compared efficacy of olanzapine in patients with bipolar mania with or without mixed features, as defined in the DSM-5. METHODS Pooled data from 3 placebo-controlled olanzapine studies in patients having bipolar I disorder with manic/mixed episode were analyzed (N=228 olanzapine; N=219 placebo). Patients were categorized for mixed features by number of concurrent depressive symptoms at baseline (0, 1, and 2 [category A; without mixed features], and ≥3 [category B; with mixed features]), as determined by HAM-D17 item score ≥1. Depressive symptoms corresponded to 6 HAM-D17 items in the DSM-5 definition of manic episode with mixed features. Primary efficacy was evaluated by changes in the baseline-to-3-week YMRS total score. RESULTS Patients were categorized into A (N=322; 72.0%) or B (N=125; 28.0%). Mean baseline YMRS total scores were 28.1 in category A and 27.8 in category B. Least-squares mean change of YMRS total scores in categories A and B (olanzapine versus placebo) were -11.78 versus -6.86 and -13.21 versus -4.72, respectively. Patients in the olanzapine- compared with placebo-group experienced a greater decrease in YMRS total score for both categories (p<0.001). An interaction between mixed features and treatment was seen in YMRS change at a 0.3 significance level (p=0.175). LIMITATIONS The results are from post-hoc analyses. CONCLUSIONS Olanzapine was efficacious in the treatment of bipolar I mania, in patients both with and without mixed features, defined by DSM-5; however, greater efficacy was observed in patients with mixed features having more severe depressive symptoms.

Efficacy and safety of olanzapine for treatment of patients with bipolar depression: Japanese subpopulation analysis of a randomized, double-blind, placebo-controlled study

BackgroundThe efficacy and safety of olanzapine monotherapy are evaluated in Japanese patients from a large, global study of bipolar depression.MethodsThis is an analysis of Japanese patients from a 6-week, global (Japan, China, Korea, Taiwan, and the United States), randomized, double-blind, placebo-controlled, Phase 3 study of patients with a depressive episode of bipolar I disorder. The primary outcome was baseline-to-endpoint change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcome measures included the Clinical Global Impressions-Bipolar Version Severity of Illness Scale (CGI-BP), the 17-item Hamilton Depression Rating Scale (HAMD-17) total score, the Young Mania Rating Scale (YMRS) total score, and rates of response (≥50% baseline-to-endpoint reduction in MADRS total score), recovery, and remission.ResultsOf the 156 Japanese patients, 104 had been allocated to olanzapine and 52 to placebo. All results are baseline-to-endpoint change. Compared to placebo, patients in the olanzapine group experienced greater improvement in the primary outcome measure, MADRS total score (−14.9 vs. −10.7; p = .01). They also had greater reductions in the following secondary measures: CGI- BP Depression (−1.41 vs. -0.89; p = .008), CGI-BP Bipolar (−1.31 vs. −0.83; p = .01), HAMD-17 (−11.7 vs. −7.9; p < .01), and YMRS (-0.32 vs. 0.34; p = .03). Differences in rates of response, recovery, and remission were not statistically significant. A greater proportion of olanzapine-treated patients reported treatment- emergent adverse events (87.5% vs. 59.6%; p < .001). Patients treated with olanzapine had greater increases in weight (p < .001) and fasting total cholesterol (p = .008); fasting triglycerides (p = .02), and fasting low-density lipoprotein (p = .01). There was a greater reduction in fasting high-density lipoprotein in olanzapine-treated patients (p = .01). Compared with placebo-group patients, more olanzapine-group patients shifted from borderline to high cholesterol (25.0% vs. 0.0%; p = .007) and had clinically significant weight gain (≥7% body weight) (20.2% vs. 1.9%; p = .001).ConclusionsResults of this analysis support the efficacy and tolerability of olanzapine for the treatment of bipolar depression in Japanese patients. Results in this population were consistent with those seen in the more ethnically diverse parent study. In making treatment decisions for individual patients, clinicians should carefully consider the risks and benefits of olanzapine treatment.Trial RegistrationClinicatrials.gov ID NCT00510146 Olanzapine Treatment of Patients with Bipolar I Disorder

Solanezumab was safe and well-tolerated for Asian patients with mild-to-moderate Alzheimer's disease in a multicenter, randomized, open-label, multi-dose study

Background: Solanezumab is a humanized anti-amyloid-b monoclonal antibody being developed as a passive-immunization treatment to slow the progression of AD. It recognizes a mid-domain epitope of the amyloid-b (Ab) peptide and elicits continuous changes of Ab dynamics. Although multiple doses of solanezumab are safe and well tolerated in non-Japanese, there are no data available in Asians. This is the first study to describe the safety and tolerability of multiple doses of solanezumab in Asian patients with mild-to-moderate AD. Methods: This study was a multicenter, randomized, open-label, parallel study in Japan. Duration was 5 days to 5 weeks in Period I (eligibility), 8 weeks in Period II (treatment), and 16 weeks in Period III (follow-up). Patients were randomized 1:1:1 to 3 solanezumab dose arms: iv infusions of 400 mg once every week (QW group), 400 mg once every four weeks (Q4W group) and 400 mg once every eight weeks (Q8W group). All patients visited every week and blood samples were taken for safety, pharmacokinetics, and pharmacodynamics. Results: Thirty five patients entered the study. Thirty three patients were randomly assigned to treatment, received at least one dose of study drug, and completed the study. Eighteen patients (54.5%) were female, fifteen patients (45.5%) were male, and their ages ranged from 56 to 84 years (mean 1⁄4 70.7). There were no serious adverse events related to solanezumab; although treatment-emergent adverse events (TEAEs) were reported in 8 patients from the Q8W group (66.7%), 5 patients from the Q4W group (50.0%), and 5 patients from the QW group (45.5%). Adverse events reported were mild or moderate except one event. Only one event (pain in extremity) was judged as severe but was not related to the study drug or a study procedure. There were no infusion reactions, MRI evidence of meningoencephalitis, or clinically meaningful laboratory abnormalities. Conclusions: Solanezumab was safe and well-tolerated up to 400 mg once a week in Asian (Japanese) AD patients.

A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in Japanese patients for schizophrenia with acute agitation

No abstract

Safety and efficacy of olanzapine in the long-term treatment of Japanese patients with bipolar I disorder, depression: An integrated analysis

Safety and efficacy of long‐term olanzapine treatment in Japanese patients with bipolar depression were assessed.

Improved outcomes following a switch to olanzapine treatment from risperidone treatment in a 1-year naturalistic study of schizophrenia patients in Japan

Aims:  This study assessed clinical and functional outcomes following a switch from risperidone to olanzapine in a 1‐year naturalistic study of schizophrenia patients in Japan.

An observational study of duloxetine versus SSRI monotherapy in Japanese patients with major depressive disorder: subgroup analyses of treatment effectiveness for pain, depressive symptoms, and quality of life

Objective To examine how clinical and demographic patient baseline characteristics influence effectiveness of duloxetine versus selective serotonin reuptake inhibitor (SSRI) treatment, in real-world Japanese clinical settings of patients with major depressive disorder (MDD) and associated painful physical symptoms (PPS). Methods This was a multicenter, 12-week, prospective, observational study in patients with MDD (Quick Inventory of Depressive Symptomatology ≥16) and at least moderate PPS (Brief Pain Inventory-Short Form [BPI-SF] average pain ≥3). Patients received duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine). Assessments were made by using BPI-SF average pain, 17-item Hamilton Rating Scale for Depression (HAM-D17), EuroQol 5-dimension questionnaire, Social Adaptation Self-Evaluation Scale, Global Assessment of Functioning, and ability to work. Predefined subgroups included the number of previous episodes of depression (0 vs ≥1), baseline BPI-SF average pain score (≤6 vs >6), baseline HAM-D17 total score (≤18 vs >18), baseline HAM-D17 retardation (≤7 vs >7) and anxiety somatic subscale scores (≤6 vs >6), and age (<65 vs ≥65 years). Results Treatment effectiveness was evaluated in 523 patients (duloxetine N=273, SSRIs N=250). Treatment with duloxetine was superior to SSRIs on most outcome measures in patients experiencing their first depressive episode, those with higher baseline PPS levels, and in patients with more severe baseline depression. This was also the case for older patients. In patients with less severe depression, SSRI treatment tended to show more improvements in depression and quality of life measures versus duloxetine treatment. Conclusion These preplanned subgroup analyses of data from a prospective observational study suggest that, for Japanese MDD patients with PPS, duloxetine is more effective than SSRIs in patients with a first episode of MDD, with more severe depression, or more severe PPS.

Assessment of direct analgesic effect of duloxetine for chronic low back pain: post hoc path analysis of double-blind, placebo-controlled studies

Background Comorbid depression and depressive symptoms are common in patients with chronic low back pain (CLBP). Duloxetine is clinically effective in major depressive disorder and several chronic pain states, including CLBP. The objective of this post hoc meta-analysis was to assess direct and indirect analgesic efficacy of duloxetine for patients with CLBP in previous clinical trials. Methods Post hoc path analyses were conducted of 3 randomized, double-blind, clinical studies of patients receiving duloxetine or placebo for CLBP. The primary outcome measure for pain was the Brief Pain Inventory, average pain score. A secondary outcome measure, the Beck Depression Inventory-II, was used for depressive symptoms. The changes in score from baseline to endpoint were determined for each index. Path analyses were employed to calculate the proportion of analgesia that may be attributed to a direct effect of duloxetine on pain. Results A total of 851 patients (400 duloxetine and 451 placebo) were included in this analysis. Duloxetine significantly improved pain scores compared with placebo (p<0.001). It also significantly improved depressive scores compared with placebo (p=0.015). Path analyses showed that 91.1% of the analgesic effect of duloxetine could be attributed to a direct analgesic effect, and 8.9% to its antidepressant effect. Similar results were obtained when data were evaluated at weeks 4 and 7, and when patients were randomized to subgroups based on baseline pain scores, baseline depressive symptoms scores, and gender. Conclusion Duloxetine significantly improved pain in patients with CLBP. Path analyses results suggest that duloxetine produced analgesia mainly through mechanisms directly impacting pain modulation rather than lifting depressive symptoms. This effect was consistent across all subgroups tested.

Remission, response, and relapse rates in patients with acute schizophrenia treated with olanzapine monotherapy or other atypical antipsychotic monotherapy: 12-month prospective observational study

Purpose To compare the rates of antipsychotic response, remission, and relapse in patients with schizophrenia treated with olanzapine or other antipsychotics in usual clinical care in Japan. Patients and methods This analysis of a 12-month, prospective, noninterventional study examined outcomes for 1,089 inpatients and outpatients with schizophrenia who initiated antipsychotic monotherapy. All treatment decisions, including medication choice, were left to the discretion of the treating physician. The rates of treatment response, relapse, and 6-month sustained remission were compared between olanzapine monotherapy (OLZ) and other anti-psychotic monotherapy (OAN), and between OLZ and other atypical antipsychotic monotherapy (OAT). Visit-wise comparisons of treatment response and remission were examined using repeated-measures logistic regressions. Propensity scores were used to control for potential baseline differences between groups. Results Response rates were higher for OLZ patients and relapse rates were consistently lower for OLZ patients, however the differences were not statistically significant. Rates of 6-month sustained remission were significantly higher for OLZ than OAN patients (P=0.032) and for OLZ than OAT patients (P=0.041). An exploratory analysis of OLZ and OAN comparison found outpatients treated with OLZ or OAN had similar sustained remission rates (OLZ: 22.2%, OAN: 22.8%), while inpatients treated with OLZ had significantly higher sustained remission rates than inpatients treated with OAN (OLZ: 17.1%, OAN: 6.6%, odds ratio [95% confidence interval] =3.54 [2.00–6.25]). Conclusion In usual care in Japan, treating the acute symptoms of schizophrenia with olanzapine was not found to be significantly different for response and relapse rates; however, treatment with olanzapine was found to have significantly greater sustained remission rates than treatment with other antipsychotics. In the inpatient setting, where patients tend to be more severe and difficult to manage, olanzapine treatment may lead to higher sustained remission rates than other antipsychotics.