[Show abstract][Hide abstract] ABSTRACT: IntroductionThis article aims to assess the efficacy and safety of atomoxetine in Korean adults with attention-deficit hyperactivity disorder (ADHD).Methods
This post hoc double-blind, placebo-controlled study of atomoxetine (40–120 mg/day) over 10 weeks in adults with ADHD at 45 Japanese, Korean, and Taiwanese study sites focused on patient data from Korea (atomoxetine, n = 37; placebo, n = 37). Primary efficacy outcome was change in baseline-to-endpoint Conners' Adult ADHD Rating Scale-Investigator-rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptoms score. Secondary efficacy outcomes included changes in Adult ADHD Quality of Life (AAQoL) total, Behavior Rating Inventory of Executive Function-Adult Version Self-Report (BRIEF-A:Self-Report), and Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale scores.ResultsAtomoxetine-treated patients demonstrated a mean 18.9-point reduction in CAARS-Inv:SV total ADHD Symptoms score, compared with the 7.45-point reduction in placebo-treated patients (P ≤ 0.01). Significantly greater improvement was found for atomoxetine versus placebo in CGI-ADHD-S (P ≤ 0.01), BRIEF-A:Self-Report global executive composite (P ≤ 0.05), and metacognition index (P ≤ 0.01) executive function scores. Nausea, decreased appetite, and dry mouth were reported with significantly greater frequency by atomoxetine-treated patients, and only one placebo-treated patient discontinued because of adverse event. A 2.1-kg reduction in weight and a 7.5-beat/minute increase in pulse rate were observed in atomoxetine-treated patients.DiscussionThese data support a significant benefit of 80- to 120-mg once daily atomoxetine versus placebo for treatment of ADHD in adult Korean patients. A high placebo response rate was observed in this adult Korean sample; a higher discontinuation rate was also observed in atomoxetine-treated patients. These observations warrant further investigation.
No preview · Article · Nov 2014 · Asia-Pacific Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Safety and efficacy of long-term olanzapine treatment in Japanese patients with bipolar depression were assessed.
An integrated analysis of data from 2 studies was performed in olanzapine-treated patients (N=165) with bipolar depression. Study 1 was a 6-week, double-blind, global study. Patients were randomly assigned to olanzapine or placebo followed by 18 weeks of open-label treatment. Study 2 was an open-label extension of Study 1 involving only Japanese patients. Patients assigned to Pre-olanzapine and Pre-placebo in Study 1 were treated for 24 weeks (total olanzapine exposure 42 or 48 weeks) and newly recruited patients (New-olanzapine) were treated for 48 weeks. Safety outcomes included treatment-emergent adverse events and changes in metabolic parameters. Efficacy outcome was assessed with Montgomery-Åsberg Depression Rating Scale score.
Forty-three percent of patients completed the 42- or 48-week olanzapine treatment period. The most common treatment-emergent adverse event was weight increase (47.9%). Significant increases were seen in weight (3.5 kg), and in fasting glucose (3.5 mg/dL), fasting total cholesterol (8.1 mg/dL), and fasting triglycerides (35.1 mg/dL). Remission rates (Montgomery-Åsberg Depression Rating Scale total score ≤12 at any time) were 79.8% for the Pre-olanzapine group, 90.2% for the Pre-placebo group, and 85.0% for the New-olanzapine group. No patents developed mania during treatment.
Long-term use of olanzapine in a Japanese population with bipolar depression is associated with increases in weight and fasting metabolic measures, and also with improved depressive symptoms with avoidance of mania. Clinicians must carefully consider the benefits and risks of long-term therapy with olanzapine.
No preview · Article · Jan 2014 · Psychiatry and Clinical Neurosciences
[Show abstract][Hide abstract] ABSTRACT: The primary aim of this study was to evaluate the long-term safety/tolerability of atomoxetine in Japanese adults with attention deficit hyperactivity disorder (ADHD).
This 48-week, open-label extension study involved participants with ADHD who completed a 10-week randomized controlled trial of atomoxetine. Participants received atomoxetine 40 mg/day, followed by step-wise titration to a maximum of 120 mg/day. The primary outcome was safety/tolerability. Secondary outcomes were symptoms of ADHD (Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version 18-item total score), quality of life (Adult Attention-Deficit/Hyperactivity Disorder Quality of Life scale), and executive function (Behavior Rating Inventory of Executive Function-Adult Version: Self-report).
Of the 39.5% of participants overall who discontinued the study, 15.9% (37/233) of participants discontinued because of adverse events (AEs), primarily nausea (4.3%; 10/233). Overall, 93.6% (218/233) of participants experienced treatment-emergent AEs (TEAEs), most commonly nausea (56.2%; 131/233), nasopharyngitis (25.3%; 59/233), thirst (19.3%; 45/233), headache (17.2%; 40/233), and decreased appetite (16.3%; 38/233). Most TEAEs (70.8%; 165/233) were mild in intensity. Overall, 79.8% (186/233) of participants experienced ≥1 adverse drug reaction, primarily nausea (55.4%; 129/233). Five participants experienced serious AEs during the open-label extension; none was related/possibly related to treatment. There were statistically significant increases in vital signs and decreases in body weight that were not considered clinically significant. Symptoms of ADHD, quality of life, and executive function were significantly improved from baseline to endpoint (P < 0.05).
Despite discontinuations due to the long-term, open-label design, AE related discontinuations were modest, suggesting that atomoxetine has acceptable long-term safety and tolerability in Japanese adults with ADHD. Symptoms of ADHD improved and remained improved throughout the study.
No preview · Article · Dec 2013 · Asia-Pacific Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Objective: The efficacy and safety of atomoxetine was assessed in adult ADHD patients from Japan, Korea, and Taiwan in this first placebo-controlled Asian clinical study in adults of an ADHD medication. Method: Atomoxetine was compared with placebo (195 atomoxetine, 196 placebo) over 10 weeks. The change from baseline to endpoint and changes over time in the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version total score (CAARS-Inv: SV total score) were assessed along with changes in quality of life (QoL) and executive function. Results: Atomoxetine treatment resulted in a mean reduction of -14.3 (placebo, -8.8) in CAARS-Inv: SV total score and a steady increase of between-group differences from Week 2. Improvements in QoL and executive functioning were also observed. Treatment-emergent adverse events leading to discontinuation were infrequent (atomoxetine: 5.2%, placebo: 1.5%). Conclusion: Atomoxetine was tolerable and effective in improving QoL and executive function as well as ameliorating core ADHD symptoms in adult Asian patients. (J. of Att. Dis. 2013; XX(X) XX-XX).
No preview · Article · Nov 2013 · Journal of Attention Disorders
[Show abstract][Hide abstract] ABSTRACT: The efficacy and safety of olanzapine monotherapy are evaluated in Japanese patients from a large, global study of bipolar depression.
This 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.
Of 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).
Results 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.
Clinicatrials.gov ID NCT00510146 Olanzapine Treatment of Patients with Bipolar I Disorder
[Show abstract][Hide abstract] ABSTRACT: Olanzapine rapid-acting intramuscular (IM) injection is an atypical antipsychotic drug already used overseas and recently approved in Japan. The objective of this study was to confirm the efficacy of rapid-acting IM olanzapine 10 mg was greater than IM placebo in patients with exacerbation of schizophrenia with acute psychotic agitation by comparing changes from baseline to 2 hours after the first IM injection, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) total score.
We conducted a placebo-controlled, randomized, double-blind, parallel-group study in Japanese patients diagnosed with schizophrenia according to the diagnostic criteria specified in the DSM-IV-TR. Patients were randomized to 2 treatment groups: IM olanzapine (10 mg) or IM placebo. The primary efficacy outcome was the change in PANSS-EC from baseline to 2 hours after the first IM injection. Treatment groups were compared with an analysis of variance model which included treatment and site as factors. During the 24-hour treatment period, safety was assessed by clinical examination and laboratory investigations, electrocardiograms, extrapyramidal symptoms scales, and recording spontaneously reported adverse events.
Of the 91 randomized patients, 90 patients (45 IM olanzapine-group; 45 IM placebo-group) were in the full analysis set. The mean change of PANSS-EC total score from baseline to 2 hours after the first IM injection (mean±standard deviation) was −9.2±4.5 for the IM olanzapine group and −2.8±5.6 for the IM placebo group. The difference between treatment groups was statistically significant (p<.001). There were no deaths, serious adverse events, treatment-emergent adverse events (TEAEs) leading to discontinuation, severe TEAEs, or instances of oversedation in this study. There were no statistically significant differences between treatment groups in the proportion of patients with potentially clinically significant changes in laboratory tests, vital signs (blood pressure and pulse rate), electrocardiograms, and treatment-emergent extrapyramidal symptoms.
The efficacy of IM olanzapine 10 mg in patients with exacerbation of schizophrenia with acute psychotic agitation was greater than IM placebo in the primary efficacy measure, PANSS-EC. Intramuscular olanzapine 10 mg was shown to be generally safe and tolerable, and could be a new option for treatment of schizophrenia in Japan.
[Show abstract][Hide abstract] ABSTRACT: The primary objective of this study was to assess the overall safety and tolerability of atomoxetine in Korean, Chinese, and Taiwanese adults with attention-deficit/hyperactivity disorder (ADHD).
A total of 44 patients aged ≥18 years who met the Conners' Adult ADHD Diagnostic Interview for DSM-IV diagnostic criteria for ADHD were enrolled from China, Korea, and Taiwan. In this open-label, dose-escalation study, patients received atomoxetine orally once daily over a period of eight weeks, starting at 40 mg/day (one week) up to a maximum dosage of 120 mg/day. Tolerability was evaluated by rate of discontinuation due to adverse events. Safety was assessed by recording all adverse events, laboratory tests, vital signs, and electrocardiograms. ADHD symptoms were evaluated by the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) for efficacy assessment.
Thirty-four patients (77.3%) completed the study. Atomoxetine was well tolerated with a discontinuation rate of 2.3% (1/44) due to adverse events. The most commonly reported adverse events were nausea, dizziness, and somnolence. The mean change from baseline to endpoint in CAARS-Inv:SV total ADHD symptom score was -12.5 (P < 0.001). A significant reduction in the CAARS-Inv:SV subscales (inattentive, hyperactive/impulsive, and ADHD index score, P < 0.001) was observed.
This is the first atomoxetine clinical trial in adult patients with ADHD in China, Korea, and Taiwan. Atomoxetine was well tolerated in doses of up to 120 mg/day with no unknown safety concerns.
No preview · Article · Jul 2012 · Asia-Pacific Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Antipsychotic monotherapy is often recommended over antipsychotic polypharmacy because of fewer adverse events, reduced treatment complexity, and lower medication cost. This study compared the rate and the duration of antipsychotic monotherapy following initiation of olanzapine or risperidone in the treatment of outpatients with schizophrenia in Japan.
Outpatients diagnosed with schizophrenia in the Japan Medical Data Center database were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, diagnosis codes. Patients were between 20 and 65 years old, initiated on olanzapine or risperidone therapy between August 2003 and July 2008, and continuously enrolled during the 6 months prior to and the 12 months following the initiation date. Antipsychotic polypharmacy was defined as concurrent use of two or more antipsychotics. The probability of monotherapy during the 12-month follow-up period was assessed using a propensity score-adjusted generalized estimating equation model. Duration of monotherapy was contrasted using a propensity score-adjusted bootstrapping model.
After applying all inclusion and exclusion criteria, the final analytic sample consisted of 332 olanzapine- and 496 risperidone-treated outpatients. At treatment initiation, 61.5% of the olanzapine-treated patients and 45.6% of the risperidone-treated patients received antipsychotic monotherapy (P < 0.001). After correcting for background differences, monotherapy was more common among olanzapine-treated patients (P = 0.001). In addition, olanzapine was used as monotherapy for a longer duration (P = 0.006).
Consistent with prior global research, this retrospective naturalistic study of schizophrenia outpatients in Japan found that olanzapine is more likely to be used as monotherapy and to be used as monotherapy for a longer duration than risperidone.
Full-text · Article · Jun 2012 · Neuropsychiatric Disease and Treatment
[Show abstract][Hide abstract] ABSTRACT: 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.
We used data from a large 1-year prospective, multicenter, observational non-interventional study of individuals who were initiated on olanzapine for the treatment of schizophrenia in Japan. Current analyses focused on patients who were switched at study entry from risperidone to olanzapine (n = 258). Repeated measures analysis was employed to assess outcomes on validated measures.
At study entry, 45% were inpatients and 55% outpatients. Participants were in their early 40s with mean illness duration of 14 years. Approximately half were male. Most were switched from risperidone to olanzapine due to poor medication efficacy (67.8%) rather than medication intolerability (29.1%). Most patients (67.8%) completed the 1-year study. Patients experienced clinically and statistically significant (P < 0.05) improvements in global symptom severity, positive, negative, depressive, and cognitive symptoms, health-related quality of life, and paid work rates. Most patients (59.2%) demonstrated treatment response to olanzapine and 43.4% experienced symptom remission. Mean weight gain was 2.19 kg, with one-third of patients (33.3%) experiencing clinically significant weight gain (≥7%).
In this 1-year naturalistic study, inpatients and outpatients who were switched from risperidone to olanzapine experienced clinically and statistically significant improvements in their clinical and functional outcomes. One-third of all patients experienced clinically significant weight gain. Current findings highlight the favorable benefit-to-risk profile of switching to olanzapine therapy following treatment failure on risperidone among patients with schizophrenia in Japan.
Full-text · Article · Jun 2012 · Psychiatry and Clinical Neurosciences
[Show abstract][Hide abstract] ABSTRACT: To assess the safety and efficacy of 18-week olanzapine monotherapy in Japanese patients with bipolar mania, following a 6-week, placebo- and haloperidol-controlled double-blind study (acute study). For those who discontinued the acute study due to lack of efficacy, safety and efficacy was assessed with a combination therapy of olanzapine and a mood stabilizer.
In this open-label, multicenter extension study, patients who completed the acute study received olanzapine (5-20 mg/day) as monotherapy, and patients who discontinued the acute study due to lack of efficacy with greater Young Mania Rating Scale (YMRS) total score than the acute study baseline, received olanzapine in combination with one of three mood stabilizers: lithium, carbamazepine, or valproate. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, weight, and extrapyramidal symptoms (EPSs). Efficacy measures included YMRS total score, and response and remission rates of manic symptoms.
There were no deaths or serious adverse events considered potentially related to olanzapine in the monotherapy group (N = 100) or the combination-therapy group (N = 39). TEAEs occurred in 59.0% and 79.5% of patients in the monotherapy and combination-therapy groups, respectively, and their severities were mostly mild or moderate. Regarding the efficacy measures, in the monotherapy group, mean YMRS change from extension study baseline to endpoint was -3.0, and the response and remission rates at endpoint were 97.0% and 93.0%, respectively. In the combination-therapy group, mean YMRS change from extension-study baseline was -19.8; response and remission rates increased from the extension-study baseline (both 0.0%) to 64.1% and 61.5% respectively by endpoint.
Olanzapine was generally well tolerated during the 18-week extension period in Japanese patients with bipolar mania. Results of both groups were also generally consistent with US and European studies. Monitoring of metabolic parameters is recommended.
No preview · Article · Feb 2012 · Current Medical Research and Opinion
[Show abstract][Hide abstract] ABSTRACT: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.
In a large (N = 1850) prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and χ(2) tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.
Patients treated with olanzapine monotherapy (43.2%) differed from those treated with antipsychotic polypharmacy (56.8%) on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical).
Consistent with prior research in Japan, antipsychotic polypharmacy appears to be common in the treatment of schizophrenia. Patients treated with monotherapy could be differentiated from those treated with antipsychotic polypharmacy based on a specific set of demographic and baseline clinical characteristics.
Preview · Article · Jan 2012 · ClinicoEconomics and Outcomes Research
[Show abstract][Hide abstract] ABSTRACT: Treatment continuation is considered an important measure of antipsychotic effectiveness in schizophrenia, reflecting the medication's efficacy, safety, and tolerability from both patients' and clinicians' perspectives. This study identified characteristics of patients with schizophrenia who continue olanzapine therapy for a 1-year period in Japan.
In a large (N = 1850), prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Baseline characteristics were compared using t-tests and chi-square tests. Stepwise logistic regression was used to identify independent baseline predictors of treatment continuation.
Most patients (68.2%) continued with olanzapine therapy for the full 1-year study period, with an average duration of 265.5 ± 119.4 days. At baseline, patients who continued were significantly more likely to be male, older, and inpatients; have longer illness duration, higher negative and cognitive symptoms, better health-related quality of life, and prior anticholinergic use. Continuers were significantly less likely to engage in social activities, live independently, work for pay, or have prior antidepressant use. Continuers showed significantly greater early (3-month) improvement in global symptom severity. Logistic regression found that continuation was significantly predicted by longer illness duration, lower positive symptoms, higher negative symptoms, and better health-related quality of life.
In this large naturalistic study in Japan, most patients with schizophrenia stayed on olanzapine therapy for the full 1-year study period. Treatment completion with olanzapine was independently predicted by longer illness duration, lower positive symptoms, higher negative symptoms, and better health-related quality of life.
Preview · Article · Dec 2011 · Patient Preference and Adherence
[Show abstract][Hide abstract] ABSTRACT: No current data were available regarding the efficacy and safety of olanzapine in Japanese patients with bipolar I disorder with a current manic/mixed episode.
Patients received blindly olanzapine (5-20 mg/day; N=105), haloperidol (2.5-10 mg/day; N=20), or placebo (N=99) for 3 weeks. For the following 3 weeks, the olanzapine and haloperidol groups continued their treatment, while the placebo group switched blindly to olanzapine. The primary efficacy measure was the mean change in Young Mania Rating Scale (YMRS) total score; secondary efficacy measures included bipolar disorder remission rate and switch-to depression. Safety measures included treatment-emergent adverse events (TEAEs), weight and extrapyramidal symptoms (EPSs).
YMRS total score significantly decreased in the olanzapine group compared with the placebo group (-5.62 [95% CI: -8.87, -2.37], p<0.001) after 3 weeks. Compared with haloperidol, olanzapine was not markedly different in improving overall bipolar symptomatology, and fewer olanzapine-treated patients switched to symptomatic depression (2.4% vs 16.7%, p=0.014). Overall incidences of TEAEs were not significantly different among the groups, and EPSs in olanzapine group were less severe than in the haloperidol group.
The small haloperidol sample size limited the conclusions that can be drawn from the statistical comparisons between the active treatments.
This was the first study to evaluate an atypical antipsychotic in Japanese patients with manic bipolar I disorder. Consistent with previous non-Japanese studies, olanzapine was generally well-tolerated and superior to placebo in improving the severity of manic symptoms. Compared to haloperidol, fewer olanzapine-treated patients switched to symptomatic depression, and EPSs were less severe.
No preview · Article · Nov 2011 · Journal of Affective Disorders
[Show abstract][Hide abstract] ABSTRACT: The main purpose of this first atomoxetine study in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8-week treatment regimen.
This was an open-label, dose escalation study conducted in 45 Japanese patients aged at least 18 years with DSM-IV-defined ADHD. Patients received atomoxetine orally for 8 weeks. Atomoxetine administration was started at 40 mg/day (7 days), and subsequently increased to a maximum dose of 120 mg/day. Tolerability was assessed by discontinuation rate due to adverse events. Adverse events, laboratory tests, vital signs and electrocardiograms were collected. In addition, ADHD symptoms were assessed by using the Japanese version of the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) scores.
Thirty-nine patients completed the study period. Atomoxetine was well tolerated with a 6.7% (3/45) discontinuation rate due to nausea, malaise and anorexia. The most commonly reported adverse events were nausea, nasopharyngitis and headache; there were no unexpected safety concerns. No deaths or serious adverse events were reported. Mean CAARS-Inv:SV-J total ADHD symptom scores decreased in a time-dependent manner; the mean change from baseline to endpoint was -15.0 (P<0.001).
This study showed that atomoxetine was well tolerated in these patients and suggested that atomoxetine at a maximum dose of 120 mg/day would be safe in Japanese ADHD patients.
Full-text · Article · Feb 2011 · Psychiatry and Clinical Neurosciences