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P.2.e.017 Aripiprazole combination with divalproex in patients with acute manic and mixed episode
S458
P.2.e Affective disorders and antidepressants - Bipolar disorders (clinical)
Supported by 1 P20 MH68662. References [1] Bowden CL, Singh V, Thompson, P, Gonzalez JM, Katz MM, Dahl M, Prihoda TJ, Chang X. Development of the Bipolar Inventory of Symptoms Scale. Acta Psychiatrica Scandinavica. 2007; 116:189-194. [2] Gonzalez JM, Bowden CL, Katz MM, Martin M, Thompson PM, Singh V, Prihoda TJ, Dahl, Martha. Development of the Bipolar Inventory of Symptoms Scale: Concurrent validity, discriminant validity and retest reliability International Journal of Methods in Psychiatric Research 17:198-209,2008.
IP.2.e.0171 Aripiprazole combination with divalproex in patients with acute manic and mixed episode
W. Bahk1 ., Y.S. Woo 1 , M.Y. Chunr, D.H. Kim3 , B.H. Yoon4 , 1H. Lee5 , Y.M. Ahn6, S.K. Chung , 1G. Kim8, K.H. Lee 9 . 1 Catholic University of Korea, Department of Psychiatry, Seoul, South-Korea; 2Seoul Veterans Hospital, Department of Psychiatry, Seoul, South-Korea; 3 Hallym University, Department ofPsychiatry, Chuncehon, South-Knrea; 4Naju National Hospital, Department of Psychiatry, Naju, South-Korea; 5 Catholic University of Daegu, Department of Psychiatry, Daegu, SouthKorea; 6 Seoul National University, Department of Psychiatry, Seoul, South-Knrea; 7 Chonbuk National University, Department of Psychiatry, Jeonju, South-Knrea; 8Maryknoll Hospital, Department of Psychiatry, Busan, South-Knrea; 9Dongguk University, Department ofPsychiatry, Gyeongju, South-Korea Objective: The goal of this study was to assess the efficacy and tolerability of aripiprazole in combination with divalproex in patients with acute manic and mixed episode. Method: This study was a large, multicenter, 6-week, openlabel, combination, prospective investigation of Korean patients with an acute manic and mixed episode of bipolar disorder. A total of 100 patients were recruited from 21 hospitals. Aripiprazole 20mg/day was given in combination with flexible dose of divalproex for 7 days. The aripiprazole dose was titrated flexibly (1O-30mg/day) according to the clinical response and tolerability after day 7. The data collected included treatment efficacy using the Young Mania Rating Scale (yMRS), MontgomeryAsberg Depression Rating Scale (MADRS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression-BipolarSeverity-Bipolar version (CGI-BP) at baseline and at week 1, 2, 3, and 6. To evaluate sleep quality, modified form of Leeds Sleep Evaluation Questionnaire (LSEQ) was used. The Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS) were administered at each visit in order to assess tolerability. Results: Sixty-six of the 100 patients (66%) completed the study. Mean aripiprazole dose was 22.1±4.8mg/day and mean divalproex dose was 1000.5±290.6 mg/day. The combination of aripiprazole with divalproex treatment was associated with clinically and statistically significant improvement in the mean scores of the YMRS from 29.7±7.7 at baseline to 9.7±9.4 at 6 weeks (p < 0.0001). The mean scores of MADRS, BPRS, and CGI-BP were also significantly decreased at six weeks (p < 0.001). All the efficacy variables showed significant improvement by week 1. The response rate, on the YMRS, was 73% and remission rate was 70% at week 6. Night time sleep quality measured by modified LSEQ was significantly improved. The combination of aripiprazole and divalproex was well tolerated and adverse events were mostly mild. Twenty four patients (24%) reported
adverse events. No statistically significant changes were seen on the SAS, AIMS, BARS at the study endpoint compared to the baseline. Five adverse events led to withdrawal from the study. The reasons for withdrawal were skin eruption in two patients, akathisia, agitation and insomnia in one patient each. Mean body weight was significantly increased from 65.6±12.3 kg at baseline to 66.7±12.0kg at week 6. Conclusion: The results of this open-label study suggest that aripiprazole combination with divalproex is an effective and safe treatment of the acute manic and mixed phase of bipolar disorder. When compared with the baseline, aripiprazole at mean doses of 22.1±4.8mg/day when combined with divalproex at mean doses of 1000.5±290.6 mg/day showed significant antimanic effects, as measured by the YMRS. Aripiprazole combination with divalproex also significantly decreased depressive symptoms as measured by changes in the MADRS as well as psychotic symptoms as measured by the BPRS. In conclusion, despite the many methodological limitations of this open label study, the results of this multi-centre, 6-week investigation showed that aripiprazole plus divalproex combination treatment for bipolar disorder with acute manic symptoms was safe and effective.
1p.2.e.0181 Thyroid function index and recurrence in patients with bipolar disorders
1M. Kang1o , D.H. Han1, S.Y. Jo0 1 , 1W. Kim1 . lChungAng University Hospital, Neuropsychiatry, Seoul, South-Korea Introduction: Recurrence is an important issue in the progress of bipolar disorders. Thyroid function has been reported to be an important factor in onset or recurrence of mood disorders. Even mild thyroid dysfunction was thought to be associated with either mood swing and the change of cognition in patients with mood disorders. In addition, several lines of evidence supported that changes in T3, free T3, and thyroid stimulating hormone (TSH) can be a risk factor for switch from depression to mania in patients with bipolar I depression patients. Moderate to severe depression and mania are associated with a reduced thyroid stimulating hormone (TSH) response to TSH releasing hormone (TRH). Continued reduction of this response after clinical recovery seems indicative of early relapse. We hypothesized that thyroid hormone abnormalities with bipolar disorders would be associated with hospitalization period and treatment response in outpatient department as measured with non-hospital length of stay (the period from last discharge to re-admission, nHLOS). Methods: We reviewed the medical records of 185 recurrent bipolar patients, aged 27-85, discharged from the Department of Neuropsychiatry, Chung Ang University Hospital, between January 1 1988 and March 312008. Thyroid indices (T3, T4, and TSH) and nHLOS data in every admission were collected from the medical record of patients hospitalized for bipolar disorders. Potential confounds were excluded affect length of hospital stay and frequency of hospitalization; premature hospital discharge (discharge against medical advice or transfer to other hospital), history of psychiatric treatment in other hospital, concomitant medical illness, pregnancy, and alcohol or drug dependence. The patients were classified into two groups; the patients with the history of abnormal thyroid indices level (abnTi) and the patients without the history of abnormal thyroid indices level (nlTi). Results: There was no significant difference in age, education years, onset age, duration of illness, and the history of psychotic
P.2.e Affective disorders and antidepressants - Bipolar disorders (clinical)
Supported by 1 P20 MH68662. References [1] Bowden CL, Singh V, Thompson, P, Gonzalez JM, Katz MM, Dahl M, Prihoda TJ, Chang X. Development of the Bipolar Inventory of Symptoms Scale. Acta Psychiatrica Scandinavica. 2007; 116:189-194. [2] Gonzalez JM, Bowden CL, Katz MM, Martin M, Thompson PM, Singh V, Prihoda TJ, Dahl, Martha. Development of the Bipolar Inventory of Symptoms Scale: Concurrent validity, discriminant validity and retest reliability International Journal of Methods in Psychiatric Research 17:198-209,2008.
IP.2.e.0171 Aripiprazole combination with divalproex in patients with acute manic and mixed episode
W. Bahk1 ., Y.S. Woo 1 , M.Y. Chunr, D.H. Kim3 , B.H. Yoon4 , 1H. Lee5 , Y.M. Ahn6, S.K. Chung , 1G. Kim8, K.H. Lee 9 . 1 Catholic University of Korea, Department of Psychiatry, Seoul, South-Korea; 2Seoul Veterans Hospital, Department of Psychiatry, Seoul, South-Korea; 3 Hallym University, Department ofPsychiatry, Chuncehon, South-Knrea; 4Naju National Hospital, Department of Psychiatry, Naju, South-Korea; 5 Catholic University of Daegu, Department of Psychiatry, Daegu, SouthKorea; 6 Seoul National University, Department of Psychiatry, Seoul, South-Knrea; 7 Chonbuk National University, Department of Psychiatry, Jeonju, South-Knrea; 8Maryknoll Hospital, Department of Psychiatry, Busan, South-Knrea; 9Dongguk University, Department ofPsychiatry, Gyeongju, South-Korea Objective: The goal of this study was to assess the efficacy and tolerability of aripiprazole in combination with divalproex in patients with acute manic and mixed episode. Method: This study was a large, multicenter, 6-week, openlabel, combination, prospective investigation of Korean patients with an acute manic and mixed episode of bipolar disorder. A total of 100 patients were recruited from 21 hospitals. Aripiprazole 20mg/day was given in combination with flexible dose of divalproex for 7 days. The aripiprazole dose was titrated flexibly (1O-30mg/day) according to the clinical response and tolerability after day 7. The data collected included treatment efficacy using the Young Mania Rating Scale (yMRS), MontgomeryAsberg Depression Rating Scale (MADRS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression-BipolarSeverity-Bipolar version (CGI-BP) at baseline and at week 1, 2, 3, and 6. To evaluate sleep quality, modified form of Leeds Sleep Evaluation Questionnaire (LSEQ) was used. The Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS) were administered at each visit in order to assess tolerability. Results: Sixty-six of the 100 patients (66%) completed the study. Mean aripiprazole dose was 22.1±4.8mg/day and mean divalproex dose was 1000.5±290.6 mg/day. The combination of aripiprazole with divalproex treatment was associated with clinically and statistically significant improvement in the mean scores of the YMRS from 29.7±7.7 at baseline to 9.7±9.4 at 6 weeks (p < 0.0001). The mean scores of MADRS, BPRS, and CGI-BP were also significantly decreased at six weeks (p < 0.001). All the efficacy variables showed significant improvement by week 1. The response rate, on the YMRS, was 73% and remission rate was 70% at week 6. Night time sleep quality measured by modified LSEQ was significantly improved. The combination of aripiprazole and divalproex was well tolerated and adverse events were mostly mild. Twenty four patients (24%) reported
adverse events. No statistically significant changes were seen on the SAS, AIMS, BARS at the study endpoint compared to the baseline. Five adverse events led to withdrawal from the study. The reasons for withdrawal were skin eruption in two patients, akathisia, agitation and insomnia in one patient each. Mean body weight was significantly increased from 65.6±12.3 kg at baseline to 66.7±12.0kg at week 6. Conclusion: The results of this open-label study suggest that aripiprazole combination with divalproex is an effective and safe treatment of the acute manic and mixed phase of bipolar disorder. When compared with the baseline, aripiprazole at mean doses of 22.1±4.8mg/day when combined with divalproex at mean doses of 1000.5±290.6 mg/day showed significant antimanic effects, as measured by the YMRS. Aripiprazole combination with divalproex also significantly decreased depressive symptoms as measured by changes in the MADRS as well as psychotic symptoms as measured by the BPRS. In conclusion, despite the many methodological limitations of this open label study, the results of this multi-centre, 6-week investigation showed that aripiprazole plus divalproex combination treatment for bipolar disorder with acute manic symptoms was safe and effective.
1p.2.e.0181 Thyroid function index and recurrence in patients with bipolar disorders
1M. Kang1o , D.H. Han1, S.Y. Jo0 1 , 1W. Kim1 . lChungAng University Hospital, Neuropsychiatry, Seoul, South-Korea Introduction: Recurrence is an important issue in the progress of bipolar disorders. Thyroid function has been reported to be an important factor in onset or recurrence of mood disorders. Even mild thyroid dysfunction was thought to be associated with either mood swing and the change of cognition in patients with mood disorders. In addition, several lines of evidence supported that changes in T3, free T3, and thyroid stimulating hormone (TSH) can be a risk factor for switch from depression to mania in patients with bipolar I depression patients. Moderate to severe depression and mania are associated with a reduced thyroid stimulating hormone (TSH) response to TSH releasing hormone (TRH). Continued reduction of this response after clinical recovery seems indicative of early relapse. We hypothesized that thyroid hormone abnormalities with bipolar disorders would be associated with hospitalization period and treatment response in outpatient department as measured with non-hospital length of stay (the period from last discharge to re-admission, nHLOS). Methods: We reviewed the medical records of 185 recurrent bipolar patients, aged 27-85, discharged from the Department of Neuropsychiatry, Chung Ang University Hospital, between January 1 1988 and March 312008. Thyroid indices (T3, T4, and TSH) and nHLOS data in every admission were collected from the medical record of patients hospitalized for bipolar disorders. Potential confounds were excluded affect length of hospital stay and frequency of hospitalization; premature hospital discharge (discharge against medical advice or transfer to other hospital), history of psychiatric treatment in other hospital, concomitant medical illness, pregnancy, and alcohol or drug dependence. The patients were classified into two groups; the patients with the history of abnormal thyroid indices level (abnTi) and the patients without the history of abnormal thyroid indices level (nlTi). Results: There was no significant difference in age, education years, onset age, duration of illness, and the history of psychotic