Aripiprazole plus divalproex for recently manic or mixed patients with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind maintenance trial.

OBJECTIVES: The goal of this study was to investigate the safety and efficacy in preventing relapse of a mood episode in recently manic or mixed episode patients with bipolar I disorder stabilized with aripiprazole and divalproex combination. METHODS: This randomized, 24-week, double-blind, placebo-controlled multicenter study enrolled patients from 23 centers in Korea. Patients with bipolar I disorder who had manic or mixed episode entered a 6-week open-label stabilization phase. After meeting stabilization criteria, 83 patients were randomly assigned to placebo + divalproex or aripiprazole + divalproex treatment group for the 24-week, double-blind maintenance phase. RESULTS: During the 6-month double-blind treatment, the time to relapse of any mood episode in the aripiprazole group was longer than the placebo group, but the difference did not reach statistical significance (p = 0.098). After controlling for mean divalproex level, the time to depressive episode relapse in the aripiprazole group was longer than those in the placebo group (p = 0.029). Weight gain (≥ 7% increase) occurred in 22.5% aripiprazole group and 18.6% placebo group (p = 0.787). CONCLUSIONS: In this study, relapse of mood episode occurred fewer and later for aripiprazole with divalproex treatment than divalproex monotherapy, but the differences were not statistically significant.

Risperidone in the treatment of mixed state bipolar patients: results from a 24-week, multicenter, open-label study in Korea.

AIMS: The goal of the present study was to evaluate the efficacy of risperidone combined with mood stabilizers for treating bipolar mixed state. METHODS: The present study was a 24-week, open-label, combination, prospective investigation of the efficacy of risperidone in combination with mood stabilizers. Risperidone (1-6 mg/day) was given in combination with mood stabilizers in flexible doses according to clinical response and tolerability for 114 patients in mixed or manic episode. RESULTS: Forty-four patients met our criteria for mixed state bipolar disorder and 70 met the criteria for pure mania. Mean age for the subjects was 39.0 +/- 11.0 years and 55.3% were female. The combination of risperidone with mood stabilizers significantly improved the scores on the Young Mania Rating Scale (YMRS), 17-item Hamilton Rating Scale for Depression (HAMD), 18-item Brief Psychiatric Rating Scale (BPRS), Global Assessment Scale (GAS), and Clinical Global Impression Scale for use in bipolar illness Severity (CGI-BP) at 24 weeks (P < 0.0001). Analysis of the YMRS, BPRS, GAS, and CGI-BP scores showed significant improvement in both the manic and mixed groups. The rate of response in YMRS scores was 84.2% (n = 96) and the rate of YMRS remission was 77.2% (n = 88) at week 24 in the total population. Seventy-four patients met both YMRS < or = 12 and HAMD < or = 7 at week 24 (64.9%). Risperidone was well tolerated, and adverse events were mostly mild. CONCLUSION: The combination of risperidone with mood stabilizers was an effective and safe treatment for manic symptoms and coexisting depressive symptoms of bipolar disorder.

A micro opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients.

RATIONALE: Previous studies have demonstrated an association between genetic polymorphisms of the mu opioid receptor gene (OPRM1) and response to naltrexone treatment. The Asp40 variant genotype previously shown to be associated with naltrexone treatment response is known to be relatively common among Koreans. OBJECTIVES: This study was conducted to prospectively investigate the relationship between genotype and response to open-label naltrexone treatment in Korean alcohol-dependent subjects. MATERIALS AND METHODS: Sixty-three alcohol-dependent subjects were prescribed naltrexone for 12 weeks in combination with cognitive behavioral therapy. Thirty-two subjects were adherent, taking the medication at least 80% of the treatment days [16 Asn40 (A/A) patients and 16 Asp40 variant (A/G or G/G) patients]. RESULTS: Subjects adherent to naltrexone treatment with one or two copies of the Asp40 allele took a significantly longer time than the Asn40 group to relapse (p=0.014). Although not significant, the Asn40 group treated with naltrexone had a 10.6 times greater relapse rate than the Asp40 variant group. There was no significant difference between the Asn40 group and the Asp40 variant group treated with naltrexone in rates of abstinence. CONCLUSIONS: These results demonstrating a higher therapeutic effect of naltrexone in Korean alcohol-dependent individuals with the Asp40 variant genotype than the Asn40 genotype are consistent with previous study results in individuals of European descent. This is the first study to examine the pharmacogenetics treatment response to naltrexone in non-European subjects.

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.