Divalproex extended-release in acute bipolar II depression.
ABSTRACT Divalproex extended-release (divalproex-ER) is effective in acute mania, and limited data suggest divalproex may have efficacy in acute bipolar depression.
A 7-week, open-label trial of divalproex-ER monotherapy or adjunctive therapy was conducted in 28 outpatients (15 female, mean age 36.7+/-9.1, and mean duration of illness 22.1+/-11.1 years) with bipolar II depression (39% with rapid cycling course of illness within the prior year). Divalproex-ER was generally given as a single dose at bedtime, starting at 250mg and increased by 250mg every 4 days to symptom relief or adverse effects. Efficacy was assessed using weekly prospective Montgomery Asberg Depression Rating Scale (MADRS) scores.
Overall, mean divalproex-ER final doses and serum concentrations were 1469mg/day and 80.1microg/mL, respectively. Mean MADRS scores (last observation carried forward) decreased significantly from baseline in patients in the overall group (from 30.1 to 15.2, p<.00001). The overall response rate was 54%. Divalproex-ER therapy was generally well tolerated, with no early discontinuations due to adverse events.
This study is limited by a small sample size and an open-label study design with no placebo control.
Divalproex-ER as monotherapy and adjunctive therapy was well tolerated and yielded an overall response rate of 54% in bipolar II depression. Based on the results of this pilot study, randomized, double-blind, placebo-controlled studies of divalproex-ER in bipolar II depression are warranted.
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ABSTRACT: The efficacy and safety of divalproex sodium extended release (divalproex ER) were evaluated in patients hospitalized for acute mania associated with bipolar I disorder, manic or mixed type (DSM-IV-TR criteria). Following screening and washout of psychotropic medications, 377 patients were randomly assigned in a 1:1 ratio to 21 days of double-blind treatment with divalproex ER (N = 192) or placebo (N = 185). Daily dosage was initiated at 25 mg/kg, increased 500 mg on day 3, and adjusted to serum valproate concentrations of 85 to 125 microg/mL. The Mania Rating Scale (MRS) was used to assess efficacy. Patients remained hospitalized at least 15 days during blinded treatment. The study was conducted from April 2003 to May 2004. Improvement from baseline on the MRS was significantly greater among patients who received divalproex ER compared with placebo at the first on-treatment rating assessment, day 5, and all subsequent ratings through day 21 (p = .013). Furthermore, the proportion of patients achieving at least 50% improvement from baseline in MRS was significantly higher in patients receiving divalproex ER (48%) than in patients receiving placebo (34%) (p = .012). Five of the 11 MRS items improved significantly more in patients receiving divalproex ER than placebo: less need for sleep (p <or= .01), more energetic (p <or= .05), increased activity (p <or= .05), generalized motor hyperactivity (p <or= .05), and racing thoughts (p <or= .001). Side effects associated with divalproex ER included somnolence, dizziness, and gastrointestinal complaints. The results indicate that dival-proex ER is effective and safe for the treatment of mania episodes in bipolar I patients. ClinicalTrials.gov identifier NCT00060905.The Journal of Clinical Psychiatry 10/2006; 67(10):1501-10. · 5.81 Impact Factor
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ABSTRACT: An eleven item clinician-administered Mania Rating Scale (MRS) is introduced, and its reliability, validity and sensitivity are examined. There was a high correlation between the scores of two independent clinicians on both the total score (0.93) and the individual item scores (0.66 to 0.92). The MRS score correlated highly with an independent global rating, and with scores of two other mania rating scales administered concurrently. The score also correlated with the number of days of subsequent stay in hospital. It was able to differentiate statistically patients before and after two weeks of treatment and to distinguish levels of severity based on the global rating.The British Journal of Psychiatry 12/1978; 133:429-35. · 6.61 Impact Factor
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ABSTRACT: More than 40% of patients with major depressive disorder do not achieve remission even after two optimally delivered trials of antidepressant medications. This study compared the effectiveness of lithium versus triiodothyronine (T(3)) augmentation as a third-step treatment for patients with major depressive disorder. A total of 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; N=69) or with T(3) (up to 50 mug/day; N=73) for up to 14 weeks. The primary outcome measure was whether participants achieved remission, which was defined as a score < or =7 on the 17-item Hamilton Depression Rating Scale. After a mean of 9.6 weeks (SD=5.2) of treatment, remission rates were 15.9% with lithium augmentation and 24.7% with T(3) augmentation, although the difference between treatments was not statistically significant. Lithium was more frequently associated with side effects (p=0.045), and more participants in the lithium group left treatment because of side effects (23.2% versus 9.6%; p=0.027). Remission rates with lithium and T(3) augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest and did not differ significantly. The lower side effect burden and ease of use of T(3) augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials.American Journal of Psychiatry 09/2006; 163(9):1519-30; quiz 1665. · 14.72 Impact Factor