Comparison of two anticonvulsants in a randomized, single-blind treatment of hypomanic symptoms in patients with bipolar disorder
ABSTRACT Oxcarbazepine was compared to divalproex to assess clinical effectiveness of a proven agent, divalproex, against a newer, less studied agent, oxcarbazepine, in the treatment of hypomania.
Thirty patients with bipolar disorder, currently hypomanic, were randomized to receive oxcarbazepine or divalproex as add-on or monotherapy for 8 weeks. A rater blind to treatment assignment performed all symptom ratings. Hypomania and depression were rated using the Young Mania Rating Scale (YMRS) and the Inventory of Depressive Symptoms-Clinician Version (IDS-C). Random regression models were used to assess clinical symptom scores.
There were no significant differences of YMRS or IDS-C scores between groups. Mean YMRS scores at baseline were 22.07+/-5.86 and 20.53+/-6.02 for the oxcarbazepine and the divalproex groups, respectively. Mean percent reduction from baseline to week 8 for the YMRS was 63.8% and 79.0% for oxcarbazepine and divalproex groups, respectively. Mean percent reduction from baseline to week 8 for the IDS-C was 48.7% versus 19.7% for oxcarbazepine and divalproex groups, respectively. Significant antimanic efficacy was noted for each medication. Both medications were generally well tolerated.
In this pilot study, oxcarbazepine was as effective as divalproex in the treatment of hypomania. Further controlled trials are warranted.
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ABSTRACT: Oxcarbazepine, a keto derivative of the 'mood stabiliser' carbamazepine, may have efficacy in the treatment of acute episodes of bipolar disorder. Potentially, it may offer pharmacokinetic advantages over carbamazepine. To review the efficacy and acceptability of oxcarbazepine compared to placebo and other agents in the treatment of acute bipolar episodes including mania, mixed episodes and depression. Electronic databases were searched up to 2 September 2011. Specialist journals and conference proceedings were handsearched. Authors, experts in the field and pharmaceutical companies were contacted requesting information on published and unpublished trials. Randomised controlled trials (RCTs) which compared oxcarbazepine with placebo or alternative agents, where the stated intent of intervention was the acute treatment of bipolar affective disorder were sought. Participants with bipolar disorder of either sex and of all ages were included. Data were extracted from the original reports individually by two review authors. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI). Continuous data were analysed using standardised mean differences (with 95% CI). Seven studies were included in the analysis (368 participants in total). All were on mania, hypomania, mixed episodes or rapid-cycling disorder. Overall, their methodological quality was relatively low.There was no difference in the primary outcome analysis - a fall of 50% or more on the Young Mania Rating Scale (YMRS) - between oxcarbazepine and placebo (N=1, n=110, OR =2.10, 95% CI 0.94 to 4.73) in one study, conducted in children; no studies were available in adult participants.In comparison with other mood stabilisers, there was no difference between oxcarbazepine and valproate as an antimanic agent using the primary outcome (50% or more fall in YMRS, OR=0.44, 95% CI 0.10 to 1.97, 1 study, n=60, P=0.273) or the secondary outcome measure (differences in YMRS between the two groups, SMD=0.18, 95% CI -0.24 to 0.59, 2 studies, n=90, P=0.40). No primary or secondary efficacy outcome measures were found comparing oxcarbazepine with lithium monotherapy.As an adjunctive treatment to lithium, oxcarbazepine reduced depression rating scale scores more than carbamazepine in a group of manic participants on the Montgomery-Åsberg Depression Rating Scale (MADRS) (SMD=- 1.12, 95% CI -1.71 to -0.53, 1 study, n=52, P=0.0002) and on the Hamilton Depression Rating Scale (HDRS) (SMD=- 0.77, 95% CI -1.35 to -0.20, 1 study, n=52, P=0.008).There was a higher incidence of adverse effects, particularly neuropsychiatric, in participants randomised to oxcarbazepine compared to those on placebo (1 study, n=115, 17% to 39% of participants on oxcarbazepine had at least one such event compared to 7% to 10% on placebo).There was no difference in adverse events rates between oxcarbazepine and other mood stabilisers or haloperidol. Currently, there are insufficient trials of adequate methodological quality on oxcarbazepine in the acute treatment of bipolar disorder to inform us on its efficacy and acceptability. Studies predominantly examine the treatment of mania: there are data from subgroup analysis on mixed affective, hypomania and rapid-cycling states.From the few studies included in this review, oxcarbazepine did not differ in efficacy compared to placebo in children and adolescents. It did not differ from other active agents in adults. It may have a poorer tolerability profile compared to placebo. No data were found on outcomes relevant to patients and clinicians, such as length of hospital admission. There is a need for adequately powered randomised controlled trials of good methodological quality to inform us of the therapeutic potential of oxcarbazepine across the spectrum of acute episodes in bipolar disorder.Cochrane database of systematic reviews (Online) 01/2011; DOI:10.1002/14651858.CD004857.pub2 · 5.94 Impact Factor
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ABSTRACT: Type-1 diabetes mellitus (DM) is a lifelong serious condition which often renders the application of standard treatment options for patients' comorbid conditions, such as bipolar disorder I, risky - especially for acute manic episodes. We present such a case whereby the application of standard anti-manic treatments would have jeopardized a patient whose physical condition was already compromised by DM. We report the case of a 55-year-old female with a history of type-1 DM since the age of 11, and severe ocular and renal vascular complications thereof. While on the waiting list for pancreatic islet cell transplantation, she developed a manic episode that proved recalcitrant to a treatment with gabapentin, lorazepam and quetiapine. Moreover, her mental state affected adversely her already compromised glycemic control, requiring her psychiatric hospitalization. Her psychotropic medication was almost discontinued and replaced by oxcarbazepine (OXC) up to 1800 mg/day for 10 days. The patient's mental state improved steadily and on discharge, 3 weeks later, she showed an impressive improvement rate of over 70% on the YMRS. Moreover, she remains normothymic 6 months after discharge, with OXC at 1200 mg/day. Standard prescribing guidelines for acute mania recommend a combination of an antipsychotic with lithium or, alternatively, a combination of an antipsychotic with valproate or carbamazepine. However, in our case, administration of lithium was at least relatively contra-indicated because of patient's already compromised renal function. Furthermore, antipsychotics increase glucose levels and thus were also relatively contra-indicated. Moreover, the imminent post-transplantation immunosuppressant treatment with immuno-modulating medicines also contra-indicated both valproate and carbamazepine. Despite the severe methodological limitations of case reports in general, the present one suggests that OXC as monotherapy might be both safe and efficacious in the treatment of acute mania in patients with early-onset type-1 DM, whose already compromised physical condition constitutes an absolute or relative contra-indication for the administration of standard treatments, though there are no, as yet, randomized clinical trials attesting to its efficacy unambiguously.Annals of General Psychiatry 02/2007; 6:25. DOI:10.1186/1744-859X-6-25 · 1.53 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.