Juruena M F, Ottoni G L, Machado-Vieira R, Carneiro R M, Weingarthner N, Marquardt A R, Fleig S S, Broilo L, Busnello E A
King's College London, Institute of Psychiatry, Section of Neurobiology of Mood Disorders, London, UK.
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):94-9. doi: 10.1016/j.pnpbp.2008.10.012. Epub 2008 Oct 31.
Bipolar affective disorders often require adjunctive therapy to treat persistent symptoms. In order to evaluate bipolar symptoms inadequately responsive to lithium, we have compared the effects of two structurally related compounds carbamazepine (CBZ) and oxcarbazepine (OXC). We evaluated the efficacy and safety of CBZ and OXC administration in residual symptoms as an adjunctive therapy in Bipolar I (BP I) and Bipolar II (BP II) patients while on lithium maintenance treatment. We selected from 153 bipolar patients in treatment those fulfilling Research Diagnostic Criteria for mania or hypomania, according to the SADS-L and conducted in 52 bipolar patients (27 BP I, 25 BP II) a double-blind, randomized, parallel-group, single centre, clinical trial. Bipolar I and II outpatients, were randomly assigned on a 1:1 ratio to OXC (n=26) or CBZ (n=26) for an 8-week period as add-on treatment to the existing lithium regimen. Outcome measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale 21 items (HDRS-21) and Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression severity (CGI-S) and improvement illness (CGI-I). These scales were administered at baseline and at the end of weeks 2, 4 and 8. All the fifty-two patients completed the trial. Overall, females were 35 (65%) and mean (S.D.) age was 39.4 (11.9) years; final doses at the end of week 8 in OXC group was 637.7 (210) mg/day and in the CBZ group 673.5 (179) mg/day; lithium plasma levels were 0.73 (0.25) meq/l and 0.71 (0.28) meq/l, respectively. Both OXC and CBZ were effective in reducing bipolar scores from baseline to endpoint (p<0.01). OXC was more effective than CBZ at weeks 4 and 8 on all 5 outcome measures. OXC resulted in greater significant mean reductions in YMRS, HDRS-21, MADRS, CGI-S and CGI-I scores from baseline to week 4 (p<0.05) and from baseline to week 8 (p<0.001), except YMRS (p<0.01). OXC appeared to be significantly more effective and with better tolerability than CBZ as add-on strategy treatment in BP I and BP II patients. This pilot, randomized clinical trial, suggests the potential usefulness of OXC as adjunctive therapy to lithium both in acute and long-term treatment of bipolar disorder. However, further adequately placebo-controlled trials are needed to expand these findings.
双相情感障碍通常需要辅助治疗来处理持续存在的症状。为了评估对锂盐反应欠佳的双相症状，我们比较了两种结构相关化合物卡马西平（CBZ）和奥卡西平（OXC）的效果。我们评估了在双相I型（BP I）和双相II型（BP II）患者接受锂盐维持治疗时，CBZ和OXC作为辅助治疗对残留症状的疗效和安全性。我们从153例接受治疗的双相患者中，根据情感障碍和精神分裂症检查提纲（SADS-L）选择出符合躁狂或轻躁狂研究诊断标准的患者，并对52例双相患者（27例BP I，25例BP II）进行了一项双盲、随机、平行组、单中心临床试验。双相I型和II型门诊患者按1:1比例随机分配至OXC组（n = 26）或CBZ组（n = 26），为期8周，作为现有锂盐治疗方案的附加治疗。疗效指标包括杨氏躁狂评定量表（YMRS）、汉密尔顿抑郁评定量表21项（HDRS - 21）、蒙哥马利-阿斯伯格抑郁评定量表（MADRS）、临床总体印象严重程度（CGI - S）和病情改善情况（CGI - I）。这些量表在基线时以及第2、4和8周结束时进行评定。所有52例患者均完成了试验。总体而言，女性有35例（65%），平均（标准差）年龄为39.4（11.9）岁；第8周结束时OXC组的最终剂量为637.7（210）mg/天，CBZ组为673.5（179）mg/天；锂盐血浆水平分别为0.73（0.25）meq/l和0.71（0.28）meq/l。OXC和CBZ均能有效降低从基线到终点的双相评分（p < 0.01）。在第4周和第8周时，在所有5项疗效指标上OXC比CBZ更有效。从基线到第4周（p < 0.05）以及从基线到第8周（p < 0.001），OXC导致YMRS、HDRS - 21、MADRS、CGI - S和CGI - I评分从基线有更大的显著平均降低，YMRS除外（p < 0.01）。在BP I和BP II患者中，作为附加治疗策略，OXC似乎比CBZ显著更有效且耐受性更好。这项初步的随机临床试验表明，OXC作为锂盐的辅助治疗在双相情感障碍的急性和长期治疗中可能有用。然而，需要进一步进行充分的安慰剂对照试验来扩展这些发现。
