A double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania.
A double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania.
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DOI：
10.4088/jcp.v69n0806
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发表时间：
2008-08
期刊：
影响因子：
--
通讯作者：
Kapczinski F
中科院分区：
文献类型：
--
作者：
Machado-Vieira R;Soares JC;Lara DR;Luckenbaugh DA;Busnello JV;Marca G;Cunha A;Souza DO;Zarate CA Jr;Kapczinski F
双相情感障碍（BD）的治疗方法仍然远远不够，需要在广泛的患者中提高有效性，安全性和耐受性的新选择。初步数据表明，嘌呤能系统功能障碍在情绪障碍中的作用。本研究旨在评价嘌呤能药物别嘌呤醇和双嘧达莫联合锂治疗双相躁狂症的疗效和耐受性。一项随机、安慰剂对照、双盲研究在成年住院患者（n=180）中进行，这些患者被DSM-IV-TR诊断为双相情感障碍，当前发作的躁狂伴有或不伴有精神病性特征（不包括快速循环发作和混合发作）。研究期间未使用抗精神病药物。受试者口服固定剂量的别嘌呤醇600 mg/天（n=60）、双嘧达莫200 mg/天（n=60）或添加锂的安慰剂（n=60），持续4周。在基线和第7、14、21和28天对受试者进行评分，使用青年躁狂症评定量表（YMRS）作为主要疗效指标。这项研究是在2003年9月至2006年9月间进行的。采用线性模型分析（d=0.32, 95% ci = 0.07 ~ 0.57），与安慰剂相比，别嘌呤醇组从基线到第21天（p< 0.001）和第28天（p= 0.003）的YMRS评分平均下降幅度更大。别嘌呤醇组的缓解率明显高于双嘧达莫组和安慰剂组（p=0.008）。即使在安慰剂组，锂也显示出显著的抗躁狂功效。别嘌呤醇组血浆尿酸水平降低与抗躁狂效果显著正相关（p<0.001）。别嘌呤醇是临床有效且耐受性良好的躁狂发作与锂的辅助治疗，可能是治疗急性躁狂的一种替代方法，特别是对于那些抗精神病药物存在耐受性和安全性问题的患者。目前的结果强烈支持嘌呤能系统参与双相情感障碍的病理生理和治疗。别嘌呤醇与标准情绪稳定剂在躁狂症和维持中的比较的进一步安慰剂对照研究是必要的。
The therapeutics for Bipolar Disorders (BD) is still far from adequate and new options with improved effectiveness, safety and tolerability in a wide range of patients are necessary. Preliminary data have suggested a role for dysfunctions targeting at the purinergic system in mood disorders. This study aimed to evaluate the efficacy and tolerability of the purinergic agents allopurinol and dipyridamole combined with lithium in bipolar mania. A randomized, placebo-controlled, double-blind study was performed in adult inpatients (n=180) with a DSM-IV-TR diagnosis of bipolar disorder, current episode manic with or without psychotic features (rapid cyclers and mixed episodes were not included). No antipsychotic agent was used during the study. Subjects were given fixed oral doses of either allopurinol 600 mg/day (n=60), dipyridamole 200 mg/day (n=60), or placebo (n=60) added to lithium for 4 weeks. Subjects were rated at baseline and days 7, 14, 21 and 28 using the Young Mania Rating Scale (YMRS) as the primary efficacy measure. The study was conducted between September 2003 and September 2006. Allopurinol resulted in greater mean reductions in YMRS scores from baseline to day 21 (p<.001) and day 28 (p=.003) compared with placebo using a linear model analysis (d=0.32, 95% C.I. = 0.07 to 0.57). Remission rates were significantly higher for allopurinol compared to dipyridamole and placebo (p=0.008). Lithium showed a significant antimanic efficacy even in the placebo group. Decrease in plasma uric acid levels showed a significant positive association with antimanic effects in the allopurinol group (p<0.001). Allopurinol is clinically effective and well-tolerated adjunctively with lithium in manic episodes and may represent an alternative approach in the treatment of acute mania, especially for those presenting tolerability and safety issues with antipsychotics. The present results strongly support the involvement of the purinergic system in the pathophysiology and therapeutics of Bipolar Disorder. Further placebo-controlled studies with allopurinol compared with standard mood-stabilizers in mania and maintenance are warranted.
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影响因子：
7.3
作者：
DALY, JW
通讯作者：
DALY, JW
影响因子：
4.1
作者：
Lara, DR;Belmonte-de-Abreu, P;Souza, DO
通讯作者：
Souza, DO
影响因子：
4.7
作者：
Machado-Vieira, R;Lara, DR;Kapczinski, F
通讯作者：
Kapczinski, F
DOI：
10.1002/ajmg.b.30303
发表时间：
2006-06-05
影响因子：
2.8
作者：
Barden, Nicholas;Harvey, Mario;Mueller-Myhsok, Bertram
通讯作者：
Mueller-Myhsok, Bertram
影响因子：
5.4
作者：
Akhondzadeh, Shahin;Milajerdi, Mehdi Rafiee;Tehrani-Doost, Mehdi
通讯作者：
Tehrani-Doost, Mehdi