Division of Psychiatry, Chaim Sheba Medical Center, Tel-Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Bipolar Disord. 2014 Jun;16(4):441-7. doi: 10.1111/bdi.12202. Epub 2014 Apr 8.
An emerging body of evidence supports a role for dysfunctional purinergic neurotransmission in mood disorders. Adenosine agonists have been shown to have properties similar to those of dopamine antagonists; there is a well-characterized interaction between adenosine and dopamine receptors in the ventral striatum, and increasing adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors. Allopurinol increases adenosine levels in the brain, and hence is hypothesized to reduce the symptoms of mania. Two randomized, placebo-controlled trials administering add-on allopurinol to manic patients showed significantly greater improvements in Young Mania Rating Scale (YMRS) scores for drug compared to placebo, while a more recent, relatively small, add-on study showed negative results. Based on these data, our objective was to examine the efficacy of allopurinol as add-on treatment to mood stabilizers and/or antipsychotic agents in manic patients with bipolar disorder.
We performed a large, well-powered, multicenter, six-week, randomized, placebo-controlled trial of allopurinol added to mood stabilizers and/or antipsychotic agents in 180 patients with bipolar disorder in an acute manic episode.
Both groups showed improvement on the YMRS (effect size of 1.5 for placebo and 1.6 for allopurinol), with no difference observed between groups on YMRS scores (t = 0.28, p = 0.78). There was no difference in the proportion of patients who responded to treatment (defined as showing at least 50% improvement in YMRS score) between the two groups (p = 0.92), or in dropout rates (p = 0.84).
None of our patients received lithium. However, the side effects of lithium and its narrow therapeutic index made the use of lithium less common and, therefore, our study results reflect common current clinical practice. In the present study, we used a variety of antipsychotic and/or mood stabilizing treatments, to which we added allopurinol; one might hypothesize that add-on allopurinol has a different effect in combination with different antipsychotic agents or mood stabilizers.
The findings of this large, well-powered study do not support add-on allopurinol as a treatment for acute mania. This study did not test the efficacy of allopurinol as monotherapy.
越来越多的证据表明，嘌呤能神经传递功能障碍在心境障碍中起作用。已证明腺苷激动剂具有类似于多巴胺拮抗剂的特性；在腹侧纹状体中，存在着一种特征明确的腺苷和多巴胺受体相互作用，并且已经证明增加腺苷能传递可以降低多巴胺激动剂与多巴胺受体的亲和力。别嘌呤醇增加大脑中的腺苷水平，因此被假设可以减轻躁狂的症状。两项随机、安慰剂对照试验向躁狂患者添加辅助性别嘌呤醇治疗，结果显示药物治疗组在 Young Mania Rating Scale (YMRS) 评分上的改善明显优于安慰剂组，而最近一项相对较小的附加研究则显示出阴性结果。基于这些数据，我们的目的是研究别嘌呤醇作为双相情感障碍急性躁狂患者的心境稳定剂和/或抗精神病药物的附加治疗的疗效。
我们对 180 名处于急性躁狂发作的双相情感障碍患者进行了一项大型、有力、多中心、为期 6 周的随机、安慰剂对照试验，评估别嘌呤醇添加到心境稳定剂和/或抗精神病药物中的效果。
两组患者在 YMRS 上均有改善（安慰剂组的效应量为 1.5，别嘌呤醇组为 1.6），两组患者的 YMRS 评分无差异（t = 0.28，p = 0.78）。两组患者对治疗的反应率（定义为 YMRS 评分至少改善 50%）无差异（p = 0.92），或退出率（p = 0.84）无差异。
我们的患者均未接受锂治疗。然而，锂的副作用及其狭窄的治疗指数使得锂的使用不那么常见，因此我们的研究结果反映了当前常见的临床实践。在本研究中，我们使用了多种抗精神病药物和/或心境稳定剂治疗，并在此基础上添加了别嘌呤醇；人们可能会假设，添加别嘌呤醇与不同的抗精神病药物或心境稳定剂联合使用会有不同的效果。
这项大型、有力的研究结果不支持添加别嘌呤醇作为急性躁狂的治疗方法。本研究并未测试别嘌呤醇作为单一疗法的疗效。
