Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Bipolar Disord. 2012 Mar;14(2):206-10. doi: 10.1111/j.1399-5618.2012.01001.x.
Allopurinol promotes the salvage of purines, possibly increasing endogenous adenosine levels. Recent studies suggest that adenosine has neuroprotective and inhibitory effects. Two previous inpatient trials demonstrated that allopurinol has anti-manic activity. Our objective was to test allopurinol as an adjunct to standard medications in bipolar disorder manic outpatients.
In this double-blind, placebo-controlled trial, 27 subjects who met DSM-IV criteria for bipolar disorder and scored ≥ 14 on the Young Mania Rating Scale (YMRS) were randomized to augmentation with allopurinol or placebo for six weeks. The primary efficacy measure was the YMRS. The primary safety measure was the Treatment Emergent Symptom Scale.
The effect of allopurinol augmentation in decreasing mean YMRS scores was modest, with an overall effect size of -0.25 (Cohen's d). Allopurinol-treated individuals who abstained from caffeine (n = 4) had a greater decrease in YMRS scores (-15.3 ± 1.8) than subjects using caffeine (n = 5) (-9.6 ± 3.4, p = 0.219), with an effect size of -0.86.
In this small outpatient pilot study, allopurinol augmentation did not show a statistically significant improvement over placebo in attenuating manic symptoms. Subjects with restricted caffeine use showed a greater effect size compared to caffeine users. This finding may be interpreted as corroborating the hypothesized mechanism of action of allopurinol's anti-manic effect in previous studies.
别嘌醇促进嘌呤的补救，可能会增加内源性腺苷水平。最近的研究表明，腺苷具有神经保护和抑制作用。两项先前的住院试验表明，别嘌醇具有抗躁狂活性。我们的目的是测试别嘌醇作为双相情感障碍躁狂症门诊患者标准药物的辅助治疗。
在这项双盲、安慰剂对照试验中，27 名符合 DSM-IV 双相情感障碍标准且 Young 躁狂评定量表（YMRS）得分≥14 的患者被随机分为别嘌醇或安慰剂组，为期 6 周。主要疗效指标是 YMRS。主要安全性指标是治疗出现的症状量表。
别嘌醇增效治疗对降低 YMRS 评分的效果中等，总体效应大小为-0.25（Cohen's d）。避免使用咖啡因的别嘌醇治疗者（n=4）YMRS 评分下降幅度更大（-15.3±1.8），而使用咖啡因的患者（n=5）的降幅较小（-9.6±3.4，p=0.219），效应大小为-0.86。
在这项小型门诊试验中，别嘌醇增效治疗与安慰剂相比，在减轻躁狂症状方面并未显示出统计学上的显著改善。限制咖啡因使用的患者与咖啡因使用者相比，效果大小更大。这一发现可以解释为支持之前研究中别嘌醇抗躁狂作用的假设作用机制。
