Prescrire Int. 2005 Aug;14(78):140-2.
(1) Lithium, the standard preventive treatment for patients with bipolar disorder, reduces the number of relapses and suicide attempts. (2) Olanzapine is the first neuroleptic to be approved in France for prevention of relapse in patients with bipolar disorder. Many neuroleptics are already used for this indication but their efficacy has not been established in comparative clinical trials. (3) One placebo-controlled double-blind trial involved 361 patients who were treated just after recovering from a manic episode. The trial was supposed to last 48 weeks, but only 146 patients were treated for more than 8 weeks. Therefore, the trial results, including an observed effect on mania, cannot be interpreted to imply long-term prevention. (4) One double-blind trial compared olanzapine plus a mood stabiliser with placebo plus a mood stabiliser in 344 patients who had recovered from an acute episode. Only 21 patients completed the 12-month trial, and the percentage of patients who had relapses (manic or depressive) did not differ significantly between the groups. (5) In a third double-blind trial, 431 patients in remission from a manic episode after treatment with olanzapine + lithium were treated for 12 months with lithium or olanzapine. This trial suggested that olanzapine was more effective in preventing depressive and manic relapses (30% of patients, compared to 38.8% with lithium), but only 171 patients completed the trial. Most dropouts were due to adverse events (19% with olanzapine, 26% with lithium). The impact of treatment on suicide risk was not studied. (6) In a fourth study, 101 patients in remission from a mixed or manic episode continued their initial treatment with olanzapine or sodium divalproate in double-blind manner for 11 months. The risk of relapse was not significantly different between the groups, but the study sample size was too small to tell whether or not the treatments were equally effective. (7) Trials focusing on prevention of relapse in patients with bipolar disorder confirmed the known adverse effects of olanzapine, including weight gain and QTc prolongation. Olanzapine was associated with more weight gain and sedation than lithium. Hyperglycaemia occurring on olanzapine can cause life-threatening ketoacidosis. (8) Lithium remains the standard treatment for preventing recurrent bipolar disorder. There is no firm evidence that olanzapine is more effective than a mood stabiliser after lithium failure, or that it boosts the efficacy of lithium.
(1) 锂盐是双相情感障碍患者的标准预防性治疗药物，可减少复发次数和自杀企图。(2) 奥氮平是法国首个获批用于预防双相情感障碍患者复发的抗精神病药物。许多抗精神病药物已用于该适应症，但它们的疗效尚未在比较性临床试验中得到证实。(3) 一项安慰剂对照双盲试验纳入了361例刚从躁狂发作中康复的患者。该试验本应持续48周，但只有146例患者接受治疗超过8周。因此，试验结果，包括对躁狂的观察到的效果，不能被解释为意味着长期预防。(4) 一项双盲试验在344例从急性发作中康复的患者中，将奥氮平加心境稳定剂与安慰剂加心境稳定剂进行了比较。只有21例患者完成了12个月的试验，两组中复发（躁狂或抑郁）的患者百分比没有显著差异。(5) 在第三项双盲试验中，431例在接受奥氮平 + 锂盐治疗后从躁狂发作中缓解的患者，用锂盐或奥氮平治疗12个月。该试验表明奥氮平在预防抑郁和躁狂复发方面更有效（30%的患者，锂盐组为38.8%），但只有171例患者完成了试验。大多数退出试验是由于不良事件（奥氮平组为19%，锂盐组为26%）。未研究治疗对自杀风险的影响。(6) 在第四项研究中，101例从混合或躁狂发作中缓解的患者以双盲方式继续使用奥氮平或丙戊酸钠进行初始治疗11个月。两组之间复发风险没有显著差异，但研究样本量太小，无法判断治疗是否同样有效。(7) 关注双相情感障碍患者复发预防的试验证实了奥氮平已知的不良反应，包括体重增加和QTc延长。奥氮平比锂盐导致更多的体重增加和镇静作用。奥氮平引起的高血糖可导致危及生命的酮症酸中毒。(8) 锂盐仍然是预防复发性双相情感障碍的标准治疗方法。没有确凿证据表明奥氮平在锂盐治疗失败后比心境稳定剂更有效，或者它能提高锂盐的疗效。
