Department of Psychiatry and Psychotherapy, Heinrich-Heine-University, Düsseldorf, Rhineland State Clinics Düsseldorf, Bergische Landstraße 2, D-40629 Düsseldorf, Germany.
J Clin Psychiatry. 2011 Feb;72(2):205-18. doi: 10.4088/JCP.09m05459yel. Epub 2010 Jun 29.
After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia.
A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits).
Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P < .001) were significantly higher in the intermittent treatment group than in the maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer side effects, particularly extrapyramidal side effects.
Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse, even in stable first-episode patients after 1 year of maintenance treatment, and should be the preferred treatment option. However, about 50% of patients remain stable at a significantly lower drug dose and show fewer side effects, and a substantial proportion refuse maintenance treatment. Alternative long-term treatment strategies, including targeted intermittent treatment, should therefore be provided in individual cases.
clinicaltrials.gov Identifier: NCT00159120.
精神分裂症首次发病发作后，建议进行至少 1 年的抗精神病药物维持治疗。对于后续最佳治疗的证据仍然很少。靶向间歇性治疗在预防多次发作患者复发方面被发现不如连续治疗有效；然而，我们之前一项研究的事后分析表明，两种治疗方法在首发患者中的疗效相当。因此，本研究旨在前瞻性比较 ICD-10 诊断的首发精神分裂症患者进一步维持治疗和靶向间歇性治疗的预防复发疗效。
在德国精神分裂症研究网络内进行了一项随机对照试验。入组筛查于 2000 年 11 月至 2004 年 5 月进行。抗精神病药物维持治疗 1 年后，稳定的首发患者被随机分配接受 12 个月的进一步维持治疗或逐步停药和靶向间歇性治疗。在出现即将复发的前驱症状时，两组患者均根据决策算法接受早期药物干预。主要结局指标为复发（阳性和阴性综合征量表阳性评分增加>10，临床总体印象-变化评分≥6，以及功能总体评估评分下降>20，在两次就诊之间）。
96 名首发患者中，只有 44 名符合分配治疗条件（维持治疗组 23 名；间歇性治疗组 21 名）。间歇性治疗组的复发率（19% vs 0%；P =.04）和恶化率（高达 57% vs 4%；P <.001）显著高于维持治疗组，但生活质量评分相当。间歇性治疗组患者接受的抗精神病药物量明显较低（以氟哌啶醇等效物计；P <.001），且倾向于出现较少的副作用，尤其是锥体外系副作用。
维持治疗在预防复发方面比靶向间歇性治疗更有效，即使在首发后 1 年进行维持治疗的稳定患者中也是如此，应作为首选治疗方案。然而，约 50%的患者在显著较低的药物剂量下仍保持稳定，且副作用较少，且相当一部分患者拒绝维持治疗。因此，应在个别情况下提供包括靶向间歇性治疗在内的替代长期治疗策略。
clinicaltrials.gov 标识符：NCT00159120。
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