Meltzer H Y, Lindenmayer J-P, Kwentus J, Share D B, Johnson R, Jayathilake K
Northwestern Feinberg School of Medicine, Chicago, IL, United States.
New York University School of Medicine, New York, NY, United States.
Schizophr Res. 2014 Apr;154(1-3):14-22. doi: 10.1016/j.schres.2014.02.015. Epub 2014 Mar 12.
It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta®, RLAI). One hundred sixty TRS patients selected for persistent moderate-severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100mg, would be more effective than RLAI, 50mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone+9-hydroxyrisperidone, during treatment with RLAI 100mg, were comparable to those for 6-8 mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥ 50-100mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥ six months.
有人提出，除氯氮平外的非典型抗精神病药物（A-APD）可能对改善某些难治性精神分裂症（TRS）患者的阳性症状有效，前提是与对非TRS（NTRS）患者无效的药物相比，其剂量更高且试验持续时间更长。本研究使用长效注射用利培酮（维思通长效针剂，RLAI）对这一假设进行了验证。在一项为期6个月的门诊双盲多中心试验中，160例因持续存在中度至重度妄想或幻觉或两者皆有而入选的TRS患者被随机分为接受每两周一次50mg或100mg的RLAI治疗。我们假设100mg的RLAI比50mg的RLAI更有效。然而，两种剂量在阳性和阴性症状量表（PANSS）总分、阳性和阴性分量表得分以及关键认知、整体和功能指标方面均产生了具有临床意义的等效改善，且在研究过程中反应逐渐增加，这证实了较长的临床试验持续时间对TRS患者的价值，但并未证明高剂量的优越性。总体缓解率与先前报道的氯氮平和另一种A-APD高剂量奥氮平在TRS中的缓解率相当。两种剂量的RLAI耐受性均良好，锥体外系副作用极小，脱落率低。在接受100mg RLAI治疗期间，活性成分利培酮+9-羟利培酮的血浆水平与口服6-8mg/日利培酮的血浆水平相当，而口服利培酮对TRS无效。应进一步研究每两周≥50 - 100mg的RLAI，并将其与氯氮平和口服利培酮在TRS患者中进行比较，治疗持续时间≥6个月。
