Formerly of Shire Development LLC, Wayne, PA, USA.
Neuropsychopharmacology. 2013 Oct;38(11):2140-9. doi: 10.1038/npp.2013.111. Epub 2013 May 8.
Negative symptoms of schizophrenia (NSS), related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex, are predictive of poor outcomes and have no effective treatment. Use of dopamine-enhancing drugs (eg, psychostimulants) has been limited by potential adverse effects. This multicenter study examined lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, as adjunctive therapy to antipsychotics in adults with clinically stable schizophrenia and predominant NSS. Outpatients with stable schizophrenia, predominant NSS, limited positive symptoms, and maintained on stable atypical antipsychotic therapy underwent a 3-week screening, 10-week open-label adjunctive LDX (20-70 mg/day), and 4-week, double-blind, randomized, placebo-controlled withdrawal. Efficacy measures included a modified Scale for the Assessment of Negative Symptoms (SANS-18) and Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Ninety-two participants received open-label LDX; 69 received double-blind therapy with placebo (n=35) or LDX (n=34). At week 10 (last observation carried forward; last open-label visit), mean (95% confidence interval) change in SANS-18 scores was -12.9 (-15.0, -10.8; P<0.0001). At week 10, 52.9% of participants demonstrated a minimum of 20% reduction from baseline in SANS-18 score. Open-label LDX was also associated with significant improvement in PANSS total and subscale scores. During the double-blind/randomized-withdrawal phase, no significant differences (change from randomization baseline) were found between placebo and LDX in SANS-18 or PANSS subscale scores. In adults with clinically stable schizophrenia, open-label LDX appeared to be associated with significant improvements in negative symptoms without positive symptom worsening. Abrupt LDX discontinuation was not associated with positive or negative symptom worsening. Confirmation with larger controlled trials is warranted.
精神分裂症的阴性症状（NSS）与中皮质通路和前额叶皮质的低多巴胺活性有关，与不良预后相关，且目前尚无有效的治疗方法。使用多巴胺增强药物（例如，精神兴奋剂）受到潜在不良反应的限制。这项多中心研究检查了右苯丙胺 dimesylate（LDX），一种 d-苯丙胺前体药物，作为辅助治疗与抗精神病药物联合治疗临床稳定的精神分裂症和主要 NSS 患者。稳定的精神分裂症、主要 NSS、有限的阳性症状且维持稳定的非典型抗精神病治疗的门诊患者接受了 3 周的筛选、10 周的开放标签辅助 LDX（20-70mg/天）以及 4 周的双盲、随机、安慰剂对照停药。疗效评估包括改良的阴性症状评定量表（SANS-18）和阳性和阴性综合征量表（PANSS）总分和分量表评分。92 名参与者接受了开放标签 LDX；69 名参与者接受了双盲治疗，包括安慰剂（n=35）或 LDX（n=34）。在第 10 周（末次观察推进；最后一次开放标签访视），SANS-18 评分的平均（95%置信区间）变化为-12.9（-15.0，-10.8；P<0.0001）。在第 10 周时，52.9%的参与者的 SANS-18 评分从基线下降至少 20%。开放标签 LDX 也与 PANSS 总分和分量表评分的显著改善相关。在双盲/随机撤药阶段，与安慰剂相比，LDX 在 SANS-18 或 PANSS 分量表评分方面无显著差异（从随机基线的变化）。在临床稳定的精神分裂症成年患者中，开放标签 LDX 似乎与阴性症状的显著改善相关，而不导致阳性症状恶化。LDX 突然停药与阳性或阴性症状恶化无关。需要更大规模的对照试验来证实。
