Gopal Srihari, Gogate Jagadish, Pungor Katalin, Kim Edward, Singh Arun, Mathews Maju
Janssen Research and Development, LLC, Titusville, NJ, USA.
Medical Affairs, EMEA, Janssen-Cilag, Neuss, Germany.
Neuropsychiatr Dis Treat. 2020 Mar 6;16:681-690. doi: 10.2147/NDT.S226296. eCollection 2020.
Negative symptoms in schizophrenia are associated with impairments in social and cognitive functioning leading to substantial long-term disability. Available antipsychotic treatments have demonstrated only modest benefit in the improvement of negative symptoms.
To compare improvements in negative symptoms among patients treated with paliperidone palmitate 3-month (PP3M) or paliperidone palmitate 1-month (PP1M) long-acting injectable (LAI) formulations.
Data from a randomized double-blind (DB), phase-3, non-inferiority study in patients with schizophrenia were analyzed. Following screening, patients entered a 17-week open-label (OL) phase to receive flexibly dosed PP1M followed by a 48-week DB phase where patients were randomized (1:1) to receive either PP1M or PP3M. Positive and Negative Syndrome Scale (PANSS) total scores with emphasis on 7-item negative subscale scores for PP1M vs PP3M were assessed.
Of 1429 patients enrolled, 1016 were randomized to receive PP3M (n=504) or PP1M (n=512). At baseline, mean (SD) PANSS negative subscale was 23.2 (4.60) and negative symptom factor score was 22.3 (4.87), indicating moderate-to-severe negative symptoms. Negative subscale and symptoms factor scores showed continuous improvements throughout OL (15.9 [4.99]) and DB (14.9 [4.81]) phases. Mean (SD) changes from DB baseline in the PANSS negative subscale score were comparable between PP1M (-1.4 [3.67]) and PP3M (-1.4 [3.63]) treatment groups.
Treatment with PP3M or PP1M demonstrated comparable improvement in negative symptoms in patients with moderate-to-severe negative symptoms and in patients with prominent negative symptoms. Long-term treatment with PP3M demonstrated benefit, suggesting that continuous antipsychotic medication treatment for >1 year is needed to achieve greater benefit for negative symptoms.
ClinicalTrials.gov Identifier: NCT01515423.
精神分裂症的阴性症状与社交和认知功能障碍相关，会导致严重的长期残疾。现有的抗精神病药物治疗在改善阴性症状方面仅显示出有限的益处。
比较接受棕榈酸帕利哌酮3个月（PP3M）或棕榈酸帕利哌酮1个月（PP1M）长效注射（LAI）制剂治疗的患者在阴性症状方面的改善情况。
分析了一项针对精神分裂症患者的随机双盲（DB）3期非劣效性研究的数据。筛选后，患者进入为期17周的开放标签（OL）阶段，接受灵活剂量的PP1M治疗，随后进入为期48周的DB阶段，患者被随机（1:1）分配接受PP1M或PP3M治疗。评估了阳性和阴性症状量表（PANSS）总分，重点是PP1M与PP3M的7项阴性子量表得分。
在1429名入组患者中，1016名被随机分配接受PP3M（n = 504）或PP1M（n = 512）治疗。基线时，平均（标准差）PANSS阴性子量表评分为23.2（4.60），阴性症状因子评分为22.3（4.87），表明存在中度至重度阴性症状。阴性子量表和症状因子评分在整个OL阶段（15.9 [4.99]）和DB阶段（14.9 [4.81]）均持续改善。PP1M（-1.4 [3.67]）和PP3M（-1.4 [3.63]）治疗组在PANSS阴性子量表评分上从DB基线的平均（标准差）变化相当。
PP3M或PP1M治疗在中度至重度阴性症状患者和突出阴性症状患者的阴性症状改善方面表现相当。PP3M的长期治疗显示出益处，表明需要持续抗精神病药物治疗>1年才能在阴性症状方面获得更大益处。
ClinicalTrials.gov标识符：NCT01515423。
