Division of Psychiatry, Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva.
J Clin Psychiatry. 2013 Dec;74(12):1224-32. doi: 10.4088/JCP.12m08160.
The limitations of antipsychotic therapy in schizophrenia and schizoaffective disorder led to the investigation of the putative utility of pharmacologic augmentation strategies. The antitumor agent bexarotene via nuclear retinoid X receptor (RXR) activation might modulate numerous metabolic pathways involved in the pathogenesis of schizophrenia and schizoaffective disorder. This trial aimed to investigate efficacy and safety of add-on bexarotene to ongoing antipsychotic treatment of patients with schizophrenia or schizoaffective disorder.
Ninety inpatients and outpatients that met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder participated in a 6-week, double-blind, randomized, placebo-controlled multicenter study. Bexarotene (75 mg/d) was added to ongoing antipsychotic treatment from October 2008 to December 2010. The reduction in the severity of symptoms on the Positive and Negative Syndrome Scale (PANSS) was a primary outcome. Secondary outcomes included general functioning, quality of life, and side effect scales.
Seventy-nine participants (88%) completed the protocol. Controlling for antipsychotic agents, a mixed model showed that patients who received adjunctive bexarotene had significantly lower PANSS positive scale scores compared to patients who received placebo (F = 8.6, P = .003; treatment arms × time, F = 2.7, P = .049), with moderate effect size (d = 0.48; 95% CI,0.04-0.93). Patients with mean or higher baseline PANSS positive scale scores and patients who did not take lipid-reducing agents revealed greater amelioration of positive symptoms (F = 7.4, P = .008). Other symptoms and secondary outcome measures were not affected by adjunctive bexarotene. Bexarotene was well tolerated, though 2 reversible side effects were reported: a significant increase in total cholesterol levels (P < .001) and a decrease in total thyroxine levels (P < .001).
Bexarotene might potentially be a novel adjuvant therapeutic strategy for schizophrenia, particularly for the reduction of positive symptoms. The potential benefits and risks of ongoing administration of bexarotene warrant further evaluation.
ClinicalTrials.gov identifier: NCT00535574.
抗精神病药物治疗在精神分裂症和分裂情感障碍中的局限性促使人们研究潜在的药物增效策略。抗肿瘤药物贝沙罗汀通过核视黄醇 X 受体 (RXR) 激活可能调节参与精神分裂症和分裂情感障碍发病机制的许多代谢途径。本试验旨在研究贝沙罗汀作为增效剂添加到正在进行的抗精神病治疗中对精神分裂症或分裂情感障碍患者的疗效和安全性。
90 名符合 DSM-IV-TR 精神分裂症或分裂情感障碍标准的住院和门诊患者参加了一项为期 6 周、双盲、随机、安慰剂对照的多中心研究。从 2008 年 10 月至 2010 年 12 月，贝沙罗汀（75mg/d）添加到正在进行的抗精神病治疗中。阳性和阴性综合征量表（PANSS）严重程度的降低是主要结果。次要结果包括一般功能、生活质量和副作用量表。
79 名参与者（88%）完成了方案。控制抗精神病药物后，混合模型显示接受辅助贝沙罗汀治疗的患者与接受安慰剂治疗的患者相比，PANSS 阳性量表评分显著降低（F=8.6，P=.003；治疗臂×时间，F=2.7，P=.049），具有中等效应大小（d=0.48；95%CI，0.04-0.93）。基线 PANSS 阳性量表评分较高的患者和未服用降脂药物的患者的阳性症状改善更为明显（F=7.4，P=.008）。辅助贝沙罗汀对其他症状和次要结局指标没有影响。贝沙罗汀耐受性良好，尽管报告了 2 种可逆的副作用：总胆固醇水平显著升高（P<.001）和总甲状腺素水平降低（P<.001）。
贝沙罗汀可能是精神分裂症的一种新的辅助治疗策略，特别是用于减轻阳性症状。正在进行的贝沙罗汀给药的潜在益处和风险需要进一步评估。
ClinicalTrials.gov 标识符：NCT00535574。
