Sha'ar Menashe Mental Health Center, Hadera, Israel; The Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Psychiatry Clin Neurosci. 2014 Jun;68(6):432-40. doi: 10.1111/pcn.12150. Epub 2014 Feb 18.
Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA.
Sixty out- and inpatients who met DSM-IV criteria for SZ/SA, with suboptimal response to antipsychotics were recruited for an 8-week, double-blind, randomized, placebo-controlled, two-center add-on trial, that was conducted between 2008 and 2011. Participants were randomized to receive either pregnenolone (50 mg/day) or placebo added on to antipsychotic medications. The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores. Secondary outcomes included assessments of functioning, and side-effects.
Analysis was by linear mixed model. Fifty-two participants (86.7%) completed the trial. Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (d = 0.79). Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0.010). Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (d = 0.57), especially on blunted affect, avolition and anhedonia domain scores. Other symptoms, functioning, and side-effects were not significantly affected by adjunctive pregnenolone. Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation. Pregnenolone was well tolerated.
Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers. Further studies are warranted.
由于抗精神病药物经常反应不足，近期发病的精神分裂症（SZ）和分裂情感障碍（SA）的治疗具有挑战性。本研究旨在测试神经甾体孕烯醇酮在近期发病的 SZ/SA 患者中的疗效和安全性。
2008 年至 2011 年期间，我们进行了一项为期 8 周、双盲、随机、安慰剂对照、两中心的附加试验，共招募了 60 名符合 DSM-IV 精神分裂症/分裂情感障碍标准、抗精神病药物治疗效果不佳的门诊和住院患者。参与者被随机分配接受孕烯醇酮（50mg/天）或安慰剂，附加于抗精神病药物治疗。主要结局指标为阳性和阴性症状量表（PANSS）和阴性症状评定量表（SANS）评分。次要结局包括功能评估和副作用。
分析采用线性混合模型。52 名参与者（86.7%）完成了试验。与安慰剂相比，附加孕烯醇酮可显著降低 PANSS 阴性症状评分，具有中等的效应大小（d=0.79）。在未同时使用情绪稳定剂的患者中，在孕烯醇酮治疗的第 6 和第 8 周观察到显著改善（手臂×就诊×情绪稳定剂；P=0.010）。同样，与安慰剂相比，孕烯醇酮显著降低了 SANS 评分（d=0.57），特别是在迟钝情感、意志减退和快感缺失的领域评分。其他症状、功能和副作用没有因附加孕烯醇酮而受到显著影响。抗精神病药物、苯二氮䓬类药物和性别与孕烯醇酮增效无关。孕烯醇酮耐受良好。
因此，附加孕烯醇酮可降低近期发病的精神分裂症和分裂情感障碍的阴性症状严重程度，尤其是在未同时使用情绪稳定剂的患者中。需要进一步的研究。
