Maraone Annalisa, Trebbastoni Alessandro, Di Vita Antonella, D'Antonio Fabrizia, De Lena Carlo, Pasquini Massimo
Sapienza University of Rome, Roma, Italy.
Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Rome, Italy.
JMIR Res Protoc. 2023 May 11;12:e39223. doi: 10.2196/39223.
Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions for decreasing distress. Symptoms can cause severe distress and functional impairment. OCD affects 2% to 3% of the population and is ranked within the 10 leading neuropsychiatric causes of disability. Cortico-striatal-thalamo-cortical circuitry dysfunction has been implicated in OCD, including altered brain activation and connectivity. Complex glutamatergic signaling dysregulation within cortico-striatal circuitry has been proposed in OCD. Data obtained by several studies indicate reduced glutamatergic concentrations in the anterior cingulate cortex, combined with overactive glutamatergic signaling in the striatum and orbitofrontal cortex. A growing number of randomized controlled trials have assessed the utility of different glutamate-modulating drugs as augmentation medications or monotherapies for OCD, including refractory OCD. However, there are relevant variations among studies in terms of patients' treatment resistance, comorbidity, age, and gender. At present, 4 randomized controlled trials are available on the efficacy of memantine as an augmentation medication for refractory OCD.
Our study's main purpose is to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of moderate to severe OCD. The study's second aim is to evaluate the effect of memantine on cognitive functions in patients with OCD. The third aim is to investigate if responses to memantine are modulated by variables such as gender, symptom subtypes, and the duration of untreated illness.
Investigators intend to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of patients affected by severe refractory OCD. Participants will be rated via the Yale-Brown Obsessive Compulsive Scale at baseline and at 2, 4, 6, 8, 10, and 12 months. During the screening period and T4 and T6 follow-up visits, all participants will undergo an extensive neuropsychological evaluation. The 52-week study duration will consist of 4 distinct periods, including memantine titration and follow-up periods.
Recruitment has not yet started. The study will be conducted from June 2023 to December 2024. Results are expected to be available in January 2025. Throughout the slow-titration period, we will observe the minimum effective dose of memantine, and the follow-up procedure will detail its residual efficacy after drug withdrawal.
The innovation of this research proposal is not limited to the evaluation of the efficacy and safety of memantine as an augmentation medication for OCD. We will also test if memantine acts as a pure antiobsessive medication or if memantine's ability to improve concentration and attention mimics an antiobsessive effect.
ClinicalTrials.gov NCT05015595; https://clinicaltrials.gov/ct2/show/NCT05015595.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/39223.
强迫症（OCD）是一种精神综合征，其特征是存在不必要的重复想法以及为减轻痛苦而反复进行的仪式化强迫行为。这些症状会导致严重的痛苦和功能障碍。强迫症影响2%至3%的人口，在导致残疾的十大神经精神病因中名列前茅。皮质-纹状体-丘脑-皮质回路功能障碍与强迫症有关，包括大脑激活和连接性的改变。有研究提出，皮质-纹状体回路中复杂的谷氨酸能信号失调与强迫症有关。多项研究获得的数据表明，前扣带回皮质中的谷氨酸能浓度降低，同时纹状体和眶额皮质中的谷氨酸能信号过度活跃。越来越多的随机对照试验评估了不同的谷氨酸调节药物作为强迫症（包括难治性强迫症）的增效药物或单一疗法的效用。然而，在患者的治疗抵抗性、合并症、年龄和性别方面，研究之间存在相关差异。目前，有4项关于美金刚作为难治性强迫症增效药物疗效的随机对照试验。
本研究的主要目的是进行一项双盲、随机、平行组、安慰剂对照的单中心试验，以评估美金刚作为选择性5-羟色胺再摄取抑制剂的增效剂在治疗中度至重度强迫症中的疗效和安全性。该研究的第二个目的是评估美金刚对强迫症患者认知功能的影响。第三个目的是研究性别、症状亚型和未治疗疾病持续时间等变量是否会调节对美金刚的反应。
研究人员打算进行一项双盲、随机、平行组、安慰剂对照的单中心试验，以评估美金刚作为选择性5-羟色胺再摄取抑制剂的增效剂在治疗重度难治性强迫症患者中的疗效和安全性。将在基线以及第2、4、6、8、10和12个月时通过耶鲁-布朗强迫症量表对参与者进行评分。在筛查期以及T4和T6随访期间，所有参与者都将接受全面的神经心理学评估。为期52周的研究将包括4个不同阶段，包括美金刚滴定期和随访期。
招募工作尚未开始。该研究将于2023年6月至2024年12月进行。预计2025年1月可获得结果。在整个缓慢滴定期，我们将观察美金刚的最低有效剂量，随访程序将详细说明停药后其残余疗效。
本研究方案的创新之处不仅在于评估美金刚作为强迫症增效药物的疗效和安全性。我们还将测试美金刚是否作为一种纯粹的抗强迫药物起作用，或者美金刚改善注意力和专注力的能力是否类似于抗强迫作用。
ClinicalTrials.gov NCT05015595；https://clinicaltrials.gov/ct2/show/NCT05015595。
国际注册报告识别码（IRRID）：PRR1-10.2196/39223。
