De Giorgi Riccardo, Waters Shona, Gillespie Amy L, Quinton Alice M G, Colwell Michael J, Murphy Susannah E, Cowen Philip J, Harmer Catherine J
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Psychol Med. 2025 May 22;55:e155. doi: 10.1017/S0033291725001187.
Statins are among the most prescribed medications worldwide. Both beneficial (e.g. antidepressant and pro-cognitive) and adverse (e.g. depressogenic and cognitive-impairing) mental health outcomes have been described in clinical studies. The underlying neuropsychological mechanisms, whether positive or negative, are, however, not established. Clarifying such activities has implications for the safe prescribing and repurposing potential of these drugs, especially in people with depression.
In this double-blind, randomized, placebo-controlled experimental medicine study, we investigated the effects of simvastatin on emotional processing, reward learning, working memory, and waking salivary cortisol (WSC) in 101 people at-risk for depression due to reported high loneliness scores (mean 7.3 ± 1.2 on the UCLA scale). This trial was largely conducted during periods of social distancing due to the COVID-19 pandemic (July 2021-February 2023), and we employed a fully remote design within a UK-wide sample.
High retention rates, minimal outlier data, and typical main effects of task condition (e.g. emotion) were seen in all cognitive tasks, indicating this approach was comparable to in-person testing. After 28 days, we found no statistically significant differences (F's < 3.0, p's > 0.20) for any of the measures of emotional processing, reward learning, working memory, and WSC.
Study results do not substantiate concerns regarding adverse neuropsychiatric events due to statins and support the safety of their prescribing in at-risk populations. Although other unmeasured cognitive processes may be involved, our null findings are also in line with more recent clinical evidence suggesting statins do not show antidepressant or pro-cognitive efficacy.
他汀类药物是全球处方量最多的药物之一。临床研究中已描述了其对心理健康有益（如抗抑郁和促进认知）和有害（如致抑郁和损害认知）的结果。然而，无论是积极还是消极的潜在神经心理学机制均未明确。阐明这些作用对于这些药物的安全处方和重新利用潜力具有重要意义，尤其是在抑郁症患者中。
在这项双盲、随机、安慰剂对照的实验医学研究中，我们调查了辛伐他汀对101名因报告的高孤独感得分（加州大学洛杉矶分校量表平均为7.3±1.2）而有抑郁风险的人的情绪加工、奖赏学习、工作记忆和清醒时唾液皮质醇（WSC）的影响。由于2019冠状病毒病大流行（2021年7月至2023年2月），该试验主要在社交距离期间进行，我们在全英国范围内的样本中采用了完全远程的设计。
在所有认知任务中均观察到高保留率、极少的异常值数据以及任务条件（如情绪）的典型主效应，表明该方法与面对面测试相当。28天后，我们发现情绪加工、奖赏学习、工作记忆和WSC的任何测量指标均无统计学显著差异（F值<3.0，p值>0.20）。
研究结果并未证实对他汀类药物导致不良神经精神事件的担忧，并支持在高危人群中处方他汀类药物的安全性。尽管可能涉及其他未测量的认知过程，但我们的阴性结果也与最近的临床证据一致，表明他汀类药物未显示出抗抑郁或促进认知的疗效。
