Kapur Ajay
University of Oxford, Oxford, UK.
CNS Drugs. 2020 Oct;34(10):1045-1062. doi: 10.1007/s40263-020-00758-w.
Nootropics are drugs used to either treat or benefit cognition deficits. Among this class, methylphenidate is a popular agent, which acts through indirect dopaminergic and noradrenergic agonism and, therefore, is proposed to enhance performance in catecholamine-dependent cognitive domains such as attention, memory and prefrontal cortex-dependent executive functions. However, investigation into the efficacy of methylphenidate as a cognitive enhancer has yielded variable results across all domains, leading to debate within the scientific community surrounding its off-label use in healthy individuals seeking scholaristic benefit or increased productivity. Through analysis of experimental data and methodological evaluation, it is apparent that there are dose-, task- and domain-dependent considerations surrounding the use of methylphenidate in healthy individuals, whereby tailored dose administration is likely to provide benefit on an individual basis dependent on the domain of cognition in which benefit is required. Additionally, it is apparent that there are subjective effects of methylphenidate, which may increase user productivity irrespective of cognitive benefit. Whilst there is not extensive study in healthy older adults, it is plausible that there are dose-dependent benefits to methylphenidate in older adults in selective cognitive domains that might improve quality of life and reduce fall risk. Methylphenidate appears to produce dose-dependent benefits to individuals with attention-deficit/hyperactivity disorder, but the evidence for benefit in Parkinson's disease and schizophrenia is inconclusive. As with any off-label use of pharmacological agents, and especially regarding drugs with neuromodulatory effects, there are inherent safety concerns; epidemiological and experimental evidence suggests there are sympathomimetic, cardiovascular and addictive considerations, which might further restrict their use within certain demographics.
益智药是用于治疗认知缺陷或使其受益的药物。在这类药物中，哌醋甲酯是一种常用药物，它通过间接的多巴胺能和去甲肾上腺素能激动作用发挥功效，因此被认为可以提高在儿茶酚胺依赖的认知领域（如注意力、记忆力和前额叶皮质依赖的执行功能）中的表现。然而，对哌醋甲酯作为认知增强剂疗效的研究在所有领域都产生了不同的结果，这引发了科学界对于其在寻求学术益处或提高生产力的健康个体中的非标签使用的争论。通过对实验数据的分析和方法学评估，很明显在健康个体中使用哌醋甲酯存在剂量、任务和领域依赖性的考量，据此量身定制的剂量给药可能会根据个体所需认知领域的不同而带来益处。此外，很明显哌醋甲酯存在主观效应，这可能会提高使用者的生产力，而与认知益处无关。虽然在健康老年人中没有广泛的研究，但哌醋甲酯在老年人的选择性认知领域可能存在剂量依赖性益处，这可能会改善生活质量并降低跌倒风险，这是有道理的。哌醋甲酯似乎对注意力缺陷/多动障碍患者产生剂量依赖性益处，但在帕金森病和精神分裂症中的益处证据尚无定论。与任何药物的非标签使用一样，尤其是对于具有神经调节作用的药物，存在固有的安全问题；流行病学和实验证据表明存在拟交感神经、心血管和成瘾性方面的考量，这可能会进一步限制它们在某些人群中的使用。
