Fessel Jeffrey
Department of Medicine, University of California, 2069 Filbert Street, San Francisco, CA, 94123, USA.
Discov Ment Health. 2023 Jan 5;3(1):3. doi: 10.1007/s44192-022-00029-8.
Pharmacotherapy for most psychiatric conditions was developed from serendipitous observations of benefit from drugs prescribed for different reasons. An algorithmic approach to formulating pharmacotherapy is proposed, based upon which combination of changed activities by brain cell-types is dominant for any particular condition, because those cell-types contain and surrogate for genetic, metabolic and environmental information, that has affected their function. The algorithm performs because functions of some or all the affected cell-types benefit from several available drugs: clemastine, dantrolene, erythropoietin, fingolimod, fluoxetine, lithium, memantine, minocycline, pioglitazone, piracetam, and riluzole PROCEDURES/FINDINGS: Bipolar disorder, major depressive disorder, schizophrenia, Alzheimer's disease, and post-traumatic stress disorder, illustrate the algorithm; for them, literature reviews show that no single combination of altered cell-types accounts for all cases; but they identify, for each condition, which combination occurs most frequently, i.e., dominates, as compared with other possible combinations. Knowing the dominant combination of altered cell-types in a particular condition, permits formulation of therapy with combinations of drugs taken from the above list. The percentage of patients who might benefit from that therapy, depends upon the frequency with which the dominant combination occurs in patients with that particular condition.
Knowing the dominant combination of changed cell types in psychiatric conditions, permits an algorithmically formulated, rationally-based treatment. Different studies of the same condition often produce discrepant results; all might be correct, because identical clinical phenotypes result from different combinations of impaired cell-types, thus producing different results. Clinical trials would validate both the proposed concept and choice of drugs.
大多数精神疾病的药物治疗是基于对因不同原因开的药物疗效的偶然观察而发展起来的。本文提出了一种制定药物治疗方案的算法方法,该方法基于脑细胞类型活动变化的哪种组合在任何特定疾病中占主导地位,因为这些细胞类型包含并替代了影响其功能的遗传、代谢和环境信息。该算法之所以可行,是因为部分或所有受影响的细胞类型的功能会从几种现有药物中获益:氯马斯汀、丹曲林、促红细胞生成素、芬戈莫德、氟西汀、锂盐、美金刚、米诺环素、吡格列酮、吡拉西坦和利鲁唑。
程序/发现:双相情感障碍、重度抑郁症、精神分裂症、阿尔茨海默病和创伤后应激障碍可说明该算法;对于这些疾病,文献综述表明,没有一种单一的细胞类型改变组合能解释所有病例;但它们确定了每种疾病中哪种组合出现得最频繁,即与其他可能的组合相比占主导地位。了解特定疾病中细胞类型改变的主导组合,有助于用上述列表中的药物组合来制定治疗方案。可能从该治疗方案中获益的患者百分比,取决于该主导组合在患有该特定疾病的患者中出现的频率。
了解精神疾病中细胞类型改变的主导组合,有助于制定基于算法的、合理的治疗方案。对同一疾病的不同研究往往会产生不一致的结果;所有结果可能都是正确的,因为相同的临床表型是由受损细胞类型的不同组合导致的,从而产生不同的结果。临床试验将验证所提出的概念和药物选择。