Colita Cezar-Ivan, Hermann Dirk M, Filfan Madalina, Colita Daniela, Doepnner Thorsten R, Tica Oana, Glavan Daniela, Popa-Wagner Aurel
Doctoral School, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania.
Department of Neurology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
Clocks Sleep. 2024 Nov 5;6(4):635-655. doi: 10.3390/clockssleep6040043.
In many medical settings, medications are typically administered in the morning or evening, aligning with patients' daily routines. This practice does not stem from chronotherapy, which involves scheduling drug administration to enhance its effectiveness, but rather from the way clinical operations are structured. The timing of drug administration can significantly affect a medication's effectiveness and side effects, with the impact varying by up to ten times based on circadian rhythms. Disorders such as major depression, bipolar disorder, and schizophrenia are linked to disruptions in these rhythms. Recent studies have found that circadian dysfunctions, including genetic and neurohumoral changes, underlie many psychiatric conditions. Issues such as an altered glucocorticoid rhythm due to impaired HPA axis function, disturbed melatonin balance, and sleep disturbances have been noted in psychotic disorders. Furthermore, mood disorders have been associated with changes in the expression of circadian rhythm genes such as , , and . Considering that the absorption, biodistribution, effects on target organs, half-life, metabolism, and elimination of drugs are all influenced by the body's circadian rhythms, this narrative review explores the optimal timing of medication administration to maximize efficacy and minimize side effects in the treatment of psychiatric disorders. By closely monitoring circadian variations in cortisol, melatonin, and key clock genes, as well as by deepening our understanding of the metabolisms and pharmacokinetics of antipsychotic medications, we propose a chronotherapy approach for psychiatric patients that could significantly enhance patient care.
在许多医疗环境中，药物通常在早晨或晚上给药，这与患者的日常作息相契合。这种做法并非源于时间治疗法（即安排药物给药时间以提高其疗效），而是源于临床操作的组织方式。药物给药时间可显著影响药物的疗效和副作用，其影响因昼夜节律而变化高达十倍。重度抑郁症、双相情感障碍和精神分裂症等疾病与这些节律的紊乱有关。最近的研究发现，包括基因和神经体液变化在内的昼夜节律功能障碍是许多精神疾病的基础。在精神障碍中已注意到诸如由于下丘脑 - 垂体 - 肾上腺（HPA）轴功能受损导致糖皮质激素节律改变、褪黑素平衡紊乱和睡眠障碍等问题。此外，情绪障碍与昼夜节律基因如 、 和 的表达变化有关。鉴于药物的吸收、生物分布、对靶器官的作用、半衰期、代谢和消除均受人体昼夜节律影响，本叙述性综述探讨了在精神疾病治疗中药物给药的最佳时间，以最大化疗效并最小化副作用。通过密切监测皮质醇、褪黑素和关键生物钟基因的昼夜变化，以及加深我们对抗精神病药物代谢和药代动力学的理解，我们为精神科患者提出一种时间治疗方法，可显著改善患者护理。
