Cowen Philip J
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
Curr Top Behav Neurosci. 2024;66:1-19. doi: 10.1007/7854_2023_447.
The widespread adoption of selective serotonin reuptake inhibitors (SSRIs) as first-line pharmacological treatments in the management of clinical depression transformed the landscape of drug therapy for this condition. SSRIs are safer and better tolerated than the tricyclic antidepressants (TCAs) that they replaced. However, they have limitations that may have placed a ceiling on the expectations of first-line pharmacological treatment. Notable problems with SSRIs include induction of anxiety on treatment initiation, delayed onset of significant therapeutic effect, sexual dysfunction, sleep disturbance and overall modest efficacy. The latter is linked with an inability of SSRIs to effectively treat syndromes of anhedonia and cognitive impairment. Combined serotonin and noradrenaline reuptake inhibitors (SNRIs), such as venlafaxine, have produced some limited improvements over SSRIs in efficacy, at the cost of a greater side-effect burden. Attempts to supplement serotonin reuptake activity with actions at serotonin receptor sub-types have not yet yielded substantial benefits; however, vortioxetine may provide more utility in the management of cognitive impairment. Future advances might come from the development of SNRIs, which more closely mimic the actions of effective TCAs. There may also be possible benefits to be derived from combining SSRIs with 5-HT receptor agonists and 5-HT receptor antagonists.
选择性5-羟色胺再摄取抑制剂（SSRI）作为临床抑郁症管理中的一线药物治疗方法被广泛采用，改变了这种疾病的药物治疗格局。SSRI比它们所取代的三环类抗抑郁药（TCA）更安全，耐受性更好。然而，它们存在局限性，可能限制了一线药物治疗的预期效果。SSRI的显著问题包括治疗开始时引发焦虑、显著治疗效果起效延迟、性功能障碍、睡眠障碍以及总体疗效一般。后者与SSRI无法有效治疗快感缺失和认知障碍综合征有关。5-羟色胺和去甲肾上腺素再摄取抑制剂（SNRI），如文拉法辛，在疗效上比SSRI有一些有限的改善，但副作用负担更大。试图通过作用于5-羟色胺受体亚型来补充5-羟色胺再摄取活性尚未产生实质性益处；然而，伏硫西汀在认知障碍管理中可能更有用。未来的进展可能来自于开发更接近有效TCA作用的SNRI。将SSRI与5-羟色胺受体激动剂和5-羟色胺受体拮抗剂联合使用也可能有好处。
