Pardossi Simone, Fagiolini Andrea, Cuomo Alessandro
Department of Molecular Medicine, University of Siena School of Medicine, 53100 Siena, Italy.
Actas Esp Psiquiatr. 2025 May;53(3):621-631. doi: 10.62641/aep.v53i3.1880.
Bipolar disorder (BD) is characterized by the occurrence of manic/hypomanic and depressive episodes, with the latter having a significant impact on morbidity, mortality and overall quality of life. Current guidelines for bipolar depression provide limited treatment options, with only a few approved therapies. Despite these limitations, approximately 50-60% of individuals diagnosed with BD are prescribed antidepressants. However, the use of these medications remains controversial due to risks of manic induction, rapid cycling, and symptom destabilization. This review explores the neurotransmitter mechanisms underpinning the phases of BD, focusing on monoamines and assessing the efficacy and safety of different antidepressant medications in the treatment of bipolar depression. Norepinephrine and dopamine have been identified as neurotransmitters associated with both depressive and manic poles, with a proposed deficit in depression and an increase in mania. The evidence indicates that serotonin is deficient during depressive phases, yet its imbalance also manifests in mania. Selective serotonin reuptake inhibitors (SSRIs), which primarily increase serotonin levels, are generally safer than tricyclic antidepressants (TCAs) and show promising-though not definitive-results, especially when combined with mood stabilizers. Other newer-generation antidepressants may also have potential for the treatment of bipolar depression. The heterogeneity of mood disorders poses a significant challenge in the diagnosis of BD, which is often ambiguous and complex. The natural mood fluctuations associated with BD, in conjunction with the frequent comorbidities such as anxiety, render the treatment of this condition particularly challenging, particularly in the context of antidepressant therapy. While clinical trials are conducted with the utmost rigor, they frequently fail to account for the intricacies of the real-world context due to the strict inclusion criteria. The identification of predictors of effective antidepressant use, such as symptom severity and comorbid conditions, has the potential to enhance treatment outcomes. Future research should aim to identify individualized predictors and deepen understanding of mood disorder spectra to optimize antidepressant use in bipolar depression.
双相情感障碍（BD）的特征是出现躁狂/轻躁狂发作和抑郁发作，后者对发病率、死亡率和整体生活质量有重大影响。目前双相抑郁的治疗指南提供的治疗选择有限，只有少数几种获批疗法。尽管有这些限制，但约50%-60%被诊断为双相情感障碍的患者会被开抗抑郁药。然而，由于存在诱发躁狂、快速循环和症状不稳定的风险，这些药物的使用仍存在争议。本综述探讨了双相情感障碍各阶段的神经递质机制，重点关注单胺类，并评估不同抗抑郁药物治疗双相抑郁的疗效和安全性。去甲肾上腺素和多巴胺已被确定为与抑郁和躁狂两极相关的神经递质，推测在抑郁时减少，在躁狂时增加。有证据表明，血清素在抑郁阶段不足，但其失衡在躁狂时也会表现出来。主要提高血清素水平的选择性血清素再摄取抑制剂（SSRIs）通常比三环类抗抑郁药（TCAs）更安全，并且显示出有前景的——尽管不是决定性的——结果，尤其是与心境稳定剂联合使用时。其他新一代抗抑郁药可能也有治疗双相抑郁的潜力。心境障碍的异质性给双相情感障碍的诊断带来了重大挑战，其诊断往往模糊且复杂。与双相情感障碍相关的自然情绪波动，再加上焦虑等常见共病，使得这种疾病的治疗尤其具有挑战性，特别是在抗抑郁治疗的背景下。虽然临床试验进行得极其严格，但由于严格的纳入标准，它们常常无法考虑到现实世界情况的复杂性。确定有效使用抗抑郁药的预测因素，如症状严重程度和共病情况，有可能提高治疗效果。未来的研究应旨在确定个体化的预测因素，并加深对心境障碍谱的理解，以优化双相抑郁中抗抑郁药的使用。
