Department of Psychiatry, Dalhousie University (Dalhousie Medicine New Brunswick), Saint John, NB, Canada.
J Affect Disord. 2011 Aug;132 Suppl 1:S14-20. doi: 10.1016/j.jad.2011.03.047. Epub 2011 May 15.
Patients who meet the criteria for a major depressive episode experience a constellation of symptoms, and different symptom configurations may reflect distinct underlying neurological disturbances. Similarly, the differing receptor profiles of the various antidepressants may explain relatively low remission rates and persistent symptoms even after remission. In particular, depressed patients frequently display altered circadian rhythms, sleep disturbances, and diurnal mood variation. Exploring treatments that can restore mood while having a positive impact on circadian rhythms and sleep would greatly improve the ability to treat this core features of depression.
The mechanisms of action of the various classes of antidepressants, their effects on sleep and issues beyond sleep, including sexual dysfunction, are explored, along with questions relating to adherence.
Unfortunately, persistent sleep problems are among the most difficult-to-treat residual symptoms of depression. Many of the currently available antidepressants have adverse effects on circadian processes, including sleep, and may actually worsen sleep problems. Tolerability is also an enduring issue; SSRI and SNRI antidepressants are associated with central nervous sysytem and gastrointestinal effects, sexual side effects and suicidality. Improved drug tolerability would not only minimize distressing adverse effects, but would also improve adherence, thus maximizing the chances of successful treatment.
The complexity of managing a major depressive episode is well illustrated by sleep disturbance and sexual dysfunction, two core symptoms of MDD that may also be caused or exacerbated by antidepressant therapy. Future antidepressants should alleviate symptoms without adversely affecting sleep or sexual function.
符合重性抑郁发作标准的患者会出现一系列症状，不同的症状组合可能反映出不同的潜在神经紊乱。同样，各种抗抑郁药的不同受体谱可能解释了即使在缓解后仍存在相对较低的缓解率和持续症状。特别是，抑郁患者经常表现出昼夜节律紊乱、睡眠障碍和日间情绪变化。探索能够在影响昼夜节律和睡眠的同时恢复情绪的治疗方法，将极大地提高治疗这种核心特征的能力。
探索了各种类别的抗抑郁药的作用机制，它们对睡眠和睡眠以外问题的影响，包括性功能障碍，以及与依从性相关的问题。
不幸的是，持续的睡眠问题是最难治疗的抑郁残留症状之一。许多现有的抗抑郁药对包括睡眠在内的昼夜节律过程有不良影响，实际上可能会使睡眠问题恶化。耐受性也是一个持久的问题；SSRI 和 SNRIs 类抗抑郁药与中枢神经系统和胃肠道作用、性功能障碍和自杀意念有关。提高药物耐受性不仅会最小化令人痛苦的不良反应，还会提高依从性，从而最大限度地提高成功治疗的机会。
睡眠障碍和性功能障碍这两个 MDD 的核心症状，可能是由抗抑郁治疗引起或加重的，说明了管理重性抑郁发作的复杂性。未来的抗抑郁药应该在不影响睡眠或性功能的情况下缓解症状。
