Wiegand Michael H
Department of Psychiatry and Psychotherapy, Sleep Disorders Center, Technical University of Munich, Munich, Germany.
Drugs. 2008;68(17):2411-7. doi: 10.2165/0003495-200868170-00001.
The popularity of antidepressants in the treatment of insomnia is not supported by a large amount of convincing data, but rather by opinions and beliefs of the prescribing physicians on the advantages of these agents compared with drugs acting on the benzodiazepine receptor or other drugs used for the treatment of insomnia. The existing data do not allow for clear-cut, evidence-based recommendations concerning the use of antidepressants in insomnia. Our conclusions result from a few short-term studies on single agents, clinical experience and inferences from knowledge on the effect of antidepressants in other indications. At present, prescribing antidepressants for short-term treatment of insomnia can be useful if there is some amount of concomitant depressive symptomology or a history of depression, raising the impression that the present insomnia may be a prodromal sign for a new depressive episode. In all other cases, benzodiazepine receptor agonists, especially the nonbenzodiazepines among them (the so-called 'z drugs') should be the drugs of choice. For long-term treatment, antidepressants are among the pharmacological options, in addition to other groups of psychotropics. Off-label use of antidepressants may be considered for chronic insomnia if there is a concomitant depressive symptomalogy (which is not so pronounced that an antidepressant treatment with adequate higher doses would be required) and if there is no specific indication for one of the other groups of psychotropics (e.g. dementia-related nocturnal agitation, in which case an antipsychotic would be preferred, or circadian problems, in which case melatonin or a melatonin agonist would be favoured). If antidepressants are used to treat insomnia, sedating ones should be preferred over activating agents such as serotonin reuptake inhibitors. In general, drugs lacking strong cholinergic activity should be preferred. Drugs blocking serotonin 5-HT2A or 5-HT2C receptors should be preferred over those whose sedative property is caused by histamine receptor blockade only. The dose should be as low as possible (e.g. as an initial dose: doxepin 25 mg, mirtazapine 15 mg, trazodone 50 mg, trimipramine 25 mg). Regarding the lack of substantial data allowing for evidence-based recommendations, we are facing a clear need for well designed, long-term, comparative studies to further define the role of antidepressants versus other agents in the management of insomnia.
抗抑郁药在治疗失眠方面的广泛应用并非基于大量令人信服的数据，而是基于开处方医生对这些药物相对于作用于苯二氮䓬受体的药物或其他用于治疗失眠的药物的优势的看法和信念。现有数据无法就抗抑郁药在失眠治疗中的使用提出明确的、基于证据的建议。我们的结论源于对单一药物的一些短期研究、临床经验以及从抗抑郁药在其他适应症中的作用知识得出的推论。目前，如果存在一定程度的伴随抑郁症状或有抑郁病史，从而使人认为当前的失眠可能是新的抑郁发作的前驱症状，那么开抗抑郁药用于短期治疗失眠可能是有用的。在所有其他情况下，苯二氮䓬受体激动剂，尤其是其中的非苯二氮䓬类药物（所谓的“Z 类药物”）应作为首选药物。对于长期治疗，除其他几类精神药物外，抗抑郁药也是药理学选择之一。如果存在伴随的抑郁症状（但不严重到需要使用足够高剂量的抗抑郁药治疗），并且没有其他几类精神药物的特定适应症（例如与痴呆相关的夜间躁动，在这种情况下首选抗精神病药物；或昼夜节律问题，在这种情况下首选褪黑素或褪黑素激动剂），则可考虑将抗抑郁药用于慢性失眠的标签外使用。如果使用抗抑郁药治疗失眠，应首选具有镇静作用的药物，而不是如 5-羟色胺再摄取抑制剂等具有激活作用的药物。一般来说，应首选缺乏强烈胆碱能活性的药物。与仅通过组胺受体阻滞产生镇静作用的药物相比，应首选阻断 5-羟色胺 5-HT2A 或 5-HT2C 受体的药物。剂量应尽可能低（例如作为初始剂量：多塞平 25 毫克、米氮平 15 毫克、曲唑酮 50 毫克、三甲丙咪嗪 25 毫克）。鉴于缺乏大量数据以提出基于证据的建议，我们显然需要设计良好的长期比较研究，以进一步确定抗抑郁药与其他药物在失眠管理中的作用。
