Horowitz Mark Abie, Taylor David
Prince of Wales Hospital, Sydney, NSW, Australia; Health and Environment Action Lab, London, UK.
Institute of Pharmaceutical Science, King's College London, London, UK.
Lancet Psychiatry. 2019 Jun;6(6):538-546. doi: 10.1016/S2215-0366(19)30032-X. Epub 2019 Mar 5.
All classes of drug that are prescribed to treat depression are associated with withdrawal syndromes. SSRI withdrawal syndrome occurs often and can be severe, and might compel patients to recommence their medication. Although the withdrawal syndrome can be differentiated from recurrence of the underlying disorder, it might also be mistaken for recurrence, leading to long-term unnecessary medication. Guidelines recommend short tapers, of between 2 weeks and 4 weeks, down to therapeutic minimum doses, or half-minimum doses, before complete cessation. Studies have shown that these tapers show minimal benefits over abrupt discontinuation, and are often not tolerated by patients. Tapers over a period of months and down to doses much lower than minimum therapeutic doses have shown greater success in reducing withdrawal symptoms. Other types of medication associated with withdrawal, such as benzodiazepenes, are tapered to reduce their biological effect at receptors by fixed amounts to minimise withdrawal symptoms. These dose reductions are done with exponential tapering programmes that reach very small doses. This method could have relevance for tapering of SSRIs. We examined the PET imaging data of serotonin transporter occupancy by SSRIs and found that hyperbolically reducing doses of SSRIs reduces their effect on serotonin transporter inhibition in a linear manner. We therefore suggest that SSRIs should be tapered hyperbolically and slowly to doses much lower than those of therapeutic minimums, in line with tapering regimens for other medications associated with withdrawal symptoms. Withdrawal symptoms will then be minimised.
所有用于治疗抑郁症的药物类别都与戒断综合征有关。选择性5-羟色胺再摄取抑制剂（SSRI）戒断综合征很常见，且可能很严重，这可能会迫使患者重新开始用药。虽然戒断综合征可以与潜在疾病的复发相区分，但它也可能被误诊为复发，从而导致长期不必要的药物治疗。指南建议在完全停药前，进行2至4周的短期减药，减至治疗最低剂量或最低剂量的一半。研究表明，与突然停药相比，这些减药方案的益处甚微，而且患者往往无法耐受。数月的减药并减至远低于最低治疗剂量的方案，在减轻戒断症状方面已显示出更大的成效。与戒断有关的其他类型药物，如苯二氮䓬类药物，通过按固定量逐渐减少剂量来降低其在受体上的生物学效应，以尽量减少戒断症状。这些剂量减少是通过指数减药方案进行的，最终减至非常小的剂量。这种方法可能与SSRI的减药有关。我们检查了SSRI对5-羟色胺转运体占有率的PET成像数据，发现以双曲线方式减少SSRI剂量会使其对5-羟色胺转运体抑制作用呈线性降低。因此，我们建议应按照与戒断症状相关的其他药物的减药方案，以双曲线方式缓慢减少SSRI剂量，减至远低于治疗最低剂量，这样戒断症状将被降至最低。
