Canadian College of Naturopathic Medicine, Canada.
Canadian College of Naturopathic Medicine, Canada; Australian Research Centre in Complementary and Integrative Medicine, University of Technology, Sydney, Australia.
Complement Ther Med. 2018 Feb;36:38-45. doi: 10.1016/j.ctim.2017.09.011. Epub 2017 Nov 23.
Many patients with depression fail to achieve remission after several consecutive treatments. Vitamin D deficiency is prevalent and new research suggests that it may have an impact on mood, primarily through an effect on neurotransmitters. Numerous observational studies suggest a relationship between low levels of vitamin D and increased incidence and severity of mood disorders. A small number of pilot studies have been undertaken but lack rigorous methodology required to draw conclusions about a clinical role for this nutrient in treatment resistant depression.
This study was designed as a randomized, double-blind, placebo controlled intervention study administering a weekly (bolus) dose of 28 000IU of Vitamin D3 or placebo to 125 patients with non-remitted depression adjunct to current antidepressant medication. Patients were followed weekly for eight weeks plus a one month follow up. Outcomes measured included depression severity, serum vitamin D levels and safety. Due to slow recruitment during the first season, amendments were made. These included extending the age range to 18-75 and removing the requirement for failing to respond to one pharmacologic antidepressant agent. The protocol was amended to reduce the burden on participants by changing the in-office visits to bi-weekly. Three additional tertiary psychiatric clinics were also added as trial sites.
Over three recruitment period years (fall/winter), a total of 148 participants completed screening, 24 (16.2%) of whom qualified to participate in the study. Use of too many or no psychiatric medications, comorbid exclusionary psychiatric conditions, current use of a vitamin D supplement, and lack of participant compensation were the predominant reasons for ineligibility or unwillingness to participate. 9 participants were successfully enrolled in the study, 7 (77.8%) of whom completed the trial as per the protocol. After the third season, futility was declared based on inability to enroll participants. The sample size of enrolled participants (7/125, 5.6%) lacks power to conduct a full assessment of findings.
High accessibility of vitamin D, as well as a growing lack of equipoise in patients and clinicians about the potential ubiquitous benefits of vitamin D for Canadians, not just for mood disorders, resulted in a large proportion of ineligible potential participants. Limited funding provided to studies on natural health products hampered recruitment. The labile and fluctuating nature of non-remitted depression as well as frequent co-morbid conditions creates additional challenges for conducting trials in this population. Future studies assessing vitamin D in depression should consider our experiences in design and conduct of research. Innovations in clinical trial design such as preference trials or accepting patients already using vitamin D but not achieving an optimal target value are potential solutions to some of these challenges.
许多抑郁症患者在连续多次治疗后仍未痊愈。维生素 D 缺乏症很常见，新的研究表明，它可能会通过影响神经递质对情绪产生影响。大量观察性研究表明，维生素 D 水平低与情绪障碍的发生率和严重程度增加之间存在关系。少数试点研究已经进行，但缺乏严谨的方法学来得出关于这种营养素在治疗抵抗性抑郁症中的临床作用的结论。
本研究设计为一项随机、双盲、安慰剂对照的干预研究，对 125 名未缓解的抑郁症患者在当前抗抑郁药物治疗的基础上，每周（大剂量）给予 28000IU 的维生素 D3 或安慰剂。患者每周随访 8 周，并进行 1 个月的随访。测量的结果包括抑郁严重程度、血清维生素 D 水平和安全性。由于第一个季节招募缓慢，因此进行了修订。这些修订包括将年龄范围扩大到 18-75 岁，并取消了对一种药物治疗抗抑郁药物反应失败的要求。该方案通过将门诊就诊次数改为每两周一次，从而减少了参与者的负担。还增加了三个额外的三级精神病诊所作为试验地点。
在三个招募期（秋季/冬季）中，共有 148 名参与者完成了筛选，其中 24 名（16.2%）符合参与研究的条件。使用过多或没有精神科药物、合并排除精神科疾病、当前使用维生素 D 补充剂以及缺乏参与者补偿是不合格或不愿参与的主要原因。9 名参与者成功入组研究，其中 7 名（77.8%）按方案完成了试验。第三个季节后，由于无法招募参与者，宣告无效。入组参与者的样本量（7/125，5.6%）缺乏充分评估发现的能力。
维生素 D 的高可及性，以及患者和临床医生对维生素 D 对加拿大人的潜在普遍益处（不仅限于情绪障碍）的共识不断减少，导致很大一部分潜在参与者不合格。对天然保健品研究的有限资金限制了招募。非缓解性抑郁症的不稳定和波动性质以及频繁合并症给该人群的试验带来了额外的挑战。未来评估抑郁症中维生素 D 的研究应考虑我们在研究设计和实施方面的经验。临床试验设计的创新，如偏好试验或接受已经使用维生素 D 但未达到最佳目标值的患者，是解决其中一些挑战的潜在解决方案。
