Minocycline As Adjunctive Treatment for Treatment Resistant Depression: a Double Blind, Placebo-controlled, Randomized Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Depressive symptoms
研究概览
简要总结
Major depressive disorder (MDD) is a leading cause of disability worldwide. Up to 50% of patients experience treatment resistant depression (TRD), which accounts for a vast majority of disease burden. Current medications for TRD have limited efficacy and can be associated with intolerable side effects. Therefore, there is a need for finding new treatment targets. Accumulating evidence suggests some patients with MDD including those with TRD, display brain inflammation. Thus, patients with TRD may benefit from medications that can reduce this inflammation. Minocycline is an antibiotic which can cross the blood-brain barrier and has effects on several systems implicated in depression. The principal investigator led the first pilot study of minocycline as an add-on treatment in TRD demonstrating that it led to a significant reduction in depressive symptoms compared to placebo and these findings require replication in a larger sample to confirm the efficacy and tolerability of this treatment approach.
This study is a 12 week, double-blind, placebo-controlled trial of minocycline as add-on treatment for patients suffering from a major depressive episode who have failed to respond to antidepressant treatment, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5) and the Antidepressant Treatment History Form (ATHF) at screening. After screening and randomization to the two parallel arms of the trial, 50 patients will receive minocycline added to treatment as usual (TAU) and 50 patients will receive placebo added to TAU. Clinical assessment will include the Hamilton Depression Rating Scale (HRSD-17), Clinical Global Impression scale (CGI), World Health Organization Quality of Life Short Form (WHOQOL-BREF), and Generalized Anxiety Disorder scale (GAD-7), administered at each study visit (baseline, week 2, 6, and 12). Side effects checklists will be undertaken at each visit. Minocycline will be started at 100 mg once daily and will be increased to 100 mg twice daily at two weeks. Secondary outcomes include inflammatory biomarkers measured at baseline, weeks 6 and 12.
This trial will provide further evidence of minocycline's efficacy and acceptability as a treatment option for patients with TRD and provide insights into its mechanism of action.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patients, their families, referring clinicians, lab workers and research assistants carrying out assessments will be concealed from allocation. Once randomized, pharmacy at the Centre for Addiction and Mental Health (CAMH) will be informed by email and deliver medication to the patient. An independent study psychiatrist will manage any clinical concerns and will be blind to treatment allocation. To assess the integrity of blinding procedures, participants and independent raters will be asked to complete a conventional guess form asking whether they believe participants received Minocycline or placebo as a treatment after the final ratings have been completed.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Outpatients
- •Voluntary and competent to consent to treatment
- •DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the SCID-5
- •Male or female aged between 18-80
- •Total score > 3 on ATHF
- •Baseline HRSD-17 score > 14
- •Able to adhere to study schedule
- •If female of childbearing potential, currently on a medically acceptable form of birth control (oral contraceptives, contraceptive injections, IUD, contraceptive patch, male partner sterilization, abstinence, or barrier methods plus spermicide)
- •Currently taking one of the following standard antidepressants: Escitalopram, Citalopram, Sertraline, Venlafaxine, Duloxetine, Mirtazapine or Bupropion
- •Been on same dose of all psychotropic medications for > 4 weeks prior to enrolment
排除标准
- •DSM-5 substance use disorder within past 3 months, moderate or severe, based on SCID-5
- •Concomitant major unstable medical illness
- •Pregnancy or intent to become pregnant during study period
- •DSM-5 diagnosis of psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) within last year
- •DSM-5 diagnosis of borderline personality disorder (BPD)
- •Possible or probable dementia
- •Prior or current intolerance or contraindication to tetracyclines
- •Abnormal readings in hematology, liver, or renal function tests
- •Have Myasthenia Gravis
- •Concomitant treatment with anticoagulants, diuretics, retinoids, ergot alkaloids, antacids containing aluminium/calcium/magnesium, bismuth and zinc salts, or quinapril
研究组 & 干预措施
Active
Minocycline will start at an oral dose of 100mg daily and will be increased after one week to 100mg twice daily.
干预措施: Minocycline (Drug)
Placebo
Placebo capsules will start at one capsule daily, and will be increased after one week to one capsule twice daily
干预措施: Minocycline (Drug)
结局指标
主要结局
Depressive symptoms
时间窗: 12 weeks
Changes from baseline to week 12 on the 17-item Hamilton Rating Scale for Depression (HRSD-17).
次要结局
- Response rate(12 weeks)
- Remission rate(12 weeks)
- Self-reported perception of quality of life(12 weeks)
- Clinician-rated illness severity(12 weeks)
- Anxiety symptoms(12 weeks)
研究者
Ishrat Husain
Clinician Scientist
Centre for Addiction and Mental Health