A Randomised Pragmatic Trial Comparing the Clinical and Cost Effectiveness of Lithium and Quetiapine Augmentation in Treatment Resistant Depression
试验速览
- 阶段
- 4 期
- 入组人数
- 276
- 试验地点
- 1
- 主要终点
- Longitudinal depressive symptom severity
研究概览
简要总结
LQD is a multicentre randomised clinical trial comparing the clinical and cost effectiveness of lithium versus quetiapine when used as add-on therapies to antidepressant medication for patients with treatment resistant depression. The Lithium versus Quetiapine in Depression (LQD) study will assess patients over 12 months to establish which (if any) treatment is more likely to improve TRD over a long duration of time. Professor Anthony Cleare is the Chief Investigator and recruitment began in November 2016.
详细描述
This 12 month parallel group, multi-centre, patient randomised, pragmatic, open label trial is comparing the clinical and cost-effectiveness of the decision to prescribe lithium versus quetiapine add-on treatment to antidepressant medication. There will be two parallel groups: 1) Quetiapine add-on to existing antidepressant medication; 2) Lithium add-on to existing antidepressant medication. 276 patients will be randomised 1:1 at baseline to the decision to prescribe either lithium or quetiapine, and treatment will then be undertaken by clinicians on a real world basis. All patients, regardless of their treatment status, will be followed up in the trial for one year. This is a superiority design whereby we hypothesise that quetiapine will be superior to lithium in terms of time to treatment discontinuation and average symptom burden (QIDS-SR) over 12 months.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Under the care of a GP and/or adult mental health services
- •Current episode of depression meeting DSM-5 criteria for major depressive disorder (MDD) - single or recurrent episode 3.17-item HAM-D score ≥ 14 - this cut-off reflects a pragmatic minimum severity of depression as also chosen in comparable studies such as STAR*D (Rush et al 2006, Trivedi et al 2006)
- •4.Any gender and aged 18 years or over 5.Meet criteria for treatment resistant depression (Fekadu et al., 2009a; Cleare et al., 2015): current episode has not responded to at least two antidepressants given for at least 6 weeks at minimum therapeutic dose defined as fluoxetine ≥20mg/day, paroxetine ≥20mg/day, sertraline ≥50mg/day, citalopram ≥20mg/day, escitalopram ≥10mg/day, venlafaxine ≥75mg/day, duloxetine ≥60 mg/day, mirtazapine ≥15mg/day, tricyclic antidepressant ≥125mg/day, and dosage as guided by the national Maudsley Prescribing Guidelines or BNF for any other antidepressant. Please note, relapse whilst on an antidepressant also counts as a failed treatment trial 6.Current antidepressant treatment has remained unchanged and at, or above, a therapeutic dose for ≥6 weeks 7.Provision of written, informed consent.
排除标准
- •Diagnosis of bipolar disorder (defined as meeting DSM-5 criteria for bipolar 1 or bipolar 2) on the MINI 7.0 (as recommended treatments are different for bipolar depression)
- •Diagnosis of current psychosis (as recommended treatments are different for current psychosis - antidepressants plus antipsychotics is the first-line treatment recommendation (NiCE, 2009; Cleare et al., 2015)
- •Adequate use of lithium or quetiapine during the current episode. An adequate dose of lithium is defined as the patient taking lithium for at least 4 weeks at an adequate dose (leading to a documented plasma concentration of >0.4mmol/L) and for quetiapine, prescription in the range of 150-300mg/d for 4 weeks or longer. Or, if the patient has taken an inadequate dose of lithium or quetiapine in the current episode, the patient and clinician are not willing to re-prescribe/take the medication.
- •Ongoing use of another atypical antipsychotic (discontinuation will be required before study entry i.e. any time prior to randomisation)
- •Known contraindication to use of either lithium or quetiapine: known hypersensitivity of lithium or quetiapine or any of their excipients; severe renal insufficiency / impairment; untreated hypothyroidism; severe cardiac disease / insufficiency; low sodium levels e.g. dehydrated patients or those on low sodium diets; Addison's disease; Brugada syndrome or family history of Brugada syndrome; the rare hereditary inborn errors of metabolism galactosaemia, the Lapp lactase deficiency or glucose-galactose malabsorption; concomitant administration of cytochrome P450 3A4 inhibitors; or congenital QT prolongation.
- •We will not recruit any individual who is currently participating in a clinical trial of an investigational medical product (CTIMP).
- •Insufficient degree of comprehension or attention to be able to engage in trial procedures.
- •We will exclude women who are pregnant, actively trying for pregnancy, or currently breastfeeding. This will be based on verbal report of the subject. Otherwise the management will be as appropriate according to standard clinical practice within the context of a pragmatic, open trial, for example adequate contraceptive precautions decided on the clinical judgement of the prescriber.
研究组 & 干预措施
Lithium
Lithium will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment.
干预措施: Lithium (Drug)
Quetiapine
Quetiapine will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment.
干预措施: Quetiapine (Drug)
结局指标
主要结局
Longitudinal depressive symptom severity
时间窗: 52 weeks
QIDS-SR
Difference in time to all-cause treatment discontinuation
时间窗: 12 months
The difference in the time at which patients stop taking the medication for any reason between the two treatment arms.
次要结局
- Change in clinician rated depression severity(From baseline to weeks 8 and 52)
- Response rates(8 weeks and 52 weeks)
- Remission rates(8 and 52 weeks)
- Health related quality of life(Measured at 8 and 52 weeks)
- Social functioning(Measured at baseline, 8 and 52 weeks)
- Adherence to treatment(Measured at weeks 8 and 52)
- Change in weight in kilograms(Measured at 8 and 52 weeks)
- Change in diastolic blood pressure(Change from baseline to 8 and 52 weeks)
- Change in systolic blood pressure(Change from baseline to 8 and 52 weeks)
- Time to uptake of a new intervention (pharmacological or non-pharmalogical)(12 months)
- Time to initiation of treatment(Up to 12 months)
- CGI Global Improvement(Measured at 8 and 52 weeks)
- Side effects(Measured at 8 and 52 weeks)
- Serious Adverse Events(52 weeks)