Does Modafinil Have Pro-cognitive Effects in Those With Residual Cognitive Impairment Despite Remitted Depression?
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Cognition
研究概览
简要总结
Cognitive difficulties such as indecisiveness or inability to concentrate are core symptoms of depression with up to 90% of untreated depressed individuals experiencing these symptoms. As many as half of those who remit from a major depressive episode continue to experience residual cognitive deficits, but these symptoms are frequently overlooked in clinical practice. This leads to persistent cognitive deficits which can cause reduced level of functioning and loss of productivity. As standard antidepressants have an inadequate impact on these residual cognitive symptoms, further treatment options are required. Modafinil is a wakefulness agent with evidence that it improves some domains in cognition such as memory in those whose non-cognitive depressive symptoms have been treated over a short term period. This medication may have favourable lasting effects on cognition, such as the ability to plan and execute tasks in those who receive modafinil for a longer time period. The aim of this study is to investigate whether modafinil can enhance cognition and have additional effects on functioning and work productivity in a sample of participants who were treated for depression but who continue to experience cognitive deficits.
详细描述
Background:
Major Depressive Disorder (MDD) is a chronic mental disorder with a lifetime prevalence of 5-20% (Kessler et al., 2003; Woo et al., 2016). While depressed mood and loss of interest in activities are core features of MDD, cognitive deficits such as indecisiveness and inattention are present and interfere with work and social functioning (McIntyre et al., 2013). These cognitive deficits frequently persist beyond remission from a Major Depressive Episode (MDE), with up to 94% of those impaired during an episode continuing to experience deficits after the episode (Bhalla et al., 2006), including deficits in attention, executive functioning, and psychomotor speed (Salagre et al., 2017). These residual cognitive symptoms often persist and are associated with poor functioning and loss of productivity (Lam et al., 2014).
In a systematic review examining MDD patients in remission, multiple regression analyses found that MDD predicted lower performance on measures of attention, processing speed, and cognitive flexibility relative to healthy controls (HCs; Hasselbalch et al., 2011). Further evidence for the presence of neuropsychological deficits in remitted MDD patients comes from a systematic review and meta-analysis that found the remitted MDD patient group had executive function and attentional deficits, while symptomatic patients exhibited executive function, attentional, and memory deficits (Roc et al., 2013).
Importantly, there are no medications with evidence to modify cognition in remitted depression. This suggests that in order to assist in the recovery of cognitive and functional abilities, additional novel treatment options are required.
There is considerable evidence that subjective and objective measures of cognition are not well correlated in MDD. This has informed the investigators' choice of separate subjective and objective measures for this study. In addition, cognitive disturbances affect psychosocial function and quality of life across several areas, and this necessitated measurement of quality of life. In this study, the investigators will use a computerized version of the Central Nervous System (CNS) Vital Signs Cognitive Battery, which will provide a Neurocognitive Index score (NCI). The NCI is a global measure of cognitive functioning, averaging the scores from 7 tests over 5 domains: composite memory, psychomotor speed, reaction time, complex attention, and cognitive flexibility.
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
25 participants will be randomly assigned to the modafinil treatment group, and 25 to the placebo group. The drug/placebo will be randomized and dispensed by the research pharmacy at St. Michael's Hospital. A research technician who is blind to the study will prepare the capsules and break the blind at the end of the study.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnostic and Statistical Manual (DSM)-5 criteria for past Major Depressive Episode within MDD, confirmed through Mini-International Neuropsychiatric Interview (MINI) diagnosis
- •Age between 18 and 55 years
- •Montgomery-Åsberg Depression Rating Scale < 7 (in remission)
- •Ability to read and understand English
- •Participant has been treated with an antidepressant for ≥ 6 months prior to enrolment
- •Participant agrees to remain on a stable antidepressant regimen for the duration of the trial (8 weeks)
- •Participant is currently experiencing cognitive deficits, as confirmed by an NCI >1 standard deviation below the mean on CNS Vital Signs cognitive battery
- •Women of child bearing potential must agree to use birth control for the duration of the study and 1 month following discontinuation of the study drug
排除标准
- •Pregnancy/lactation
- •Lifetime history of Bipolar I, II or psychosis; other comorbidities (e.g. Generalized Anxiety, Panic Disorder) may be allowed by clinician judgement
- •Subject has current clinical diagnosis of autism, dementia, intellectual disability, or mild cognitive impairment
- •Meets DSM-5 criteria for active Post-Traumatic Stress Disorder, confirmed through MINI diagnosis
- •Subject meets criteria for current personality disorder
- •Concomitant use of monoamine oxidase inhibitors and/or other psychotropic drugs including lithium, clomipramine, and triazolam
- •Recent (< 6 months) stimulant use, such as medications used for attention deficit hyperactivity disorder
- •Subject is taking antipsychotics
- •Subject is taking herbaceuticals (i.e. natural products that have psychoactive properties, such as St. John's wort)
- •Concomitant use of medications that may interact with modafinil, including warfarin and cyclosporine
- •Medical condition requiring immediate investigation or treatment
- •Recent (< 6 months)/current history of drug abuse/dependence (other than caffeine or nicotine)
- •Previous intolerance or failure to respond to an adequate trial of modafinil
- •Any past history of head injury or concussion, as confirmed by the Ohio State University Traumatic brain injury (TBI) Identification Short Form
- •Current suicidal ideation (MADRS Item 10 ≤2 or by clinician judgement)
- •History of coronary artery disease, recent (<1 year) myocardial infarction, or unstable angina
- •History of left ventricular hypertrophy, ischemic ECG changes, chest pain, arrhythmia, or clinically significant manifestations of mitral valve prolapse in association with use of CNS stimulants
- •Involvement in another treatment study during the time of the study
研究组 & 干预措施
Modafinil
Participants will be administered 100 mg modafinil tablets, that will be over-encapsulated, for one week. If the drug is well tolerated, the dosage will be increased to 200 mg for the remaining 7 weeks of the study. Capsules are taken daily in the morning.
干预措施: Modafinil (Drug)
Placebo
Participants will be administered 100 mg placebo capsule. This capsule will have all the same ingredients as the modafinil tablets, minus the active ingredient. After 1 week, participants' dosage will be increased to 200 mg for the remaining 7 weeks of the study. Capsules are taken daily in the morning.
干预措施: Placebo (Drug)
结局指标
主要结局
Cognition
时间窗: 8 weeks
Cognition will be measured using a Neurocognitive Index, which will be calculated using the CNS Vital Signs Neurocognitive Battery (a computer program). The domains tested within the cognitive battery include composite memory, psychomotor speed, reaction time, complex attention, cognitive flexibility, and processing speed. The Neurocognitive Index is based on a composite, average score of the scores on these 6 domains. From the Neurocognitive Index score, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 85.
次要结局
- Composite Memory(8 weeks)
- Work Productivity(8 weeks)
- Reaction Time(8 weeks)
- Subjective Cognitive Improvement(8 weeks)
- Motivation and Energy(8 weeks)
- Cognitive Flexibility(8 weeks)
- Psychomotor Speed(8 weeks)
- Complex Attention(8 weeks)
- Processing Speed(8 weeks)
- Functional Disability(8 weeks)
研究者
Shane McInerney
Staff Psychiatrist
Unity Health Toronto