Designing a Trial to Evaluate Potential Treatments for Apathy in Dementia: The Apathy in Dementia Methylphenidate Trial (ADMET)

Drye, Lea T.; Scherer, Roberta W.; Lanctôt, Krista L.; Rosenberg, Paul B.; Herrmann, Nathan; Bachman, David; Mintzer, Jacobo

doi:10.1016/j.jagp.2012.12.018

Cited by 17 publications

(38 citation statements)

References 67 publications

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“…15 Participants were recruited at Johns Hopkins Bayview Medical Center (Baltimore, Maryland), Medical University of South Carolina (Charleston, South Carolina), and University of Toronto Sunnybrook Health Sciences Centre (Toronto, Ontario, Canada) between June 2010 and October 2011. Ethics review boards at all 3 institutions approved study procedures.…”

Section: Methodsmentioning

confidence: 99%

Safety and Efficacy of Methylphenidate for Apathy in Alzheimer’s Disease

Rosenberg¹,

Lanctôt²,

Drye³

et al. 2013

J. Clin. Psychiatry

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167

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Objective In a recent crossover trial, methylphenidate treatment decreased apathy in Alzheimer's disease. We further assessed this finding in the Alzheimer's Disease Methylphenidate Trial (ADMET). Method Six-week, randomized, double-blind, placebo-controlled multicenter trial enrolling Alzheimer's disease participants (NINCDS-ADRDA criteria) with apathy assigned to methylphenidate 20 mg daily or placebo, conducted from June 2010 to December 2011. Primary outcomes were change in Apathy Evaluation Scale (AES) score and modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGI-C). Secondary outcomes included change in Neuropsychiatric Inventory (NPI) apathy score, Mini-Mental State Examination (MMSE) score, and safety. Results 60 participants were randomly assigned (29 methylphenidate, 31 placebo). At baseline, mean (SD) age = 76 (8) years, MMSE score = 20 (5), AES score = 51 (12), NPI total score = 16 (8), and 62% of the participants (n = 37) were female. After 6 weeks' treatment, mean (SD) change in AES score was −1.9 (1.5) for methylphenidate and 0.6 (1.4) for placebo (P = .23). Odds ratio for improvement in ADCS-CGI-C was 3.7 (95% CI, 1.3 to 10.8) (P = .02), with 21% of methylphenidate versus 3% of placebo rated as moderately or markedly improved. NPI apathy score improvement was 1.8 points (95% CI, 0.3 to 3.4) greater on methylphenidate than on placebo (P = .02). MMSE trended toward improvement on methylphenidate (P = .06). There were trends toward greater anxiety and weight loss > 2% in the methylphenidate-treated group. Conclusions Methylphenidate treatment of apathy in Alzheimer's disease was associated with significant improvement in 2 of 3 efficacy outcomes and a trend toward improved global cognition with minimal adverse events, supporting the safety and efficacy of methylphenidate treatment for apathy in Alzheimer's disease.

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Section: Methodsmentioning

confidence: 99%

Safety and Efficacy of Methylphenidate for Apathy in Alzheimer’s Disease

Rosenberg¹,

Lanctôt²,

Drye³

et al. 2013

J. Clin. Psychiatry

Self Cite

167

123

View full text Add to dashboard Cite

show abstract

“…Unfortunately, few controlled trials target treatment of apathy in AD. One recent randomized placebo-controlled trial of methylphenidate for apathy in AD (ADMET) reported improvement in two out of three efficacy outcomes with a trend toward improved global cognition with minimal adverse events [ 81 - 83 ]. Few other uncontrolled trials, however, have also shown treatment effects with methylphenidate [ 84 , 85 ] and one with donepezil [ 86 ].…”

Section: Management Of Common Neuropsychiatric Syndromes In Alzheimermentioning

confidence: 99%

Principles and management of neuropsychiatric symptoms in Alzheimer’s dementia

2015

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Neuropsychiatric symptoms of Alzheimer’s disease (NPS-AD) are highly prevalent and lead to poor medical and functional outcomes. In spite of the burdensome nature of NPS-AD, we are continuing to refine the nosology and only beginning to understand the underlying pathophysiology. Cluster analyses have frequently identified three to five subsyndromes of NPS-AD: behavioral dysfunction (for example, agitation/aggressiveness), psychosis (for example, delusions and hallucinations), and mood disturbance (for example, depression or apathy). Recent neurobiological studies have used new neuroimaging techniques to elucidate behaviorally relevant circuits and networks associated with these subsyndromes. Several fronto-subcortical circuits, cortico-cortical networks, and neurotransmitter systems have been proposed as regions and mechanisms underlying NPS-AD. Common to most of these subsyndromes is the broad overlap of regions associated with the salience network (anterior cingulate and insula), mood regulation (amygdala), and motivated behavior (frontal cortex). Treatment strategies for dysregulated mood syndromes (depression and apathy) have primarily targeted serotonergic mechanisms with antidepressants or dopaminergic mechanisms with psychostimulants. Psychotic symptoms have largely been targeted with anti-psychotic medications despite controversial risk/benefit tradeoffs. Management of behavioral dyscontrol, including agitation and aggression in AD, has encompassed a wide range of psychoactive medications as well as non-pharmacological approaches. Developing rational therapeutic approaches for NPS-AD will require a firmer understanding of the underlying etiology in order to improve nosology as well as provide the empirical evidence necessary to overcome regulatory and funding challenges to further study these debilitating symptoms.

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“…Notwithstanding, there is a rapid increase of prescriptions for ADHD treatment as well as off-label and illicit use [146] of MPH and amphetamines as ''smart pills'' for healthy individuals and as weight loss agents [147,148]. Together with a potential extension of the indication toward ever more potential users-most recently prisoners [149] or Alzheimer patients [30,150]-the percentage of exposed subjects throughout all age classes is bound to increase significantly in the coming years.…”

Section: Discussionmentioning

confidence: 99%

“…Another reason underlying the increased prescription rate is misuse of stimulants for cognitive enhancement/ neuroenhancement [28][29][30]. MPH is also off-label or illicitly used as a weight loss agent [12].…”

Section: Introductionmentioning

confidence: 99%

Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?

Antel

Albayrak

Heusch³

et al. 2014

Eur Arch Psychiatry Clin Neurosci

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With the recent approval of methylphenidate (MPH) for treating attention-deficit/hyperactivity disorder (ADHD) in adults, the number of patients exposed will increase tremendously. The ongoing debate on the cardiovascular safety of MPH has triggered two large retrospective cohort studies in children and adolescents as well as in young to middle-aged adults. These studies looked into serious cardiovascular events (sudden cardiac death, acute myocardial infarction and stroke) as primary endpoints and concluded that MPH was safe after a mean duration of 2.1 years of follow-up in children and adolescents and mean duration of 0.33 years of current use in adults. The results are encouraging with respect to the short- and medium-term use of MPH. Without the inherent limitations of retrospective cohort studies, a prospective randomized, double-blind, placebo-controlled, multicenter trial in individuals stratified for cardiovascular risk factors would allow for an optimized risk assessment. With many millions of patients treated per year and drawing parallels to the lately discovered risks of sibutramine, another sympathomimetic with an overlapping mode of action and similar side effects on heart rate and blood pressure, we hypothesize that such a trial might be a dedicated risk mitigation strategy for public health. A critical assessment of cardiovascular side effects of MPH appears particularly warranted, because ADHD is associated with obesity, smoking and poor health in general. We summarize recent findings with the focus on cardiovascular risks of MPH in humans; we additionally analyze the limited number of rodent studies that have addressed cardiovascular risks of MPH.

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Designing a Trial to Evaluate Potential Treatments for Apathy in Dementia: The Apathy in Dementia Methylphenidate Trial (ADMET)

Cited by 17 publications

References 67 publications

Safety and Efficacy of Methylphenidate for Apathy in Alzheimer’s Disease

Safety and Efficacy of Methylphenidate for Apathy in Alzheimer’s Disease

Principles and management of neuropsychiatric symptoms in Alzheimer’s dementia

Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?

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