Single dose of methylphenidate improves cognitive performance in multiple sclerosis patients with impaired attention process
Introduction
Growing awareness and accumulating data regarding cognitive impairment and its progression in multiple sclerosis (MS) patients has gained essential importance in neurological research in the last decade. Cognitive impairments occur in up to 65% of MS patients along the disease course [1]. Moreover, in more than 50% of MS patients in whom no cognitive disturbances are found on routine neurological examination, cognitive impairments can be elicited using sensitive and disease specific neuropsychological tests [2]. In up to 60% of patients with short disease duration of less than two years, discrete impairment of cognitive function was found on standard neuropsychological testing though without impact on activities of daily living [3]. Even in patients evaluated within one month from the onset of neurological symptoms suggestive of MS, verbal abilities and attention span were found to be affected in 43.3% and 41.8%, respectively [4]. Similarly, it was demonstrated that the attention dysfunction worsened when the cognitive load was high and when controlled information processing was required [5]. This high rate of attention impairment found in MS patients early in the disease process has a significant impact on patient's quality of life and activities of daily living, as attention is one of the most fundamental cognitive functions which is a requisite step towards conscious perception.
Methylphenidate is a psychostimulant that facilitates the action of dopamine and norepinephrine via inhibition of reuptake, facilitation of release into the synaptic cleft, and inhibition of the catabolic activity of monoamine oxidase [6]. Methylphenidate is known to be highly effective in alleviating inattentiveness, impulsivity and hyperactivity characterizing attention-deficit hyperactivity disorder (ADHD) [7]. The responses of normal children and adults to methylphenidate as well as subjects with ADHD are qualitatively similar and include reduction in activity level and impulsivity, enhancement of attention-related processes including focused attention [8], increased allocation of attention to a primary task in a divided attention paradigm [9], and reduction in errors of omission and commission on specific tasks requiring selective and sustained attention [10]. Moreover, methylphenidate proved to improve attention, memory, mood/behavioral ratings, and psychomotor skills in patients with traumatic brain injury, [11] and brain tumor [12].
In the current preliminary study we investigated whether a single dose of methylphenidate could improve attention and information processing in MS patients. We have chosen to use the paced auditory serial addition test (PASAT) as it has been found as a good instrument to evaluate cognitive impairment in MS patients [13]. The test requires several cognitive domains including sustained attention, processing speed, mental arithmetic, and working memory, [14] and thus is preferred to pinpoint changes related to the use of methylphenidate as a cognitive stimulant.
Section snippets
Study design
Double blind, placebo controlled. Patients and medical staff were blinded to the study drug which was randomly administered once, as a single tablet containing 10 mg of methylphenidate or placebo. The Sheba IRB committee and Israeli Ministry of Health approved the study.
Subjects
Patients with MS followed in our clinic were assessed by the comprehensive Neuropsychological Screening Battery for Multiple Sclerosis (NSBMS) [1] as a routine cognitive follow-up. Inclusion criteria for participation in the
Results
Twenty-six relapsing–remitting MS patients (20 females, 6 males), mean age 37.2 ± 10.6 years, mean disease duration 11.0 ± 7.4 years, and mean EDSS 3.5 ± 2.4 were included in the study. All were treated with interferon beta 1-a immunomodulating drug treatments, either Avonex or Rebif, for a period of more than 6 months.
Randomly, 14 patients received methylphenidate and 12 patients were given placebo. Baseline demographic and clinical variables including age, education, disease duration, and
Discussion
Methylphenidate is known to act on the presynaptic nerve endings and to restrain the reabsorption of serotonin and noradrenaline as well as it increases the secretion of dopamine [6]. Accordingly, its efficacy for improving attention and memory in patients with ADHD, traumatic brain injury, or brain tumors has been established [7], [11], [12].
Methylphenidate has been reported to improve tasks of working memory and divided attention in more than 50% of studies. Variability of the findings across
References (21)
Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration
Behav Brain Res
(1998)- et al.
Cortical reorganization during PASAT task in MS patients with preserved working memory functions
NeuroImage
(2006) - et al.
Cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder
Neurosci Biobehav Rev
(2006) - et al.
Electrophysiological indices of information processing in methylphenidate responders
Biol Psychiatry
(1997) - et al.
Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction
Neurology
(1991) - et al.
Neuropsychological aspects of multiple sclerosis
Neuropsychol Rev
(1998) - et al.
Cognitive functions in recent-onset demyelinating diseases
Arch Neurol
(1986) - et al.
Cognitive impairment in probable multiple sclerosis
J Neurol Neurosurg Psychiatry
(2003) - et al.
Attention impairment in recently diagnosed multiple sclerosis
Eur J Neurol
(1998) - et al.
Neuronal mechanisms of action of amphetamine
Cited by (49)
Pharmacotherapy in multiple sclerosis-induced cognitive impairment: A systematic review and meta-analysis
2020, Multiple Sclerosis and Related DisordersCitation Excerpt :Similarly, some studies have demonstrated the non-significant impacts of CNS stimulants including modafinil, amphetamine sulfate, and pemoline on the ability of information processing (Geisler et al., 1996; Morrow et al., 2009; Moller et al., 2011; Ford-Johnson et al., 2016; Cameron and McMillan, 2017). However, other studies have shown that CNS stimulants possess possible positive cognitive effects, especially on information processing and memory (Harel et al., 2009; Ford-Johnson et al., 2016). In line with that, Morrow et al. indicated that amphetamine salts improved memory, attention and data operation in both in PASAT and SDMT tests (Morrow et al., 2013; Morrow and Rosehart, 2015).
Multiple Sclerosis
2020, Braddom's Physical Medicine and RehabilitationAdvanced Symptom Management in Multiple Sclerosis
2018, Neurologic ClinicsCitation Excerpt :Therefore, thus far Alzheimer disease medications have not shown significant benefit for patients with MS. In contrast, there are some supportive data for medications approved for ADHD/narcolepsy. The positive trials include lisdexamphetamine dimesylate,20 l-amphetamine,41 and methylphenidate (Ritalin).42 Improvements in cognition were not limited to increased processing speed, suggesting that these medications may have benefits beyond improving fatigue or alertness.
Multiple Sclerosis
2018, Braddom's Rehabilitation Care: A Clinical HandbookThe neurobiology of HIV and its impact on cognitive reserve: A review of cognitive interventions for an aging population
2016, Neurobiology of DiseaseCitation Excerpt :These findings differ from those of another study in which Hinkin et al. (2001) administered methylphenidate to 16 adults with HIV and found that those experiencing more depression and cognitive slowing at baseline experienced more improvements on cognitive tasks such as reaction time (Hinkin et al., 2001). Although longitudinal studies examining the cognitive effects of methyphenidate in adults with HIV are lacking, it has been shown to improve cognition in other populations including multiple sclerosis (Harel et al., 2009) and normal healthy adults (Tomasi et al., 2011). Other benefits of methylphenidate include its ability to decrease total cholesterol, low-density lipoprotein cholesterol, and triglycerides (Charach et al., 2009).
Treatment of progressive multiple sclerosis: What works, what does not, and what is needed
2015, The Lancet NeurologyCitation Excerpt :More promising results have, however, been obtained from putative cognitive-enhancing agents in studies that focused on specific cognitive domains in patients with multiple sclerosis who were defined as impaired at study entry. Benefits have been reported from randomised controlled trials with a single dose of methylphenidate,109 4 months of modafinil,110 and l-amphetamine either given over 4 weeks or as four single doses.52,53 What makes the l-amphetamine result more intriguing is that a drug that ostensibly targets attention was found to have more widespread effects that included improvements in both verbal and visuospatial memory.