Cognition and Fatigue in Multiple Sclerosis: Potential Effects of Medications with Central Nervous System Activity
Oken, Barry S., Flegal, Kristin, Zajdel, Daniel, Kishiyama, Shirley S., Lovera, Jesus, Bagert, Bridget, Bourdette, Dennis N., Journal of Rehabilitation Research & Development
Abstract--To evaluate the potential effects of medications with central nervous system (CNS) activity on cognitive function and fatigue in multiple sclerosis (MS), we performed a retrospective analysis of medication use among 70 subjects with MS who were participating in a clinical trial for evaluation of the effects of yoga and exercise programs on cognition and fatigue. Among these MS subjects, 74% were taking at least one potentially CNS-active medication. These 70 subjects were divided into two groups: those taking at least one CNS-active medication (n = 52) and those not on any medications with potential CNS activity (n = 18). We compared assessments of cognitive function and fatigue using an analysis of covariance. MS subjects on CNS-active medication had greater impairment on measures of processing speed, sustained attention, and fatigue than those not on these medications. While these findings do not establish a causal relationship between medication use and cognitive impairment and fatigue, the data indicate that researchers need to control for use of CNS-active medications when conducting studies of cognitive impairment and fatigue in MS subjects.
Key words: alertness, attention, attentional shifting, central nervous system agents, cognition, divided attention, fatigue, multiple sclerosis, processing speed, reaction time, sustained attention.
Many cognitive function changes occur with multiple sclerosis (MS) [1-2]. These cognitive changes may involve almost any area of cognition, although deficits in attention, including speed of processing, are particularly common . People with attentional system deficits from MS, or other conditions such as frontal lobe lesions or aging, may have memory deficits secondary to the attentional problems [3-5]. These attentional systems, along with the interrelated alertness systems, are more affected by drugs than other aspects of cognitive function. This is especially true for drugs with direct effects on neurotransmitters that are involved in the relatively nonspecific cortical projection systems (acetylcholine, norepinephrine, dopamine, serotonin, and histamine) or widely distributed cortical neurotransmitters (gamma-aminobutyric acid). Thus, a confounding issue in the study of cognition in MS is the frequent presence of medications with central nervous system (CNS) activity.
Many CNS-active drugs are known to affect cognitive function [6-7]. People who may already experience some cognitive impairment such as MS patients, as well as elderly people and patients with traumatic brain injury, are at higher risk than most people for additional cognitive dysfunction from medications . Among these drugs with negative effects on cognitive function, antiepileptic drugs (AEDs) may be the most clinically studied. All AEDs have some negative effects on cognitive function as assessed by blinded placebo-controlled studies in healthy subjects, although some relative differences exist among the AEDs in the magnitude of these effects . One point of potential relevance to MS is that subjective complaints of cognitive dysfunction from AEDs often exceed deficits identified by more formal neuropsychological testing, although cognitive tests sensitive to the effects of AEDs may require greater effort [9-10]. Many other drugs used by people with MS may negatively affect cognitive function as assessed by controlled trials in healthy control subjects, patient groups, or animals. This list includes tricyclic antidepressants, anticholinergics, first generation antihistamines, baclofen, beta-blockers, amantadine, selective serotonin reuptake inhibitors (SSRIs), and benzodiazepines [6-7,11-21]. On the other hand, methylphenidate and related drugs (modafinil) improve some cognitive functions in healthy subjects [11,22-23].
In many studies of MS and cognition, including some clinical trials, relatively little attention has been paid to the issue of CNS-active drugs . …