The effects of l-amphetamine sulfate on cognition in MS patients: results of a randomized controlled trial

Abstract

Defects in processing speed and memory are common in multiple sclerosis (MS) patients. In other populations, amphetamines have been shown to enhance cognition, but their use is limited by adverse behavioral effects. The L-isomer may have equivalent cognition enhancement with less adverse effects due to decreased potency in subcortical areas. The aim of this study was to assess the safety and efficacy of L-amphetamine sulfate in the treatment of cognitive dysfunction in MS. This was a 2:1 randomized, placebo-controlled, double-blind trial, involving 33 MS clinics across the USA. One hundred and fifty-one clinically definite MS patients with documented cognitive dysfunction who were relapse free for >or=90 days, with an Expanded Disability Status Scale (EDSS) <or=6.5, and with no other medical/psychiatric condition that may cause psychological dysfunction were randomized to 30 mg of oral L-amphetamine sulfate or placebo for 29 days, including a dose escalation period. A history of cardiac disease, uncontrolled hypertension or electrocardiograph abnormalities resulted in exclusion. The primary outcomes were the Subject Global Assessment of Change and Symbol Digit Modalities Test (SDMT). Secondary outcomes were the results from the California Verbal Learning Test, second edition (CVLT2), Brief Visual Memory Test-Revised (BVMTR), and Paced Auditory Serial Addition Test (PASAT). One hundred and thirty-six subjects completed the study. No differences were found at baseline in demographics or in the results of the neuropsychological tests. After treatment, the active group performed significantly better for total learning (P = 0.041) and delayed recall (P < 0.01) on the BVMTR, and for delayed recall (P = 0.012) on the CVLT2. Five patients (four from the treatment group, one placebo) withdrew due to intolerable adverse events. L-amphetamine sulfate was associated with improved learning and memory and was well tolerated in this study. However, because the positive findings were observed on secondary outcome measures, the study requires replication before L: -amphetamine sulfate can be recommended for the treatment of cognitive impairment in MS.

The Need for Screening, Assessment, and Treatment for Cognitive Dysfunction in Multiple Sclerosis

“…Initially there were encouraging data showing that l-amphetamine 13 and donepezil 14 can be effective for improving processing speed and memory defects, respectively. 15,16 Unfortunately, these studies were not replicated in subsequent research. Despite the lack of evidence, 58% of MS health-care providers in the survey indicated that they prescribe a variety of medications to improve cognitive symptoms in MS.…”

Psychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation

“…By contrast, an earlier study found either no difference or minor impairments on a range of 202 cognitive tasks (e.g., symbol copy, digit symbol) when those with schizophrenia were administered D-amphetamine (10 or 20 mg; Kornetsky, 1976). L-Amphetamine, administered orally in increasing doses throughout a 29-day period (5 mg for days 1-7, 15 mg for days 8-14, and 30 mg for days 15-29), enhanced verbal and spatial memory in cognitively impaired multiple sclerosis patients (Morrow et al, 2009). D-Amphetamine, compared with placebo in a double-blind study, enhanced recovery from aphasia in stroke patients who were administered 10 mg of drug 30 minutes before speech therapy for 1 week (Walker-Batson et al, 2001).…”

Disease modifying treatments and symptomatic drugs for cognitive impairment in multiple sclerosis: where do we stand?

“…In a pilot double-blind, placebo-controlled study involving 19 MS patients [43], single 45 mg doses of L-amphetamine sulfate in MS were associated with improved performance on information processing speed. Morrow et al [44] tested 151 clinically definite MS patients randomized to L-amphetamine or to placebo in a 6-week. The trial results did not confirm any significant improvement on Symbol Digit Modalities Test (SDMT) or on the subjective ratings of cognition.…”