What evidence supports the use of Adderall (amphetamine and dextroamphetamine) in patients with Multiple Sclerosis (MS)?

Evidence for Adderall Use in Multiple Sclerosis Patients

Direct Evidence from Clinical Trials

Two peer-reviewed studies provide evidence supporting amphetamine use in MS patients, specifically for cognitive impairment:

Study 1: Lisdexamfetamine (Amphetamine Prodrug) for Cognitive Impairment

• A phase II randomized, placebo-controlled, double-blind trial demonstrated that lisdexamfetamine dimesylate (a D-amphetamine prodrug) significantly improved processing speed and memory in cognitively impaired MS patients 1
• The study enrolled 63 MS patients with documented cognitive impairment, randomized 2:1 to receive lisdexamfetamine (30-70 mg) or placebo for 8 weeks 1
• Results showed significant improvement in the Symbol Digit Modalities Test (SDMT) score (+4.6 vs. +1.3 points, p<0.05) and California Verbal Learning Test (CVLT2) score (+4.7 vs. -0.9 points, p<0.05) compared to placebo 1
• The medication was generally well-tolerated with no serious adverse events, though 73.5% of treated subjects reported adverse events versus 68.4% on placebo 1

Study 2: Mixed Amphetamine Salts for Processing Speed

• A randomized, double-blind, placebo-controlled study of mixed amphetamine salts extended-release (MAS-XR, the generic name for Adderall XR) demonstrated significant improvement in processing speed in MS patients with a single 10 mg dose 2
• The study enrolled 52 MS patients with documented processing speed impairment on standardized testing 2
• The 10 mg MAS-XR dose produced a statistically significant improvement in SDMT scores (+5.2 ± 4.5 points) compared to placebo (+0.6 ± 4.4 points, p=0.043), with a medium effect size of 0.47 2
• This single-dose study supports the potential for MAS-XR as a treatment option and warranted larger longitudinal investigation 2

Important Context and Limitations

Lack of Evidence for Fatigue Management

• Despite common clinical use, a large randomized crossover trial (TRIUMPHANT-MS) found that methylphenidate (a related stimulant) was NOT superior to placebo for MS-related fatigue and caused more frequent adverse events 3
• This 141-patient study compared methylphenidate, modafinil, and amantadine to placebo, finding no significant difference in Modified Fatigue Impact Scale scores (p=0.20) 3
• Methylphenidate caused adverse events in 40% of patients compared to 31% with placebo 3

Systematic Review Findings

• A systematic review of pharmacological interventions for MS-related fatigue found no strong evidence supporting stimulant use for this indication 4
• The review identified that no pharmacological intervention had strong evidence for improving MS-related fatigue 4

Clinical Implications

The evidence supports amphetamine use specifically for cognitive impairment (processing speed and memory deficits) in MS patients, but NOT for fatigue management:

• Both studies demonstrating benefit focused on objective cognitive outcomes using validated neuropsychological tests (SDMT, CVLT2) rather than subjective fatigue measures 1, 2
• The cognitive benefits were measurable and clinically meaningful, with medium effect sizes 2
• Amphetamines should be considered for MS patients with documented cognitive impairment on standardized testing, particularly those with slowed processing speed 1, 2

Safety Considerations

• Both studies reported acceptable safety profiles with no serious adverse events in the amphetamine-treated groups 1, 2
• However, clinicians should monitor for typical stimulant adverse effects including cardiovascular changes, insomnia, and potential for abuse 5
• Contraindications include psychosis, uncontrolled hypertension, and concurrent MAO inhibitor use 5