Is Adderall (amphetamine and dextroamphetamine) effective for treating multiple sclerosis (MS) symptoms?

Adderall for Multiple Sclerosis

Adderall (amphetamine/dextroamphetamine) is not a standard treatment for multiple sclerosis itself, but may be considered off-label specifically for MS-related cognitive impairment or fatigue when these symptoms significantly impact quality of life, though evidence remains limited and other interventions should be tried first. 1, 2

Evidence for Amphetamine Stimulants in MS

Cognitive Impairment

• Lisdexamfetamine (a D-amphetamine prodrug) showed significant improvement in processing speed (SDMT) and verbal memory (CVLT2) in cognitively impaired MS patients in a phase II randomized controlled trial. 2
• L-amphetamine may improve memory specifically in MS patients with existing memory deficits, though data are limited. 1
• The cognitive effects appear most pronounced for processing speed and episodic memory rather than executive function. 2

Fatigue

• Methylphenidate (a related stimulant) is commonly used in clinical practice for MS-related fatigue, though evidence supporting effectiveness remains sparse and conflicting. 3
• A large ongoing trial (TRIUMPHANT-MS) is comparing methylphenidate, modafinil, and amantadine versus placebo for MS fatigue, with results expected but not yet published. 3

Clinical Context and Limitations

MS treatment guidelines do not include Adderall or other amphetamine stimulants as disease-modifying therapies or standard symptomatic treatments. 4, 5

• Disease-modifying therapies (DMTs) remain the cornerstone of MS treatment, targeting the underlying inflammatory process. 5
• For progressive MS specifically, symptomatic management is crucial since disease-modifying drugs have largely failed, but amphetamine stimulants are not among established treatments. 6
• Cognitive rehabilitation and other non-pharmacological approaches should be considered alongside or before pharmacological cognitive enhancement strategies. 1

Safety Considerations in MS Population

The MS population may have unique vulnerabilities when using stimulants:

• MS patients in the lisdexamfetamine trial experienced high rates of adverse events (73.5%), though no serious adverse events occurred. 2
• Cardiovascular monitoring (blood pressure and pulse) is essential with stimulant use. 7
• Patients with MS may have comorbid conditions (depression, anxiety, fatigue) that complicate stimulant use. 6

Contraindications Apply

Standard stimulant contraindications remain relevant: 4, 7

• Concomitant MAO inhibitor use (absolute contraindication)
• Active psychotic disorder
• Symptomatic cardiovascular disease or uncontrolled hypertension
• History of stimulant abuse (relative contraindication requiring careful monitoring)

Practical Approach

If considering amphetamine stimulants for MS-related cognitive impairment or fatigue:

1. Ensure the patient is on appropriate disease-modifying therapy first, as some DMTs may improve cognitive performance. 1
2. Document specific cognitive deficits (processing speed, memory) or fatigue severity that significantly impairs quality of life. 2, 6
3. Trial other evidence-based interventions first, including cognitive rehabilitation for cognitive symptoms. 1
4. Start with lower doses (e.g., 30 mg lisdexamfetamine or equivalent) and titrate based on response and tolerability. 2
5. Monitor cardiovascular parameters and watch for behavioral adverse effects. 7, 2
6. Reassess benefit after 8 weeks of optimal dosing, as this was the trial duration showing benefit. 2