Overview

Multiple Sclerosis (MS) is the most frequent cause of non-traumatic disability in people under 55 years of age. Fatigue is the most frequent and disabling symptom in the disease, and for which there is no effective treatment. Among the proposed drugs, amantadine is the one that could be most useful, although up to now it has not been adequately demonstrated due to a lack of sufficiently powerful and methodologically appropriate clinical trials. Transcranial magnetic stimulation (TMS) has recently been proposed as a useful treatment for fatigue in MS in preliminary studies.

Eligibility

Inclusion Criteria:

1. Expanded Disability Status Scale mark 1.5 - 4.5
2. Fatigue Severity Scale > 4
3. Beck Depression Inventory < 30
4. No relapse for, at least, three month prior to screening
5. Drug washout period = 4 weeks for any fatigue aimed drug
6. Patient capable to sign the informed consent

Exclusion Criteria:

1. Fatigue causing disease other than multiple sclerosis:
   1. sleep apnea
   2. other autoimmune disease that could be explain the fatigue.
   3. endocrine autoimmune disease if the blood test is not in range in the last 6 month.
   4. patient with diagnosis of chronic fatigue
   5. Patient with high blood pressure out of range or decompensated heart failure or New York Heart Association (NYHA) 3-4.
2. Secondary Epilepsy or neuropathic chronic pain which requires continuous treatment.
3. Contraindication for trial treatment:
   1. Some kind of magnetic metal.
   2. Epilepsy antecedents.
   3. Any drugs that could decrease the seizure threshold
   4. Amantadine sensitivity
   5. Cardiopathy disease, severe kidney failure, Angle-closure glaucoma
4. Breastfeeding, pregnancy, or pregnancy planning phase in the next year. Of

   childbearing potential and willing to use an acceptable method of contraception during the study period.

5. Patient with a terminal disease with no more than one year life expectancy.
6. Patient has been treated for a maligned disease in the past three years.
7. A scheduled surgery in the course of the trials.
8. Any condition that a member of research team consider could affect to participation/follow up patient.
9. Alcoholic o toxics condition in the last year.
10. Major mental disorders
11. Poor communication skills or poor cognitive condition.
12. Other trial participation in the previous 4 month.
13. Use a chronic drug that could interfere in the clinical outcome.