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.

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. The main objective of the study is to evaluate the change in the severity of fatigue in MS patients undergoing treatment with amantadine, TMS and both in combination, compared to placebo. A randomized, placebo-controlled, crossover, double-blind clinical trial will be conducted. As secondary objectives, changes in cognition, depression and quality of life will be evaluated. For all this, the reference scales adequately validated for each of the objectives will be used.

Arms

Experimental: Amantadine

Placebo Comparator: Placebo

Experimental: TMS

Sham Comparator: TMS sham

Interventions

Device: - Transcranial Magnetic Stimulation

TMS is a technique for electrical stimulation of brain tissue by generating a magnetic field, which modulates neural activity at the stimulation site and in interconnected neural networks. The treatment will be applied to the left dorsolateral prefrontal region. Each patient will receive 3 sessions per week of approximately 10 minutes for 6 weeks. In the case of TMS sham, a placebo coil will be used, which is indistinguishable from the therapeutic one. In addition, the sessions will be carried out with the same frequency, so the patient will be unaware of the treatment they are receiving.

Drug: - Amantadine Hydrochloride 100 mg (milligrams) Oral Capsule

It will be used at a dose of 100 mg, 1 capsule a day for 1 week, followed by 2 daily doses of 100 mg until completing 6 weeks in total. After completing the treatment phase, the dose will be de-escalated (1 capsule a day for 5 days and discontinued). In the case of placebo amantadine capsules, they will have the same organoleptic characteristics as amantadine. The start, maintenance and de-escalation pattern will be identical.