The purpose of this study is to determine whether lithium carbonate is safe, well-tolerated, and effective at treating progressive forms of multiple sclerosis.

In progressive multiple sclerosis (MS), patients experience worsening disability through a combination of inflammatory and neuro-degenerative processes. To test whether low-dose lithium carbonate ameliorates disability accumulation in progressive MS, patients with progressive MS were randomly assigned to take lithium in either the first or second year of a two-year trial. The trial was designed as a cross-over study to maximize exposure to lithium to for two reasons: 1) To increase the number of persons with MS exposed to lithium for purposes of assessing safety and tolerance; and 2) To increase the power to detect changes in the primary radiological outcome (change in brain volume) and also in secondary clinical outcomes (disability, mood, fatigue, cognition).

Inclusion Criteria:

• Diagnosis of a progressive subtype of multiple sclerosis by revised 2005 McDonald Criteria.
• EDSS of 3.0-6.5
• Ages 30-65
• Must be mentally capable of providing informed consent and following study guidelines.

Exclusion Criteria:

• Relapse or steroid treatment within 1 month of trial entry.
• Any current or previous treatment with mitoxantrone, azathioprine, methotrexate, mycophenolate, cyclophosphamide, or any experimental therapy.
• Women who are pregnant, wishing to become pregnant in the coming 30 months, or are breastfeeding.
• Sexually active women unwilling to use reliable contraception (oral contraceptives, condom, IUD).
• Patients with known kidney dysfunction or creatinine >1.4; known cardiac arrhythmia or significant conduction abnormality on EKG; uncontrolled thyroid disease or TSH >20% above the upper limit of normal; uncontrolled psoriasis, HIV, or any other severe medical condition.
• Patients with a history of unstable psychiatric illness or active severe depression.
• Patients with a history of seizure.
• Concurrent use of any of the following medications: Antipsychotics, diuretics, digoxin, or iodide salts.
• Use of non-steroidal anti-inflammatory drugs (NSAIDs) 5 or more days a week.
• Patients with a history of substance abuse in the past year.
• Patients sensitive to gadolinium, or who are unable to undergo the required number of MRI scans.
• Unable to speak or understand sufficient English to consent or complete study procedures.
• Patients unable or unwilling to provide informed consent.

Adverse events were collected over the entire period of study involvement (2 years). For each subject, 1 year was observation and the other year subjects were taking the study medication, lithium carbonate.

Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.

This was a pilot study and thus by design was not powered to detect therapeutic differences. The primary purpose of the study was feasibility with the specified outcomes intended to generate preliminary data for subsequent research.