The investigators propose to conduct a randomized Sequential Parallel Design for Double-Blind Phase fixed dose, 4-month trial of folate plus B12 as add-on therapy in 200 Ethiopian subjects with schizophrenia with stable residual positive or negative symptoms.

This is a 16-week, randomized, double-blind, placebo-controlled study of Folate 2mg plus B12 400mcg, as an adjunctive therapy in approximately 240 consecutive outpatients with schizophrenia from Amanuel Hospital, which is based at Addis Ababa, Ethiopia will be enrolled and screened for eligibility. The goal is to randomize and complete 200 subjects from the 240 enrolled. A Sequential Parallel Design for Double-Blind Phase will be utilized. During the first phase of double-blind adjunctive treatment, eligible patients (n=200) are randomized to adjunctive treatment with either folate and vitamin B12 (n=60) or placebo (n=150), with a 2:3:3 ratio for random assignment to the treatment sequences drug/drug (DD; n=70), placebo/placebo (PP; n=70), and placebo/drug (PD; n=75), while all continue to receive their antipsychotic agent for the entire duration of the study. Assuming a 10% drop-out rate during the first phase, 126 patients on placebo will complete the first 56-day phase, and 54 patients on folate and vitamin B12 will complete the first 56-day phase.

Inclusion Criteria:

1. Diagnosis of schizophrenia, any subtype
2. Male or female
3. Age 18-65 years
4. Treated with an antipsychotic for at least 6 months at a stable dose for at least 6 weeks
5. PANSS total score of at least 60, with at least a 3 (moderate) on one negative symptom item or on one positive symptom item.
6. No acute medical problems; any chronic medical condition (e.g. hypertension) consistently treated and stable during the 1 month prior to participation

Exclusion Criteria:

1. Unable to provide informed consent
2. Serum B12 concentration less than 300mcg/L; Complete Blood Count (CBC) results consistent with megaloblastic anemia
3. Serum creatinine concentration greater than 1.4
4. Current use of folate or B12 supplementation
5. Current use of any of the following medications: phenobarbital, phenytoin, carbamazepine, valproic acid, fosphenytoin, primidone or pyrimethamine; antimalarial drugs
6. Alcohol or other substance abuse within 3 months (nicotine allowed)
7. Subjects with a history of clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorders (e.g. unstable angina, decompensated congestive heart failure, Central Nervous System (CNS) infection or history of HIV seropositivity), which would pose a risk to the patient if they were to participate in the study or that might confound the results of the study. Active medical conditions that are minor or well controlled are not exclusionary if they do not affect risk to the patient or the study results. For example, the following are not exclusionary: a) stable and well- controlled hypertension; b) asthma (no serious attacks in the past year)
8. Unstable psychiatric illness
9. Seizure disorder
10. Pregnancy or nursing