Cysteamine Therapy for Major Depressive Disorder

Inclusion Criteria: 1. Male or female patients, 21-65 years of age. 2. Female subjects who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or must be using a medically accepted means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum B-HCG at pre-study. 3. Subjects must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, (SCID-P). 4. Subjects have a history of at least one previous episode of depression prior to the current episode (recurrent major depressive disorder) or have chronic major depressive disorder (at least two years' duration). 5. Subjects have not responded to an adequate trial of one antidepressant in the current episode as determined by Antidepressant Treatment History Form (ATHF) criteria (score \> 3) (Sackeim 2001) 6. Subjects must have an initial score of ³ 32 on the IDS-C at both Visit 1 and Visit 2. 7. Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document. 8. Current major depressive episode is of at least 4 weeks duration Exclusion Criteria: 1. Presence of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or bipolar disorder/cyclothymia as defined in the DSM-IV. 2. Lifetime histories of autism, mental retardation, pervasive developmental disorders, OCD, or Tourette's 3. Current Eating Disorder 4. Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for nicotine or caffeine) within the preceding 3 months. 5. Female subjects who are either pregnant or nursing. 6. Serious, unstable illnesses including hepatic, renal, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease. 7. Hypersensitivity to cysteamine or penicillamine 8. Past history of severe gastrointestinal disease (including peptic ulcers or inflammatory bowel disease), or current gastroesophageal reflux disease 9. Subjects with a history of neutropenia or medication-induced blood dyscrasia. 10. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG. 11. Subjects with uncorrected hypothyroidism or hyperthyroidism. 12. Subjects with one or more seizures without a clear and resolved etiology. 13. Treatment with a reversible MAOI within 2 weeks prior to Visit 2. 14. Treatment with fluoxetine within 4 weeks prior to Visit 2. 15. Treatment with any other concomitant medication not allowed 14 days prior to study Visit 2. 16. Treatment with clozapine or ECT within 3 months prior to study Visit 2. 17. Judged clinically to be at serious suicidal or homicidal risk. 18. Participation in a clinical trial of another investigational drug within 1 month prior to study entry. 19. Patients starting hormonal treatment (e.g., estrogen) in the last 3 months prior to visit 1. 20. Psychotherapy or nonpharmacological antidepressant treatments (e.g. light therapy