Improving Therapeutic Learning in Depression: Proof of Concept

Inclusion Criteria: * Must have a DSM diagnosis of major depression as determined by structured diagnostic interview * Must be free of psychotropic medications other than serotonin selective reuptake inhibitors (SSRIs) for at least 2 weeks * No current suicidal ideation * Able to speak and understand English * Must be between the ages of 18 and 65, inclusive * Must be a male, or a female who is not of childbearing potential (i.e., surgically sterile, postmenopausal for at least 1 year) or who is non-pregnant, non-lactating and using a medically accepted method of contraception. Acceptable methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, hormonal contraceptives. A woman of childbearing potential who is not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the trial Exclusion Criteria: * A DSM diagnosis of dementia, neurodegenerative disease, or other organic mental disorder; substance use disorder other than nicotine or caffeine in the last 3 months; bulimia or anorexia within the last 3 months; lifetime history of psychotic disorder or, bipolar disorder, or developmental disorder; * A diagnosis of organic brain syndrome, mental retardation, or other cognitive dysfunction that could interfere with a participants capacity to participate in CBT or to complete safety and efficacy assessments * A history of seizures (apart from childhood febrile seizures) or head trauma causing ongoing cognitive impairment * An uncontrolled, unstable clinically significant medical condition (e.g., renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic or cerebrovascular disease, or malignancy, or poorly controlled hypertension (\> 150/90mmHg) that may interfere with the interpretation of safety and efficacy evaluations in the opinion of the study physician or investigator * Medical illness including hypertension, cardiac disease, liver disease, pulmonary diseases, central nervous system disease, and epilepsy; * Recent (1 year) suicidal attempts or current suicidal ideation * For women, currently pregnant, plans to be pregnant in the next 2 months, or currently breastfeeding * Treatment with phenytoin, isoniazid, or propranolol or known sensitivity to modafinil or cycloserine * A history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment * Use of psychotropic medication (including stimulants) other than SSRIs * Current daily use of alcohol or regular binge alcohol use as determined on the medical screen * Insufficient command of the English language (i.e., cannot carry on a conversation with an interviewer in the English language or read associated text) * Receipt of CBT in the previous five years