The ISLAND Study: InSuLa Assessed Needs for Depression

Inclusion criteria

• Men or women aged 18-60 years.
• Primary psychiatric diagnosis of Major Depressive Disorder, without psychotic features, confirmed via SCID-IV structured diagnostic interview.
• Screening Hamilton Depression Rating Scale (HAMD) ≥ 18; and Baseline HAMD ≥ 15.
• If the patient is a woman of child-bearing potential, she must agree to use an acceptable form of birth control for duration of study participation.
• Able to understand and provide informed consent for participation.

Exclusion criteria

• Lifetime history of Bipolar Disorder, Dementia, Autism Spectrum Disorder, Schizophrenia, or any other Psychotic Disorder.
• Psychotic symptoms occurring at any time during the current major depressive episode.
• Current (past 12 months) diagnosis of Panic disorder, Obsessive Compulsive Disorder, Posttraumatic Stress Disorder, Anorexia Nervosa, or Bulimia Nervosa.
• Alcohol or Drug Dependence within 12 months or Abuse within 3 months (excluding nicotine and caffeine) of baseline visit, as assessed by history and urine drug screen.
• Clinical evidence of a severe Personality Disorder, as assessed by the study psychiatrist, which would impede participation or completion of the trial.
• Known neurological disorders or documented serious head injury.
• Serious and unstable medical illnesses including cardiovascular disease and cancer.
• Active medical conditions with known mood changes (endocrine, autoimmune disorders).
• Current diabetes mellitus.
• For women, pregnancy, lactation, or unwillingness to comply with birth control requirements.
• Use of any of the following treatments or any other alternative therapy within 2 weeks of the pre-treatment PET scan that may have beneficial effects on mood, including St John's Wort, S-adenosyl methionine (SAMe), n-3 fatty acids, or light therapy.
• Use of antidepressant medication within 1 month of the pre-treatment PET scan (within 5 weeks for fluoxetine and protryptyline).
• Failure to achieve a much improved status (i.e. equivalent to >50% symptom reduction) with 1) any lifetime treatment course of CBT (defined as a minimum of 4 sessions of a specified manual-driven therapy by a CBT-trained therapist) or 2) both escitalopram and sertraline (defined as a minimum of 6 weeks of at the minimum effective dose).
• Clinically significant active suicidal ideation or self-injurious behavior necessitating immediate treatment, as determined by the investigator.
• Received electroconvulsive therapy in the past 6 months or during the current depressive episode.
• Currently responding to medication treatment, without clinical reasons to change.
• Current treatment with weekly individual or group psychotherapy of any type targeted at depressive symptoms.
• QTc >500 milliseconds on EKG at screening.
• Contraindications for MRI, including, but not limited to pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, intra-uterine devices for birth control.
• Use of concomitant medications with the exception of:

• Maintenance or prophylactic therapy for stable medical conditions.
• Hypnotic medication prescribed or approved by the study physician, (up to a three doses per week) for insomnia, as long if not the night before a PET/MRI or clinic ratings visit. Antipsychotic medications, whether prescribed for sleep or other indications, are prohibited.