Rapid Antidepressant Improvement Secondary to Excitatory Brain Responses

Prior treatment

• Receiving vagus nerve stimulation, electroconvulsive therapy, or repetitive Transcranial Magnetic Stimulation during the current episode.
• Currently taking any psychiatric medication or other potential augmenting agents (e.g., T3 in the absence of thyroid disease, lithium, buspirone); Taking thyroid medication for hypothyroidism may be included only if they have been stable on the thyroid medication for 3 months;
• Receiving therapy that is depression specific, such as Cognitive Behavioral Therapy or Interpersonal Psychotherapy of Depression (participants can participate if they are receiving psychotherapy that is not targeting the symptoms of depression, such as supportive therapy, marital therapy);
• Patients are receiving opioid analgesics.
• Having any contraindication for the performance of an MRI, such as the presence of metal implants or foreign metallic objects (e.g., braces or extensive dental work), severe claustrophobia, or inability to tolerate the scanning procedures.

Other illness

• History (lifetime) of psychotic depressive, schizophrenic, bipolar (I, II, or NOS), schizoaffective, or other Axis I psychotic disorders;
• Requiring immediate hospitalization for psychiatric disorder or have an unstable general medical condition (GMC) that will likely require hospitalization or to be deemed terminal (life expectancy \< 6 months after study entry);
• Having epilepsy or other conditions requiring an anticonvulsant;
• Any individual with a history of sensitivity to buprenorphine or naltrexone.
• Having any contraindication for the performance of TMS, such as the presence of a neurologic disorder or medication therapy known to alter seizure threshold (e.g., stroke, aneurysm, brain surgery, structural brain lesion, brain injury, frequent/severe headaches), recurrent seizures or epilepsy in participant or family history of hereditary epilepsy, pregnancy, metallic implants in body or other devices that may be affected by magnetic field or significant heart disease or cerebrovascular disease.

Other

• Pregnant or breastfeeding or plan to become pregnant over the duration of the study;
• Meeting M.I.N.I. criteria for substance dependence in the last 6 months, except for nicotine, or substance abuse in the last 2 months;
• Currently actively suicidal or considered a high suicide risk;
• Patients are currently dependent on opioids.
• Patients are in acute opioid withdrawal.
• Any individual who has failed the naloxone challenge test or who has a positive urine screen for opioids.
• Currently enrolled in another study, and participation in that study contraindicates participation in this study;
• Any reason not listed herein yet, determined by the site PI and research staff that makes participation in the study hazardous.

• Adults, age 18-55 years; fluent in English;
• Written informed consent obtained;
• Depressive symptoms with or without certain anxiety disorders (e.g., generalized anxiety, panic, agoraphobia, social phobia, and specific phobia);
• No more than one failed antidepressant trial of adequate dose and duration, as defined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ);
• Participants can have previous history of antidepressant treatment but will need to be antidepressant medication-free for at least 21 days prior to the collection of imaging data (five weeks for fluoxetine).