Neural Correlates of Psychodynamic Psychotherapy for Depression

In this study, we will treat patients with brief psychodynamic psychotherapy. Psychodynamic
psychotherapy is a type of treatment that may be as helpful as medications in treating
depression. It focuses on thoughts, feelings, and behaviors as well as both current and past
relationships. Psychotherapy explores better ways of coping with feelings, expressing needs,
and interacting with others in order to cope with depression and other life problems.
Subjects will go to 16 weekly, 45-minute, individual sessions of psychodynamic psychotherapy
over the course of the study. At five times throughout the study, subjects will come in for
extra visits, which last approximately 1.5 hours and which include: speaking with a study
doctor about depressive symptoms, filling out extra questionnaires, and performing a
Quantitative Electroencephalogram (QEEG). The QEEG is a machine that measures the electrical
activity of the brain. This task will take approximately 15 minutes.

Subjects will also have the opportunity to participate in an additional positron emission
tomography (PET) component of the study, for which additional compensation will be made
based on the time commitment.

Inclusion Criteria:

- Subjects will be adults, ages 18 to 60 years;

- Able to provide written informed consent;

- MDD, current according to the fourth version of the Diagnostic and Statistical Manual
for Mental Disorders (DSM-IV);

- QIDS-SR score of > 12 at screen;

- Current major depressive episode (MDE) length of < 1 year;

- Treated with an SSRI or SNRI at adequate doses (defined as 20 mg/day or more of
fluoxetine, citalopram, or paroxetine; 10 mg/day or more of escitalopram; 50 mg/day
or more of sertraline; 75 mg/day or more of venlafaxine; 15 mg/day of mirtazapine; or
40 mg/day of duloxetine) during the current episode for at least 8 weeks; and,

- At the time of screen visit, patients must be on a stable dose of SSRI or SNRI for
the past 4 weeks.

Exclusion Criteria:

- Pregnant women or women of child bearing potential who are not using a medically
accepted means of contraception (to include oral contraceptive or implant, condom,
diaphragm, spermicide, intrauterine device, tubal ligation, or a partner with
vasectomy). Women of childbearing age who wish to enter the study will be required to
undergo a pregnancy test (beta-HCG) prior to initiating treatment;

- Patients who, in the investigator's judgment, pose a current, serious suicidal or
homicidal risk. These patients will be immediately referred to appropriate clinical
treatment;

- Patients who, in the opinion of the therapist, are not depressed at the time of their
first psychotherapy visit;

- Patients who are currently being treated by a psychotherapist individually or in a
group or who have received individual or group psychotherapy during the past 6
months. Couples therapy and family therapy will not be considered exclusionary
criteria;

- Patients with neurological illnesses, including a history of seizure or head trauma
with loss of consciousness;

- Patients with unstable diabetes, kidney disease, or significant medical illness;

- Patients with history of allergy to FDG will be excluded from taking part in the PET
portion of the study;

- The following DSM-IV diagnoses: substance use disorders active within the last six
months, any bipolar disorder (current or past), any psychotic disorder (current or
past), any post-traumatic stress disorder (current or past), any obsessive compulsive
disorder (current or past), or any panic disorder (current, past allowed).
Generalized anxiety disorder or adjustment disorder are not exclusionary;

- Patients currently requiring other psychotropic medications, including
anticonvulsants, benzodiazepines, antipsychotics, stimulants, or sedative hypnotics
(other than diphenhydramine);

- Psychotic features in the current episode, or a history of psychotic features, as
assessed by SCID;

- Patients who have undergone > 3 previous adequate attempts at psychodynamic
psychotherapy (deemed "adequate" by the screening physician), which were considered
unhelpful or unsuccessful by patient report (according to patient report);

- Patients with a history of antidepressant-induced hypomania; and

- Patients with a history of medication non-compliance.

- Patients with Axis II pathology (personality disorder) that, in the opinion of the
screening physician, would interfere with subjects' ability to participate in the
treatment and/or comply with the protocol, such as severe borderline or narcissistic
personality disorder.

- Patients who have had electroconvulsive therapy (ECT) within the 12 months preceding
baseline