Pre-Treatment Positron Emission Topography Scanning for Increasing Success in Antidepressant Treatment

Major depressive disorder (MDD) is characterized by a combination of symptoms that can
interfere with a person's ability to work, study, sleep, eat, and enjoy activities that were
once pleasurable. Studies have shown that as little as 50% to 60% of individuals with MDD may
respond to the first antidepressant medication prescribed. Currently psychiatrists lack tools
that allow them to select the treatment plan that is most likely to benefit a particular
individual. Some of the chemical abnormalities in the brains of people with MDD are
detectable on positron emission topography (PET) scans. There are distinct differences in the
PET scans of people with MDD who respond to treatment with a selective serotonin reuptake
inhibitor (SSRI), people with MDD who do not respond to SSRI treatment, and people who do not
have MDD. This study will use pretreatment PET and functional magnetic resonance imaging
(fMRI) scans of the brain to predict which antidepressants will be most effective in people
with MDD. This may help to reduce the trial and error currently associated with
antidepressant treatment.

We will perform pretreatment PET scans to quantify serotonin transporter (5-HTT) and
serotonin 1A (5-HT1A) receptor in patients with major depressive disorder (MDD). All patients
will then receive a standardized treatment protocol with a selective serotonin reuptake
inhibitor (SSRI), escitalopram. If the patient does not remit, he or she will receive a
selective norepinephrine reuptake inhibitor (NRI), desipramine. We hypothesize those patients
with high pre and postsynaptic 5-HT1A BP and low 5-HTT BP in specific brain regions will not
remit to a SSRI and will remit to a selective NRI. Finally, we will generate a predictive
model of remission based on brain imaging outcome measures. Our overall goal is to reduce the
trial and error associated with antidepressant treatment by using data from pre-treatment
quantification of 5-HT1A receptors and 5-HTT to guide antidepressant treatment selection.

Inclusion Criteria:

- Diagnosis of current major depressive disorder

- Currently depressed

- Subjects must be generally healthy with no significant medical problems, anemia/blood
loss, or cardiac abnormalities

- Likely to tolerate medication washout

- Capacity to provide informed consent

- Off of anti-coagulant/anti-platelet treatment for 10 days

- Willing to travel to Brookhaven for PET scanning

Exclusion Criteria:

- Current abuse of or dependence on alcohol or another substance (>6 months remission
okay)

- History of other major psychiatric disorders such as bipolar, schizophrenia,
schizoaffective; anorexia or bulimia in past year

- First degree family history of schizophrenia if subject is under 33

- Unable/unwilling to discontinue all psychotropic medication that affects the serotonin
system

- Pregnant, breastfeeding, or planning to become pregnant during the study

- A medical contraindication to antidepressants

- Dementia

- Prior head trauma with evidence of cognitive impairment

- Well-documented failure of two or more SSRI AND tricyclic antidepressant (TCA) trials
of adequate dose and duration

- Metal implants, pacemaker, metal protheses or orthodontic appliance, the presence of
shrapnel

- Current past, present, or anticipated exposure to radiation

- Actively suicidal

- Lifetime history of glaucoma

- Lack of response to >2 trials of antidepressant monotherapy of adequate dose and
duration

- Claustrophobia