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