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

Not Applicable

Completed

Conditions: Depression

Interventions: Drug: Escitalopram
Drug: Desipramine

Registration Number: NCT00456014

Lead Sponsor: New York State Psychiatric Institute

Brief Summary: This study will use pre-treatment positron emission topography and functional magnetic resonance imaging scans of the brain to predict the most effective antidepressant treatment for people with major depressive disorder.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1 - SSRI	Escitalopram	Participants will receive standardized pharmacotherapy with the SSRI escitalopram over 8 weeks. Non-remitters after 8 weeks will be offered standardized pharmacotherapy with desipramine
1 - SSRI	Desipramine	Participants will receive standardized pharmacotherapy with the SSRI escitalopram over 8 weeks. Non-remitters after 8 weeks will be offered standardized pharmacotherapy with desipramine

Primary Outcome Measures

Name	Time	Method
Remission of Depressive Symptoms	Measured at Week 8	Remission in this study is defined as both a ≥50% decrease in the 24-item Hamilton Depression Rating Scale (HDRS) Score and a final 24-item HDRS score \<10. Remission of depressive symptoms was calculated for the 28 completers of the SSRI phase.

Secondary Outcome Measures

Name	Time	Method
Remission of Depressive Symptoms - Tricyclic Phase	Measured over 8 weeks	Participants who did not achieve remission during the SSRI phase advanced to the tricyclic phase of the study. Participants were treated with either desipramine or nortriptyline. Seven participants started the tricyclic phase. Four completed the tricyclic phase. The completers (n=4) were analyzed for remission status.
Improvement in Scores on the Hamilton Depression Rating Scale - SSRI Phase	Measured at Week 8	Mean % improvement from baseline to end of treatment trial using the 24-item Hamilton Depression Rating Scale. Percent improvement of depressive symptoms was calculated for the 28 completers of the SSRI phase. The higher the score on the 24-item HDRS, the greater the depression severity. Minimum score on the scale is 0, and maximum score is 74. Subscales are not used for this analysis.