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

NCT ID: NCT00456014

Last Updated: 2019-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2012-05-31

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.

Conditions

Depression

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1 - SSRI

Participants will receive standardized pharmacotherapy with the SSRI escitalopram over 8 weeks. Non-remitters after 8 weeks will be offered standardized pharmacotherapy with desipramine

Group Type: EXPERIMENTAL

Escitalopram

Intervention Type: DRUG

Escitalopram will be administered at a dose of 10 mg daily for 4 weeks. If participants have not achieved response (greater than 50 % improvement in Hamilton Depression Rating Scale) by 4 weeks, the dose will be increased to 20 mg. Remission status is determined after an 8-week trial.

Desipramine

Intervention Type: DRUG

Subsequent to escitalopram trial, non-remitters will be offered pharmacotherapy with desipramine. Desipramine will be initiated at a dose of 50 mg and titrated according to a treatment manual, with monitoring of therapeutic blood levels. Remission status is determined after an 8-week trial.

Interventions

Escitalopram

Escitalopram will be administered at a dose of 10 mg daily for 4 weeks. If participants have not achieved response (greater than 50 % improvement in Hamilton Depression Rating Scale) by 4 weeks, the dose will be increased to 20 mg. Remission status is determined after an 8-week trial.

Intervention Type: DRUG

Desipramine

Subsequent to escitalopram trial, non-remitters will be offered pharmacotherapy with desipramine. Desipramine will be initiated at a dose of 50 mg and titrated according to a treatment manual, with monitoring of therapeutic blood levels. Remission status is determined after an 8-week trial.

Intervention Type: DRUG

Other Intervention Names

Lexapro; Norpramin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Miller

assistant professor of clinical psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ramin V. Parsey, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Jeffrey M Miller, MD

Role: PRINCIPAL_INVESTIGATOR

New York State Psychiatric Institute

Locations

Columbia University/New York State Psychiatric Institute

New York, New York, United States

Countries

United States

References

Miller JM, Hesselgrave N, Ogden RT, Zanderigo F, Oquendo MA, Mann JJ, Parsey RV. Brain serotonin 1A receptor binding as a predictor of treatment outcome in major depressive disorder. Biol Psychiatry. 2013 Nov 15;74(10):760-7. doi: 10.1016/j.biopsych.2013.03.021. Epub 2013 May 9.

Reference Type: DERIVED

PMID: 23664414 (View on PubMed)

Other Identifiers

R01MH074813

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DATR A3-NSS

Identifier Type: -

Identifier Source: secondary_id

#6351R (formerly 5206)

Identifier Type: -

Identifier Source: org_study_id