Predictors of Antidepressant Response - Full Text View

Purpose

Major depression is a highly prevalent, frequently debilitating illness that too often fails to respond to currently available treatments such as antidepressant medication. Furthermore, randomized controlled trials of antidepressants consistently demonstrate large placebo effects. The investigators hypothesize that individual differences in the function of key brain circuits underlie the observed variability in clinical responses to both placebo and antidepressant medication. This study will test this hypothesis by recruiting treatment-seeking volunteers with major depression, with or without comorbid nicotine dependence. Volunteers will participate in positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scans in the context of a treatment trial in which they will receive both placebo and antidepressant medication. A major goal of the study is to improve prediction of individual clinical responses in future treatment trials in which brain imaging may be unavailable, and to study the mechanisms of antidepressant response in Major Depression.

Condition	Intervention	Phase
Depression	Other: Placebo, identified as placebo to participants Drug: Celexa or other antidepressant as clinically indicated Other: Placebo, identifed to participants as "Active medication"	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Participant Primary Purpose: Other
Official Title:	Predictors of Antidepressant Response

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants

Drug Information available for: Citalopram hydrobromide Citalopram Escitalopram oxalate

U.S. FDA Resources

Further study details as provided by Jon-Kar Zubieta, University of Michigan:

Primary Outcome Measures:

Changes in mu-opioid and dopamine binding potential during PET [ Time Frame: (90 minute PET scans) assessed at Weeks 1 and 2 ]
Changes in BOLD response during reward and decision making fMRI tasks [ Time Frame: (90 minute fMRI scans) assessed at Weeks 1 and 2 ]

Secondary Outcome Measures:

Depression severity will be assessed with several questionnaires [ Time Frame: At initial screening, Week 0, Week 2, Week 4, Week 8, and Week 10 visits, or until the participants leave the study. ]
We will be using the Patient Health Questionnaire-9, Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16).

Other Outcome Measures:

Blood samples [ Time Frame: Week 1 and Week 2 ]
5mL collected for analysis of genetic information, hormone levels, and cortisol levels
Neuropsychological test results [ Time Frame: at baseline and Week 10 ]
Affect processing: Emotional Words Task and Facial Emotion Perception test. Attention and Inhibitory Control: Parametric Go/NoGo, Trail Making test and the Stroop Color Word test . Inferential Reasoning (including cost-benefit analysis): Delayed Discounting of Money Rewards, Iowa Gambling Task, and the Wisconsin Card Sorting Test. Visual Perception: Benton Visual Discrimination Form.


Enrollment:	44
Study Start Date:	January 2011
Study Completion Date:	October 2015
Primary Completion Date:	October 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Known Placebo First This arm gets a placebo that they know is a placebo (called inactive), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "active medication" (which is also actually a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa or alternative as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.	Other: Placebo, identified as placebo to participants White tablets Drug: Celexa or other antidepressant as clinically indicated Open label s-citalopram, 20 mg start up dose, increasing to 40 mg as clinically indicated; If prior non-response to this medication is noted by the patient, alternative treatments may include another first-line antidepressant:fluoxetine 20 mg; paroxetine up to 60 mg; sertraline up to 200 mg; bupropion up to 300 mg Other Name: S-citalopram 20-40 mg orally Other: Placebo, identifed to participants as "Active medication" Blue Capsule
Experimental: "Active" (blinded) Placebo first group This arm gets a placebo that they don't know is a placebo (called Active), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "inactive medication" (which participants know is a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.	Other: Placebo, identified as placebo to participants White tablets Drug: Celexa or other antidepressant as clinically indicated Open label s-citalopram, 20 mg start up dose, increasing to 40 mg as clinically indicated; If prior non-response to this medication is noted by the patient, alternative treatments may include another first-line antidepressant:fluoxetine 20 mg; paroxetine up to 60 mg; sertraline up to 200 mg; bupropion up to 300 mg Other Name: S-citalopram 20-40 mg orally Other: Placebo, identifed to participants as "Active medication" Blue Capsule

Arms

Assigned Interventions

Experimental: Known Placebo First

This arm gets a placebo that they know is a placebo (called inactive), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "active medication" (which is also actually a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa or alternative as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.

Other: Placebo, identified as placebo to participants

White tablets

Drug: Celexa or other antidepressant as clinically indicated

Open label s-citalopram, 20 mg start up dose, increasing to 40 mg as clinically indicated; If prior non-response to this medication is noted by the patient, alternative treatments may include another first-line antidepressant:fluoxetine 20 mg; paroxetine up to 60 mg; sertraline up to 200 mg; bupropion up to 300 mg

Other Name: S-citalopram 20-40 mg orally

Other: Placebo, identifed to participants as "Active medication"

Blue Capsule

Experimental: "Active" (blinded) Placebo first group

This arm gets a placebo that they don't know is a placebo (called Active), then has 2 scans performed (FMRI and PET), then a 2-3 day washout, and then gets a so-called "inactive medication" (which participants know is a placebo), and another pair of scans. Following these, participants receive 10 weeks of open-label antidepressant administration (Celexa as explained in intervention description). First line antidepressant will be Celexa unless not clinically indicated.

Other: Placebo, identified as placebo to participants

White tablets

Drug: Celexa or other antidepressant as clinically indicated

Open label s-citalopram, 20 mg start up dose, increasing to 40 mg as clinically indicated; If prior non-response to this medication is noted by the patient, alternative treatments may include another first-line antidepressant:fluoxetine 20 mg; paroxetine up to 60 mg; sertraline up to 200 mg; bupropion up to 300 mg

Other Name: S-citalopram 20-40 mg orally

Other: Placebo, identifed to participants as "Active medication"

Blue Capsule

Eligibility


Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria: Inclusion criteria will include:

Participants diagnosed with Major Depressive Disorder and will include Hamilton Depressive Rating Scale (HDRS) scores >15

Exclusion Criteria:

Comorbid conditions that are medical, neurological or psychiatric, pregnancy, use of hormones (including birth control) or use of psychotropic agents
We will only permit certain past anxiety disorder diagnoses, including generalized anxiety, panic, agoraphobia, social phobia
We also will exclude left-handed individuals and patients who have used any centrally acting medications or recreational drugs with the past 2 months
No history of an implant, pacemaker or pacemaker wires, open heart surgery, artificial heart valve, brain aneurysm surgery, middle ear implant, hearing aid, braces or extensive dental work, cataract surgery or lens implant, implanted mechanical or electrical device, or artificial limb or joint
No metallic object in their body (such as braces) or have a history of foreign metallic object in the body such as bullets, BB's, pellets, shrapnel, or other metal fragments

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02178696

Locations


United States, Michigan
Department of Psychiatry
Ann Arbor, Michigan, United States, 48108

Sponsors and Collaborators

University of Michigan

Investigators


Principal Investigator:	Jon-Kar Zubieta, MD, PhD	University of Michigan

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Peciña M, Bohnert AS, Sikora M, Avery ET, Langenecker SA, Mickey BJ, Zubieta JK. Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression. JAMA Psychiatry. 2015 Nov;72(11):1087-94. doi: 10.1001/jamapsychiatry.2015.1335.


Responsible Party:	Jon-Kar Zubieta, MD PhD, University of Michigan
ClinicalTrials.gov Identifier:	NCT02178696 History of Changes
Other Study ID Numbers:	HUM00033328
Study First Received:	June 12, 2014
Last Updated:	March 21, 2017

Additional relevant MeSH terms:


Antidepressive Agents Citalopram Dexetimide Psychotropic Drugs Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Serotonin Agents	Physiological Effects of Drugs Antidepressive Agents, Second-Generation Antiparkinson Agents Anti-Dyskinesia Agents Parasympatholytics Autonomic Agents Peripheral Nervous System Agents Muscarinic Antagonists Cholinergic Antagonists Cholinergic Agents

ClinicalTrials.gov processed this record on August 16, 2017