SMART Trial to Predict Anhedonia Response to Antidepressant Treatment
Study Details
Study Description
Brief Summary
The main goal of this research is to use behavioral, brain, and clinical data to determine which type of antidepressant might be optimal before people with depression start treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
The treatment of depression is often trial-and-error. Earlier research reported that only 50% of individuals with depression show a significant decline in symptoms after taking an antidepressant. The situation is even worse in primary care, where only 30% respond to first line antidepressants.
The difficulty in treating depression is likely because treatment selection is not based on each person's characteristics. While some depressed individuals may benefit from selective serotonin reuptake inhibitors (SSRIs), others might benefit more from other types of medication. Finding markers that predict an individual's response to different antidepressants would provide patients and clinicians with valuable information to guide treatment selection.
The present study is among the first to use clinical (e.g., responses on questionnaires), behavioral (e.g., performance in computerized tasks), and brain (e.g., MRI scans) data to guide treatment selection in order to increase the likelihood of benefiting from one of two antidepressants. After analyzing an individuals' markers, subjects will be randomly assigned to receive a full 8-week course of an SSRI or non-SSRI.
Throughout the study, participants will complete 9 total sessions over the course of 9-10 weeks, including an electroencephalogram (EEG) recording, a functional magnetic resonance imaging (fMRI) scan, an electrocardiogram (EKG) exam, interviews with clinicians, and a full 8-week course of an antidepressant.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MDD with SERT+ Response Marker Participants with MDD who have been classified as high sertraline responders based on behavioral and brain data. |
Drug: Sertraline
Subjects will receive 8 weeks of sertraline while monitored by the study physician
Other Names:
Drug: Bupropion
Subjects will receive 8 weeks of bupropion while monitored by the study physician
Other Names:
|
| Experimental: MDD with BUP+ Response Marker Participants with MDD who have been classified as high bupropion responders based on behavioral and brain data. |
Drug: Sertraline
Subjects will receive 8 weeks of sertraline while monitored by the study physician
Other Names:
Drug: Bupropion
Subjects will receive 8 weeks of bupropion while monitored by the study physician
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Score on Montgomery-Asberg Depression Rating Scale (MADRS) [8-10 weeks]
Symptoms of depression
Secondary Outcome Measures
- Ventral-striatal activation during reward related tasks in an fMRI scan [8-10 weeks]
Brain measure of anhedonia
- Effort-based decision making during an effort-based task [8-10 weeks]
Behavioral measure of anhedonia
- Reward positivity during a guessing monetary reward task [8-10 weeks]
Behavioral measure of anhedonia
- Cortico-insular activation during an effort-based task [8-10 weeks]
Brain measure of anhedonia
- Resting state functional connectivity between the NAc and mPFC during an fMRI scan [8-10 weeks]
Brain measure of anhedonia
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Ages 18 to 64
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Any gender and all ethnic/racial origins
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Right-handed
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Diagnosis of Major Depressive Disorder. MDD diagnosis will be decided by clinicians via the Structured Clinical Interview for DSM-5 (SCID-5).
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Elevated depression severity
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Elevated anhedonia symptoms
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Fluency in written and spoken English
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Ability to give signed, informed consent either written or electronic
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Normal or corrected-to-normal vision and hearing
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Ability to adhere to the study schedule
Exclusion Criteria:
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Patient is currently enrolled in any treatment program (psychotherapy, transcranial magnetic stimulation, other antidepressants etc.).
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Any contraindication to bupropion or sertraline considered unsafe by the study physician, or any history of adverse reaction to either drug.
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Failure to respond to an adequate course of treatment with either of the study medications (sertraline or bupropion) during the current episode.
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Participants who are determined to be treatment resistant, (i.e., having failed to respond to at least two adequate antidepressant trials in the current episode)
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Pregnant women, or women of childbearing potential who have a positive result on a urine pregnancy test
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Failure to meet MRI safety requirements, including any metal implants or prostheses that cannot be removed, or exposure to shrapnel
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Claustrophobia or severe anxiety that might affect participation in neuroimaging
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Injury or movement disorder that may make it difficult to lie still in the scanner
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Hairstyles that prevent application of an EEG net (e.g., braids, dreadlocks, cornrows, recently dyed hair)
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Any current recreational/illicit drug use, with the exception of THC, as assessed by a urine drug test (covering cocaine, cannabinoids, opiates, amphetamines, methamphetamines, phencyclidine, MDMA, benzodiazepines, methadone, oxycodone, tricyclic antidepressants, and barbiturates). Participants who use THC regularly will be allowed to continue in the study provided they have abstained for the three days prior to visits involving the MRI scan.
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Use of Monoamine Oxidase Inhibitors (MAOIs) either currently or within the past two weeks
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Participants who are currently stopping the use of tobacco products. Current use of tobacco products is fine as long as subjects do not exceed 10 cigarettes/week.
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More than 15 alcohol-induced lifetime blackouts.
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History of regular use (5-7xs per week) of marijuana before the age of 15
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Lifetime history of other recreational drug use beyond the following limits: 10 uses: Mushrooms; 5 uses: Anxiolytics, cocaine, other hallucinogens (LSD, Ecstasy), opioids, or stimulants (this does not include prescribed stimulants such as methylphenidate). Prescribed opioids for a limited period (e.g., post-surgery) is OK if not in the past 3 months; 1 use: Inhalants, IV drugs, crack cocaine, or crystal methamphetamine
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Recent use (within 3 weeks) of any medication that affects blood flow or blood pressure, or which is vasodilating/vasoconstricting (for participants undergoing neuroimaging)
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Use of Melatonin within 5 days of the MRI scanning procedure
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Metformin use in the past 6 months (for either clinical care or as part of research)
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Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine (hypothyroidism), neurologic, autoimmune disease (such as Lyme, Crohn's), or hematologic disease.
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Current infectious illness (either transient or chronic); Current episode of allergic reaction or asthma
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Hemophilia; Diabetes with poor glucose control; History of chronic migraine (> 15 days/mo.); History of dementia.
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History of seizure disorder.
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Any history of significant head injury or concussion with loss of consciousness for two minutes or more, or head injury with lingering functional/psychological impact
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Serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems (contraindication to bupropion)- confirmed with ECG at physicians' discretion.
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Past/current DSM-5 diagnosis of: OCD, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders NOS, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, autism or any other pervasive developmental disorder, organic mental disorder, PTSD, anorexia, binge eating disorder or bulimia (however a history of PTSD, bulimia, or binge eating disorder is allowable if it has been in remission for at least two years)
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History of moderate or severe substance or alcohol use disorder; or mild substance or alcohol use disorder within the last 12 months (with the exception of cocaine or stimulant abuse, which will lead to automatic exclusion).
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Specific phobia, panic disorder, social anxiety disorder and generalized anxiety disorders will be allowed only if MDD is the principal diagnosis.
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History of Electroconvulsive Therapy.
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Patient is clinically unstable, in the judgment of the clinician or physician.
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Participants with suicidal ideation where continued study participation is believed unsafe by the study clinician or study physician (these participants will be immediately referred to appropriate clinical treatment).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | McLean Hospital | Belmont | Massachusetts | United States | 02478 |
Sponsors and Collaborators
- Mclean Hospital
Investigators
- Principal Investigator: Diego A. Pizzagalli, PhD, Mclean Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022P000896