Precision Care for Major Depressive Disorder

This study aims to assess whether phenotyping-guided intervention selection is superior to intervention selection without phenotyping guidance (i.e., routine clinician and patient judgment regarding treatment selection) for depression.

Study Overview

• Status: Enrolling by invitation
• Conditions: Depression; Depressive Disorder, Major; Major Depressive Disorder
• Intervention / Treatment: Drug: Pramipexole; Other: Care as usual (CAU) plan; Drug: Methylphenidate; Behavioral: Mindfulness-based Stress Sensitivity Therapy (MBSST); Drug: Phenelzine; Behavioral: Complicated Grief Treatment (CGT)

Detailed Description

This study will classify patients seen in the Depression Clinic of the UCSF Department of Psychiatry and Behavioral Sciences into one of five phenotypes (subtypes), including: 1) Anhedonia, 2) Cognitive deficits, 3) Stress sensitivity, 4) Anxious distress, and 5) Grief.

After phenotyping, participants will be randomized to receive phenotype-specific intervention (PSI) or care as usual (CAU).

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94107
      • Nancy Friend Pritzker Psychiatry Building, University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant is able to provide informed consent
• English speaker
• 18 years of age or older at time of consent
• Meets DSM-5 criteria for Major Depressive Disorder
• The subject meets eligibility criteria for at least one study phenotype as determined by assessments, imaging and/or clinical judgment.
• PHQ-8 score at baseline of >= 10
• Scheduled for or completed intake in UCSF outpatient psychiatry

Exclusion Criteria:

• Unstable or untreated medical or psychiatric condition based on clinical assessment by investigator(s)
• Significant risk of suicidal or violent behavior as determined by clinical judgement
• In the Investigators' opinion, the subject is not capable of adhering to the protocol requirements, or the subject has a history of poor or suspected poor compliance in clinical research studies, or the subject has a history of poor or suspected poor compliance to antidepressant medication or that study participation is not in their best interest (e.g., different treatment is indicated given their clinical presentation)
• Pregnant or breastfeeding or planning to become pregnant during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anhedonia phenotype: PSI	Drug: Pramipexole; CAU plan modified to include a trial of pramipexole.
Active Comparator: Anhedonia phenotype: CAU	Other: Care as usual (CAU) plan; Unmodified CAU plan.
Experimental: Cognitive deficits: PSI	Drug: Methylphenidate; CAU plan modified to include a trial of methylphenidate (or, if contraindicated: guanfacine).
Active Comparator: Cognitive deficits: CAU	Other: Care as usual (CAU) plan; Unmodified CAU plan.
Experimental: Stress sensitivity: PSI	Behavioral: Mindfulness-based Stress Sensitivity Therapy (MBSST); CAU plan modified to include a trial of MBSST. MBSST is an individual psychotherapy delivered approximately weekly for 16 sessions.
Active Comparator: Stress sensitivity: CAU	Other: Care as usual (CAU) plan; Unmodified CAU plan.
Experimental: Anxious distress: PSI	Drug: Phenelzine; CAU plan modified to include a trial of phenelzine (or, if contraindicated: brexpiprazole).
Active Comparator: Anxious distress: CAU	Other: Care as usual (CAU) plan; Unmodified CAU plan.
Experimental: Grief: PSI	Behavioral: Complicated Grief Treatment (CGT); CAU plan modified to include a trial of CGT.
Active Comparator: Grief: CAU	Other: Care as usual (CAU) plan; Unmodified CAU plan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quick Inventory of Depressive Symptoms - Self-Report 16-Item (QIDS-SR-16) score	Within-phenotype and across-phenotype contrasts.	Up to 24 weeks after randomization.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Snaith-Hamilton Pleasure Scale (SHAPS) score	For anhedonia phenotype only.	Up to 24 weeks after randomization.
Clinically Useful Depression Outcome Scale Anxious Distress Specifier Subscale (CUDOS-A) score	For anxious distress phenotype only.	Up to 24 weeks after randomization.
Generalized Anxiety Disorder 7-item (GAD-7) score	For anxious distress phenotype only.	Up to 24 weeks after randomization.
Inventory of Complicated Grief (ICG) score	For grief phenotype only.	Up to 24 weeks after randomization.
Perceived Deficits Questionnaire - Depression (PDQ-D) score	For cognitive deficits phenotype only.	Up to 24 weeks after randomization.
Patient Health Questionnaire - 8 (PHQ-8) score	Within-phenotype and across-phenotype contrasts.	Up to 24 weeks after randomization.
WHO Disability Assessment Schedule (WHODAS 2.0)	Within-phenotype and across-phenotype contrasts.	Up to 24 weeks after randomization.
Quick Inventory of Depressive Symptoms - Self-Report 16-Item (QIDS-SR-16) response	50% reduction from baseline score. Within-phenotype and across-phenotype contrasts.	Up to 24 weeks after randomization.
Quick Inventory of Depressive Symptoms - Self-Report 16-Item (QIDS-SR-16) remission	Score < 6. Within-phenotype and across-phenotype contrasts.	Up to 24 weeks after randomization.

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Andrew D. Krystal, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: August 28, 2024
• First Submitted That Met QC Criteria: August 28, 2024
• First Posted (Actual): August 30, 2024

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depressive Disorder; Behavior; Depression; Depressive Disorder, Major; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Benzothiazoles; Azoles; Carboxylic Acids; Piperidines; Acids, Carbocyclic; Phenylacetates; Hydrazines; Pramipexole; Methylphenidate; Phenelzine
• Other Study ID Numbers: 24-41815

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No