Precision Care for Major Depressive Disorder

NCT06580041 | Enrolling By Invitation Phase 4 FDA Drug

• 1 other identifier: 24-41815
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depressive Disorder; Depression; Depressive Disorder, Major

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Snaith-Hamilton Pleasure Scale (SHAPS) score

  Up to 24 weeks after randomization.

• Clinically Useful Depression Outcome Scale Anxious Distress Specifier Subscale (CUDOS-A) score

  Up to 24 weeks after randomization.

• Generalized Anxiety Disorder 7-item (GAD-7) score

  Up to 24 weeks after randomization.

• Inventory of Complicated Grief (ICG) score

  Up to 24 weeks after randomization.

• Perceived Deficits Questionnaire - Depression (PDQ-D) score

  Up to 24 weeks after randomization.

Study Arms (10)

Anhedonia phenotype: PSI

EXPERIMENTAL

Drug: Pramipexole

Anhedonia phenotype: CAU

ACTIVE COMPARATOR

Other: Care as usual (CAU) plan

Cognitive deficits: PSI

EXPERIMENTAL

Drug: Methylphenidate

Cognitive deficits: CAU

ACTIVE COMPARATOR

Other: Care as usual (CAU) plan

Stress sensitivity: PSI

EXPERIMENTAL

Behavioral: Mindfulness-based Stress Sensitivity Therapy (MBSST)

Stress sensitivity: CAU

ACTIVE COMPARATOR

Other: Care as usual (CAU) plan

Anxious distress: PSI

EXPERIMENTAL

Drug: Phenelzine

Anxious distress: CAU

ACTIVE COMPARATOR

Other: Care as usual (CAU) plan

Grief: PSI

EXPERIMENTAL

Behavioral: Complicated Grief Treatment (CGT)

Grief: CAU

ACTIVE COMPARATOR

Other: Care as usual (CAU) plan

Interventions

Pramipexole DRUG

CAU plan modified to include a trial of pramipexole.

Anhedonia phenotype: PSI

Methylphenidate DRUG

CAU plan modified to include a trial of methylphenidate (or, if contraindicated: guanfacine).

Cognitive deficits: PSI

Phenelzine DRUG

CAU plan modified to include a trial of phenelzine (or, if contraindicated: brexpiprazole).

Anxious distress: PSI

Mindfulness-based Stress Sensitivity Therapy (MBSST) BEHAVIORAL

CAU plan modified to include a trial of MBSST. MBSST is an individual psychotherapy delivered approximately weekly for 16 sessions.

Stress sensitivity: PSI

Complicated Grief Treatment (CGT) BEHAVIORAL

CAU plan modified to include a trial of CGT.

Grief: PSI

Care as usual (CAU) plan OTHER

Unmodified CAU plan.

Anhedonia phenotype: CAU; Anxious distress: CAU; Cognitive deficits: CAU; Grief: CAU; Stress sensitivity: CAU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is able to provide informed consent
• English speaker
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

Nancy Friend Pritzker Psychiatry Building, University of California, San Francisco

San Francisco, California, 94107, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Pramipexole; Methylphenidate; Phenelzine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Hydrazines

Study Officials

• Andrew D. Krystal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2024
• First Posted: August 30, 2024
• Study Start: November 12, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)