RNA Editing as a Biomarker of Antidepressant Response in Unipolar and Bipolar Depression (EDIT-ANDRE)

The purpose of this research is to understand how changes in RNA editing relate to treatment response in unipolar and bipolar depression.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Depression; Unipolar Depression
• Intervention / Treatment: Drug: Vortioxetine; Drug: Cariprazine (Augmentation Phase)

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Scott E. Feeder; Phone Number: 507-255-1975; Email: feeder.scott@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Scott E. Feeder; Phone Number: 507-255-1975
      • Principal Investigator: Aysegul Ozerdem, MD, PhD
      • Principal Investigator: Deniz Ceylan, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

Participants must meet all the following criteria to be eligible for the study:

1. Adult females and males, aged 18-65 years
2. Must have the capacity to understand study procedures, to comply with them for the entire length of the study, and to provide informed consent.
3. Current major depressive episodes associated with MDD, BD-I, or BD-II, confirmed using the SCID-IV-CV. If a participant has already completed a structured diagnostic interview within the last 2 years or participated in any of the following studies and provided consent to use their information in future studies: (IRB 19-001722, IRB: 23-004500, IRB: 24-013228, IRB: 25-005856, IRB: 25-007244), those SCID results can be used for the EDIT-ANDRE study.
4. Symptom severity score on the Quick Inventory for Depressive Symptomatology - Clinician (QIDS-C16) > 10.
5. Ability to travel for assessment visits.
6. Negative urine pregnancy test for people of childbearing potential
7. People of childbearing potential must be using an acceptable method of birth control during the study, such as hormonal contraception, intrauterine device, bilateral tubal ligation, partner's documented vasectomy, or complete abstinence from intercourse with childbearing potential, with barrier methods permitted only when used in combination with one of these primary methods.
8. BD-I patients must be on stable dose of at least one mood stabilizer (i.e., lithium, valproate, or a mood-stabilizing atypical antipsychotic at least for one month) at the time of enrollment.

Patients with BD-II who enroll in the study while currently taking a mood stabilizer (including lithium, valproate, or lamotrigine) must have been on a stable dose of that medication for a minimum of one month before enrollment.

Exclusion Criteria

All candidates meeting any of the following criteria at baseline will be excluded from study participation:

1. Individuals who cannot understand English will not be enrolled because informed consent, study procedures, and interviews require comprehension of English.
2. Inability to provide written, voluntary informed consent due to but not limited to being under conservatorship, guardianship, commitment, or currently undergoing involuntary psychiatric hospitalization.
3. Failure to score at least 75% on a 4-item comprehension assessment related to study goals, risks, and benefits
4. For BD-I: not having used at least one mood stabilizer (e.g., lithium, valproate, or mood-stabilizing antipsychotics) at a stable dose and within a therapeutically effective antimanic range for a minimum of one month.
5. History of treatment-refractory depression, defined as non-response to two or more antidepressant or mood-stabilizing regimens despite adequate dose, duration, and adherence during the current episode.
6. Participants with active suicidal ideation, defined as a MADRS item #10 score greater than 4 or a "yes" response to item #4 (ideation with intent) or item #5 (ideation with plan) on the C-SSRS, will be excluded
7. A medically serious suicide attempt within the past 6 months, defined as requiring emergency department evaluation, a medical procedure, or admission to a hospital (e.g., internal medicine, cardiology, or ICU)
8. Current use of monoamine oxidase inhibitors or use within 14 days following discontinuation of a monoamine oxidase inhibitor
9. Presence of mixed symptoms of depression, defined as a YMRS score ≥12
10. Current use of any of the study medications (e.g., vortioxetine, or cariprazine) at the time of enrollment (previous use of these medications is acceptable)
11. Prior hypersensitivity reaction to any of the study medications or documented non-response to any of the study medications at the maximum therapeutic dose
12. A history of seizure disorder
13. Recent use of long half-life psychotropic medications, including fluoxetine (in patients with BD and MDD) and long acting injectable forms of antipsychotics (mainly in BD II and MDD) within the past 4 weeks.
14. Active psychosis, defined as a YMRS item #8 score >4 or diagnosis of schizophrenia, schizoaffective disorder, delusional disorder, or schizophreniform disorder as determined by structured clinical interview
15. Current drug or alcohol use disorder (excluding nicotine); full remission for at least 3 months is required for eligibility
16. Positive toxicology screen for illicit substances (e.g., cocaine, methamphetamine, illegal opiates). Participants who use cannabis for recreational or medicinal purposes and fail the toxicology screen can potentially be included in the study only if they take the CUDIT-R and score a 12 or less.
17. Individuals who are pregnant, lactating, trying to conceive, or not using adequate contraception (e.g., hormonal contraception, intrauterine device, tubal ligation, or condoms)
18. Any active or unstable medical condition judged by the principal investigator to confer excessive risk
19. Clinically significant laboratory abnormality, uncontrolled hypertension (blood pressure >160/100 mmHg), or tachycardia (heart rate >110 bpm)
20. Significant renal, hepatic, or cardiac disease; malignancy; autoimmune disease; or chronic kidney disease > stage IIIa (estimated GFR < 60 mL/min/1.73 m²)
21. History of traumatic brain injury defined as loss of consciousness for 5 minutes and related to a trauma event
22. Gastric bypass, specifically Roux-en-Y
23. Clinical current diagnosis of delirium, encephalopathy, intellectual disability or cognitive disorder (mild or major neurocognitive disorder)
24. Currently receiving electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), or deep brain stimulation (DBS) as acute or maintenance treatment
25. Current use of systemic steroids, chemotherapy, and radiotherapy
26. Daily use of lorazepam (Ativan) >4 mg/day, or equivalent doses of other benzodiazepines (e.g., clonazepam >1 mg, alprazolam >2 mg, diazepam >20 mg)
27. No access to smartphones, internet
28. Other Axis I or II diagnoses, by clinical judgments that are the current reason for treatment evaluation or play a large part of the current symptom presentation
29. Ongoing treatment with opioid agonists will constitute an exclusion criterion. In contrast, other ongoing treatments, such as alcohol relapse prevention agents or ADHD pharmacotherapy, will not be considered exclusion criteria, provided that no treatment initiation or significant dose adjustment has occurred within the past 4 weeks.

All candidates meeting any of the following criteria at baseline will be excluded from the Phase 2 (cariprazine add-on) of the study:

1. Meeting symptomatic remission criteria based on MADRS (≤ 10).
2. Current use of a strong or moderate CYP3A4 inhibitor (e.g., ketoconazole, clarithromycin, fluconazole, or verapamil) strong or moderate CYP3A4 inducer (e.g., carbamazepine, rifampin, phenytoin, or St. John's Wort), due to potential pharmacokinetic interactions with cariprazine.
3. Diagnosis of BD-I with concurrent use of an antipsychotic agent as a mood stabilizer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vortioxetine; Subjects will be started on vortioxetine for 8 weeks of treatment with vortioxetine at 10 mg/day, titrated to 20 mg/day (after 7 days). Subjects who do not meet remission criteria will enter a second 8 week augmentation phase.	Drug: Vortioxetine; Vortioxetine, once daily, for 8 weeks; Drug: Cariprazine (Augmentation Phase); Participants who do not meet remission criteria will enter a second 8-week augmentation phase (Weeks 9-16). During this phase, cariprazine will be added to the existing regimen, administered orally once daily in the morning, starting at 1.5 mg/day and titrated up to 3.0 mg/day in one week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score	The Montgomery-Åsberg Depression Rating Scale (MADRS) is scored on a scale of 0 to 60, with each of the 10 items rated from 0 to 6 by a trained clinician during an interview. A higher score indicates a more severe level of depression, with common severity ranges being: 0-6 (normal), 7-19 (mild), 20-34 (moderate), and 35-60 (severe).	Baseline, Week 2, Week 8, Week 10, Week 16

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Aysegul Ozerdem, MD, PhD, Mayo Clinic; Principal Investigator: Deniz Ceylan, MD, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: November 25, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Depressive Disorder; Bipolar Disorder; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Vortioxetine; cariprazine
• Other Study ID Numbers: 25-006875

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