~20 spots leftby Mar 2026

Brain Stimulation for Depression

(RAISE Trial)

MP
Overseen byMarta Peciña, MD, PhD
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Marta Peciña, MD PhD
Must not be taking: Psychiatric medications, Opioid analgesics
Disqualifiers: Pregnancy, Psychotic disorders, Substance dependence, others
No Placebo Group
Prior Safety Data

Trial Summary

What is the purpose of this trial?

The central goal of this application is to demonstrate the causal contribution of reward learning signals (expected values and reward prediction errors \[RPE\]) to antidepressant responses (Aim1) by experimentally manipulating expected values using transcranial magnetic stimulation (TMS) targeting the vmPFC (Aim 2) and μ-opioid striatal RPE signal using pharmacological approaches (Aim 3).

Will I have to stop taking my current medications?

Yes, you will need to stop taking antidepressant medications at least 21 days before the imaging data collection (five weeks for fluoxetine). Additionally, you cannot be taking any psychiatric medications or other potential augmenting agents.

What data supports the effectiveness of the drug Buprenorphine for depression?

Research shows that low doses of Buprenorphine can effectively reduce depressive symptoms and serious suicidal thoughts, even in patients who don't respond to other antidepressants. However, more studies are needed to understand its long-term effects and the best way to use it with other treatments.12345

Is brain stimulation for depression safe for humans?

Buprenorphine, used in various forms for depression and opioid dependence, is generally considered safe and well-tolerated at low doses, though more studies are needed to understand long-term effects. It has been shown to reduce depressive symptoms and is effective in opioid dependence treatment, with some formulations designed to minimize misuse.13678

How does the treatment of brain stimulation with Buprenorphine and Naltrexone for depression differ from other treatments?

This treatment is unique because it combines brain stimulation, which directly targets brain areas involved in mood regulation, with Buprenorphine and Naltrexone, drugs typically used for addiction treatment, potentially offering a novel approach for treatment-resistant depression by addressing both mood and reward system dysfunctions.910111213

Research Team

MP

Marta Peciña, MD, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

Adults aged 18-55 with major depression, who have tried at most one antidepressant without success, can join this trial. They must be fluent in English and off antidepressants for at least 21 days. People with a history of psychotic disorders, substance dependence (except nicotine), or those currently suicidal or on certain psychiatric medications cannot participate.

Inclusion Criteria

I am between 18 and 55 years old, speak English, and can understand and consent to the study.
I have tried only one antidepressant without success, as per the MGH-ATRQ standards.
A score on the Mood and Anxiety Symptom Questionnaire- Anhedonic Depression (MASQ-AD) ≥ 23 (2/3 sample) and MASQ-AD < 23 (1/3 sample) with or without certain anxiety disorders (e.g., generalized anxiety, panic, agoraphobia, social phobia, and specific phobia)
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Exclusion Criteria

I have been on a stable dose of thyroid medication for hypothyroidism for 3 months.
Requiring immediate hospitalization for psychiatric disorder or have an unstable general medical condition (GMC) that will likely require hospitalization or to be deemed terminal (life expectancy < 6 months after study entry)
Currently enrolled in another study, and participation in that study contraindicates participation in this study
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Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TMS sessions and pharmacological interventions to modulate reward learning signals

3 weeks
3 sessions (in-person)

Follow-up

Participants are monitored for changes in BOLD signal during the Antidepressant fMRI Task

3 weeks
3 visits (in-person)

Treatment Details

Interventions

  • Buprenorphine (Opioid Partial Agonist)
  • Naltrexone (Opioid Antagonist)
  • Theta Burst Stimulation (Device)
Trial OverviewThe study tests if stimulating the brain's reward system using TMS and altering opioid signals with buprenorphine/naltrexone can improve depression symptoms. Participants will receive either real treatments or placebos to compare effects.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Oral Placebo Pill + Intramuscular Saline InjectionExperimental Treatment3 Interventions
Inert pill and saline injection that have no inherent power to produce an effect. In the inert pill condition, participants will receive one IM arm injection of saline (1ML) and an oral placebo tablet.
Group II: Naltrexone Oral Tablet + Intramuscular Saline InjectionExperimental Treatment3 Interventions
Naltrexone is thought to strongly block μ-opioid receptors. Oral (pill) opioid antagonist which will be used to modulate reward learning signals to understand placebo effects in participants with depression. In the naltrexone condition, participants will receive one tablet of 50mg Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours) and a saline IM injection.
Group III: Buprenorphine Injection + Oral Placebo PillExperimental Treatment3 Interventions
Buprenorphine is a μ-opioid partial agonist and kappa-opioid antagonist that is used to treat moderate to severe pain and opioid dependence. The intramuscular administered opioid agonist which will be used to modulate reward learning signals to understand placebo effects in patients with depression. In the buprenorphine condition, participants will receive one IM injection of 0.3mg/1ML buprenorphine hydrochloride (Buprenex®. Richmond, VA: Reckitt Benckiser Pharmaceuticals Inc.; 2006) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~6 hours) and an oral placebo tablet.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Marta Peciña, MD PhD

Lead Sponsor

Trials
3
Recruited
210+

Findings from Research

Buprenorphine (BUP) has been found to be an effective and safe treatment option for reducing depressive symptoms, suicidal ideation, and non-suicidal self-injury, particularly in patients with treatment-resistant depression (TRD).
The study highlights the need for further research to explore the long-term effects of BUP and the efficacy of various combinations with other medications, as well as to establish optimal dosing guidelines.
The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review.Serafini, G., Adavastro, G., Canepa, G., et al.[2023]
Buprenorphine, a partial mu-opioid receptor agonist, is an effective and well-tolerated treatment for opioid dependence, comparable to methadone, and can now be prescribed by all physicians in office-based settings due to the Drug Addiction Treatment Act of 2000.
It is available in two formulations: Subutex (buprenorphine only) and Suboxone (buprenorphine with naloxone), but physicians must obtain a special waiver to prescribe it and are limited to 30 patients at a time.
Buprenorphine: a (relatively) new treatment for opioid dependence.Welsh, C., Valadez-Meltzer, A.[2021]
Buprenorphine is a safe and effective treatment for opioid dependence, particularly when combined with naloxone, which reduces its potential for abuse.
New regulations enable certified physicians to prescribe buprenorphine in their offices, significantly improving patient access to this important treatment.
Buprenorphine maintenance: a new treatment for opioid dependence.Collins, GB., McAllister, MS.[2019]

References

The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression and Suicidal Behavior: A Systematic Review. [2023]
Buprenorphine: a (relatively) new treatment for opioid dependence. [2021]
Buprenorphine maintenance: a new treatment for opioid dependence. [2019]
Depression and Buprenorphine Treatment in Patients with Non-cancer Pain and Prescription Opioid Dependence without Comorbid Substance Use Disorders. [2021]
Group medication management for buprenorphine/naloxone in opioid-dependent veterans. [2014]
Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study. [2015]
Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. [2015]
[Prolonged-release buprenorphine formulations: Perspectives for clinical practice]. [2022]
Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. [2021]
Augmentative therapies do not potentiate the antidepressant-like effects of deep brain stimulation in rats. [2021]
Programmed acute electrical stimulation of ventral tegmental area alleviates depressive-like behavior. [2022]
12.United Statespubmed.ncbi.nlm.nih.gov
Deep brain stimulation of the nucleus accumbens core but not shell reduces motivational components of heroin taking and seeking in rats. [2022]
Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. [2023]