Precision Care for Depression

Overseen By Ethan G. Dutcher, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Disqualifiers: Unstable conditions, Suicidal risk, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether selecting depression treatments based on specific symptoms, such as extreme sadness or anxiety, is more effective than the usual method. It includes various treatments like Cognitive Group Therapy (CGT), Mindfulness-Based Stress and Self-Compassion Training (MBSST), and medications such as methylphenidate (a stimulant) and phenelzine (an antidepressant). The trial is open to English-speaking adults diagnosed with major depressive disorder who match at least one of the study's specialized symptom profiles. Participants should also have a baseline PHQ-8 score of 10 or higher, indicating moderate to severe depression. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, and this research aims to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What is the safety track record for these treatments?

Research shows that the treatments in this trial have varying safety levels for individuals.

Cognitive-behavioral therapy (CBT), including a type called CGT, is well-researched and considered safe for many mental health issues, such as depression. Studies have found it to be an effective first choice with few risks.

Mindfulness-based stress reduction (MBSST) is also generally safe. Research indicates it helps reduce emotional distress and improve mood without major side effects.

Methylphenidate, often used for ADHD and sometimes for depression, is safe when used properly, though it can cause side effects like trouble sleeping or a faster heartbeat.

Phenelzine, an antidepressant for treatment-resistant depression, works well but may cause side effects like restlessness or mood changes. Monitoring for these effects is important.

Pramipexole, usually used for Parkinson's disease and sometimes for depression, can be safe for short-term use, but it may cause dizziness or sleepiness.

Overall, these treatments have been tested for safety, but they can have side effects. Participants should discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for depression target neurotransmitters like serotonin or norepinephrine. But this trial is exciting because it explores a range of diverse approaches, including novel therapies like Cognitive Behavioral Therapy (CBT) tailored for specific phenotypes such as anxiety and anhedonia, and medications like Pramipexole, which targets dopamine pathways. Unlike standard antidepressants that often take weeks to show effects, Pramipexole may provide quicker relief by acting on dopamine receptors, which are linked to motivation and pleasure. Additionally, Methylphenidate, commonly used for ADHD, is being investigated for its potential to enhance focus and energy levels in depression. Researchers hope these varied approaches will offer more personalized and effective treatment options for individuals with different depression profiles.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that Cognitive Behavioral Therapy (CBT) effectively treats depression. Studies support its use, and it is often recommended as a first choice for treating depression. In this trial, participants may receive different treatments, including CBT and MBSST.

Mindfulness-Based Stress Reduction Therapy (MBSR) has been found to slightly help with depression and moderately help with anxiety, making it a good option for improving emotional well-being. This trial will evaluate MBSST, a related approach.

Methylphenidate, one of the treatments under study in this trial, has shown effectiveness when added to other depression treatments, especially for people with bipolar disorder, with 44% showing significant improvement in studies.

Phenelzine, another treatment option in this trial, has successfully treated different types of depression, including atypical depression. Some studies suggest it may be more effective than other treatments in certain cases.

Pramipexole, also being studied in this trial, has been shown to help with depression symptoms, particularly in people with Parkinson's disease and those whose depression hasn't improved with other treatments, when used alongside other antidepressants. ^{2 6 7 8 9}

Who Is on the Research Team?

Andrew Krystal, MD, MS

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for individuals with major depressive disorder who are seeking new treatment options. Participants should be diagnosed with depression and willing to try different therapies such as mindfulness, medication, or standard care.

Inclusion Criteria

Participant is able to provide informed 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

Exclusion Criteria

Significant risk of suicidal or violent behavior as determined by clinical judgement

Unstable or untreated medical or psychiatric condition based on clinical assessment by investigator(s)

Pregnant or breastfeeding or planning to become pregnant during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phenotyping

Participants are classified into one of five phenotypes: Anhedonia, Cognitive deficits, Stress sensitivity, Anxious distress, and Grief

1-2 weeks

Treatment

Participants receive phenotype-specific intervention (PSI) or care as usual (CAU) for depression

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Care as usual (CAU) plan
• CGT
• MBSST
• Methylphenidate
• Phenelzine
• Pramipexole

Trial Overview

The study tests if choosing treatments based on individual characteristics (phenotyping) is better than usual selection methods for depression. Therapies include Mindfulness-based Stress Sensitivity Therapy, medications like Pramipexole and Phenelzine, and standard care.

How Is the Trial Designed?

Group I: Stress sensitivity: PSI Experimental Treatment 1 Intervention

Group II: Grief: PSI Experimental Treatment 1 Intervention

Group III: Cognitive deficits: PSI Experimental Treatment 1 Intervention

Group IV: Anxious distress: PSI Experimental Treatment 1 Intervention

Group V: Anhedonia phenotype: PSI Experimental Treatment 1 Intervention

Group VI: Anhedonia phenotype: CAU Active Control 1 Intervention

Group VII: Stress sensitivity: CAU Active Control 1 Intervention

Group VIII: Grief: CAU Active Control 1 Intervention

Group IX: Cognitive deficits: CAU Active Control 1 Intervention

Group X: Anxious distress: CAU Active Control 1 Intervention

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a study involving 76 children with ADHD, the intensive pharmacosurveillance program revealed that atomoxetine (ATX) and methylphenidate (MPH) are generally safe, with most adverse drug reactions (ADRs) being common, non-serious, and fully resolved, although weight loss was the most frequently reported ADR.

The program also identified some unexpected ADRs, such as hepatomegaly and suicidal ideation, highlighting the importance of ongoing monitoring to ensure drug safety in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of attention-deficit/hyperactivity disorder medications in children: an intensive pharmacosurveillance monitoring study. Ruggiero, S., Rafaniello, C., Bravaccio, C., et al.[2015]

Tolcapone, a novel COMT inhibitor, was well tolerated in healthy volunteers across a wide range of doses (5 to 800 mg) without significant adverse effects or changes in vital signs.

The drug effectively inhibited COMT activity in erythrocytes by over 80% at doses of 200 mg and higher, demonstrating dose-proportional pharmacokinetics and a rapid onset of action, suggesting its potential for further study in treating Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated pharmacokinetics and pharmacodynamics of the novel catechol-O-methyltransferase inhibitor tolcapone during first administration to humans. Dingemanse, J., Jorga, KM., Schmitt, M., et al.[2018]

The study involved 119 preschool children aged 4 to <6 years with ADHD, showing that the methylphenidate hydrochloride extended-release capsule (MPH-MLR) significantly reduced ADHD symptoms, with mean ADHD-RS-IV scores dropping from 40.8 to 19.5 during the open-label phase.

In a double-blind phase, children receiving MPH-MLR had a significantly greater improvement in ADHD symptoms compared to those on placebo, with common side effects including decreased appetite and insomnia, consistent with known effects of methylphenidate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Preschool Children with Attention-Deficit/Hyperactivity Disorder. Childress, AC., Kollins, SH., Foehl, HC., et al.[2021]

In a 1-year study involving 282 children aged 6-12 with ADHD, SDX/d-MPH was found to be safe and well tolerated, with 60.1% of participants experiencing treatment-emergent adverse events, mostly mild to moderate.

The treatment led to significant reductions in ADHD symptoms, demonstrating sustained efficacy over the year, comparable to other methylphenidate products, with no unexpected safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study. Childress, AC., Marraffino, A., Cutler, AJ., et al.[2023]

In a study involving children aged 6-12 years with ADHD, once-daily modified-release methylphenidate (EqXL) was found to be non-inferior to twice-daily immediate-release methylphenidate (MPH-IR) in reducing ADHD symptoms over three weeks.

Both formulations of methylphenidate were significantly more effective than placebo, and all treatments were well tolerated, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder. Findling, RL., Quinn, D., Hatch, SJ., et al.[2018]

Dexmethylphenidate, a chirally pure form of methylphenidate, has been shown to effectively manage ADHD in children at half the dose of traditional Ritalin, based on clinical trials involving 684 children.

The drug works by inhibiting the reuptake of norepinephrine and dopamine, and has been found to be well tolerated, with ongoing research to further understand its therapeutic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate--Novartis/Celgene. Focalin, D-MPH, D-methylphenidate hydrochloride, D-methylphenidate, dexmethylphenidate, dexmethylphenidate hydrochloride. [2018]

In a post hoc analysis of a phase III study involving 336 children and adolescents with ADHD, lisdexamfetamine demonstrated significantly greater improvement in ADHD symptoms compared to osmotic-release oral system methylphenidate (OROS-MPH), with a mean change in ADHD-RS-IV total score of -24.3 for lisdexamfetamine versus -18.7 for OROS-MPH.

While lisdexamfetamine was more effective, it also had a higher incidence of treatment-emergent adverse events, such as decreased appetite and insomnia, compared to OROS-MPH, indicating that both medications have safety profiles typical of stimulant treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post hoc comparison of the effects of lisdexamfetamine dimesylate and osmotic-release oral system methylphenidate on symptoms of attention-deficit hyperactivity disorder in children and adolescents. Soutullo, C., Banaschewski, T., Lecendreux, M., et al.[2021]

A review of the French Pharmacovigilance database revealed 21 reported adverse drug reactions related to methylphenidate, with 16 cases suspected to be linked to the medication; these were mostly mild and resolved quickly.

The findings indicate that there is no evidence of methylphenidate misuse or overuse among the 1300 to 4000 children treated in France, supporting the need for continued strict prescription regulations to prevent potential misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Utilization of methylphenidate(Ritalin) in France]. Frances, C., Hoizey, G., Millart, H., et al.[2013]

In a 7-week study involving 226 adults with ADHD, OROS methylphenidate significantly improved ADHD symptoms compared to placebo, as shown by lower scores on the Adult ADHD Investigator Symptom Report Scale.

The treatment was well tolerated, with no serious adverse events reported, and a higher percentage of participants on OROS methylphenidate were classified as responders compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, double-blind, parallel group, dose-escalation study. Adler, LA., Zimmerman, B., Starr, HL., et al.[2022]

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