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

150 Participants Needed

Trial Summary

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 data supports the effectiveness of the drugs used in the Precision Care for Depression trial?

The drugs like methylphenidate (found in Ritalin and Concerta) have been shown to effectively manage symptoms of attention-deficit/hyperactivity disorder (ADHD) by reducing inattention and hyperactivity. Although these studies focus on ADHD, the effectiveness of methylphenidate in improving focus and attention could potentially benefit patients with depression who experience similar symptoms. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Methylphenidate, used in various forms for ADHD, has been studied for safety in children and adults. Common side effects include decreased appetite, weight loss, and insomnia, but serious side effects are rare. Overall, it is considered safe and well-tolerated when used as prescribed. ^{6 7 8 9 10}

What makes the drug CGT, MBSST, Methylphenidate, Phenelzine, Pramipexole unique for treating depression?

This treatment is unique because it combines multiple drugs, including Methylphenidate and Pramipexole, which are typically used for other conditions like ADHD and Parkinson's disease, respectively. This combination approach may offer a novel way to address depression by targeting different pathways in the brain. ^{11 12 13 14 15}

What is the purpose of this trial?

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.

Research Team

Andrew Krystal, MD, MS

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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: Stress sensitivity: CAU Active Control 1 Intervention

Group VII: Grief: CAU Active Control 1 Intervention

Group VIII: Cognitive deficits: CAU Active Control 1 Intervention

Group IX: Anhedonia phenotype: 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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Not All Generic Concerta Is Created Equal: Comparison of OROS Versus Non-OROS for the Treatment of ADHD. [2017]

2. Germany 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. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. New Zealand 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Medication Persistence, Duration of Treatment, and Treatment-switching Patterns Among Canadian Patients Taking Once-daily Extended-release Methylphenidate Medications for Attention-Deficit/Hyperactivity Disorder: A Population-based Retrospective Cohort Study. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of attention-deficit/hyperactivity disorder medications in children: an intensive pharmacosurveillance monitoring study. [2015]

7. France pubmed.ncbi.nlm.nih.gov

[Utilization of methylphenidate(Ritalin) in France]. [2013]

8. United States 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. [2021]

9. United States 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. [2022]

10. United States 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. [2023]

11. Greece pubmed.ncbi.nlm.nih.gov

Clinical implementation of preemptive pharmacogenomics in psychiatry: Τhe "PREPARE" study. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Integrated pharmacokinetics and pharmacodynamics of the novel catechol-O-methyltransferase inhibitor tolcapone during first administration to humans. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Paroxetine for the treatment of depression: a critical update. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Comparisons of the efficacy and tolerability of extended-release venlafaxine, mirtazapine, and paroxetine in treatment-resistant depression: a double-blind, randomized pilot study in a Chinese population. [2018]

15. England pubmed.ncbi.nlm.nih.gov

No difference in adherence to paroxetine between depressed patients with early remission and those with late remission based on monitoring of plasma paroxetine concentrations. [2022]