Adderall XR + TMS for Depression

(Stimulant-rTMS Trial)

Overseen By Nikita Vincecruz, BS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Los Angeles

Must not be taking: Psychostimulants, Benzodiazepines, MAOIs

Disqualifiers: Bipolar, Psychotic disorders, Substance use, others

Compensation: Varies

Number of Visits: 15

Duration: 2 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This study analyzes the affects or Adderall extended-release (XR) in Subjects receiving brain stimulation therapy for the treatment of Major Depressive Disorder. Subjects will be assigned by chance to active or placebo group. Active group will be asked to take one 15 mg pill once daily of Adderall XR (amphetamine) and the Placebo group will be asked take an identical appearing tablet/capsule, one tablet by mouth daily. The placebo tablet has no active ingredients and has no affect on the body or mind. With the exception of the study drug, all other study activities between both groups will be identical. Subjects will use the assigned study drug two weeks before therapy and throughout the first 10 therapy treatments. A total of seven(7) visits will be required for screening, drug assignment, and completion of mood assessments. This study will enroll a total of 30 Subjects.

Will I have to stop taking my current medications?

You can continue taking your current medications during the study, except for psychostimulants, benzodiazepines, and MAOIs (a type of antidepressant) if you have used them in the past two weeks.

What data supports the effectiveness of the treatment Adderall XR + TMS for Depression?

Research shows that transcranial magnetic stimulation (TMS) is effective for treating major depressive disorder, especially in patients who haven't responded to other treatments. While Adderall XR is not specifically mentioned in the studies, TMS has been shown to help with depression, which might support its use in combination with other treatments. ^{1 2 3 4 5}

Is the combination of Adderall XR and TMS safe for humans?

Transcranial magnetic stimulation (TMS) is considered safe and is FDA-approved for treating certain types of depression. Adderall XR, a form of amphetamine, is generally safe when used as prescribed, but common side effects include nausea and decreased appetite. ^{1 2 4 6 7}

How does the treatment Adderall XR + TMS for depression differ from other treatments?

This treatment combines Adderall XR, a medication typically used for ADHD, with transcranial magnetic stimulation (TMS), a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain. The combination is unique because it pairs a stimulant medication with TMS, which is already known for its antidepressant effects, potentially offering a novel approach for those who have not responded to traditional antidepressant medications. ^{1 5 6 8 9}

Research Team

scott wilke, MD

Principal Investigator

UCLA Semel

Eligibility Criteria

This trial is for adults aged 18-65 with Major Depressive Disorder who haven't improved after two different antidepressant treatments. They can be on other psychotropic meds, but not psychostimulants or benzodiazepines. Participants must not have certain mental health conditions, substance misuse history, severe physical health issues like heart disease, glaucoma, hyperthyroidism, or metal in the head.

Inclusion Criteria

I have tried two antidepressants without improvement.

The outside treating psychiatrist must agree that enrollment in the study is safe and acceptable for the subject.

I am between 18 and 65 years old and have been diagnosed with major depression.

Exclusion Criteria

I have a heart structure problem.

You have any metal objects in your head.

I am currently using, or have used an MAOI in the last two weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Pre-Treatment

Participants take Adderall XR or placebo for at least 10 days to assess side effects and establish stable mood before rTMS treatment

2 weeks

2 visits (in-person)

Treatment

Participants receive 10 sessions of rTMS while continuing Adderall XR or placebo

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Adderall-XR
• Placebo

Trial Overview The study tests if Adderall XR (a stimulant medication) helps brain stimulation therapy work better for depression. Half of the participants will get Adderall and half a placebo pill that does nothing. Everyone gets the same brain stimulation treatment over seven visits including mood assessments.

Participant Groups

Group I: Active Active Control 1 Intervention

Subjects randomized to Adderall will take an tablet/capsule by mouth daily.

Group II: Placebo Placebo Group 1 Intervention

Subjects randomized to placebo will take an identical-appearing tablet/capsule and, in order to maintain blinding, will also take one tablet by mouth daily. The placebo substance will be sugar.

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Findings from Research

In an open-label extension study of trans-cranial magnetic stimulation (TMS) involving patients with medication-resistant major depressive disorder, those who previously received sham treatment showed a significant mean reduction in depression scores (MADRS) of -17.0 after 6 weeks of active TMS, with 42.4% achieving a response and 20.0% reaching remission.

Patients who had not responded to initial active TMS also benefited from continued treatment, showing a mean reduction of -12.5 in MADRS scores, with 26.0% responding and 11.0% remitting, indicating that longer courses of TMS may enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the acute treatment of major depressive disorder: clinical response in an open-label extension trial. Avery, DH., Isenberg, KE., Sampson, SM., et al.[2019]

Transcranial magnetic stimulation (TMS) was effective in treating treatment-resistant depression, with a response rate of 50.6% and a remission rate of 24.7% after 6 weeks of treatment in a cohort of 100 patients.

TMS was well tolerated, showing a low discontinuation rate of 3% and no serious adverse events, indicating its safety as an adjunctive treatment for patients who have not responded to other antidepressant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. Connolly, KR., Helmer, A., Cristancho, MA., et al.[2022]

Transcranial magnetic stimulation (TMS) is a safe and effective treatment approved for conditions like treatment-resistant major depressive disorder and obsessive-compulsive disorder, which are common and significantly impact public health.

Despite its effectiveness, many healthcare providers are not familiar with TMS, highlighting the need for better education on its use and benefits, especially for patients with chronic conditions resistant to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation: A Clinical Primer for Nonexperts. Minzenberg, MJ., Yoon, JH.[2021]

The study demonstrated that AMP XR-OS, a new extended-release amphetamine oral suspension, is bioequivalent to Adderall XR, as shown by pharmacokinetic parameters in 42 healthy adult volunteers.

Safety monitoring revealed that the most common side effects were nausea and decreased appetite, indicating that AMP XR-OS has a similar safety profile to Adderall XR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults. Sikes, C., Stark, JG., McMahen, R., et al.[2022]

The new real electro-magnetic placebo (REMP) device effectively simulates the scalp sensations of real repetitive transcranial magnetic stimulation (rTMS) while ensuring that it does not produce any biologically active electric fields, making it a more reliable sham for clinical trials.

In tests, naive subjects were more likely to mistake the REMP-attenuated TMS for real rTMS compared to other sham methods, indicating that the REMP device provides a superior placebo experience, which is crucial for accurately assessing the efficacy of rTMS treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS). Rossi, S., Ferro, M., Cincotta, M., et al.[2021]

References

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

Transcranial magnetic stimulation in the acute treatment of major depressive disorder: clinical response in an open-label extension trial. [2019]

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

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. [2022]

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

Long-term efficacy of repeated daily prefrontal transcranial magnetic stimulation (TMS) in treatment-resistant depression. [2021]

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

Transcranial Magnetic Stimulation: A Clinical Primer for Nonexperts. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Daily left prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: clinical predictors of outcome in a multisite, randomized controlled clinical trial. [2015]

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

The NeuroStar TMS device: conducting the FDA approved protocol for treatment of depression. [2022]

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

A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS). [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation: a novel antidepressive strategy? [2018]