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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of Adderall XR, a medication commonly used for ADHD, when combined with brain stimulation therapy for Major Depressive Disorder. The researchers aim to determine if Adderall XR enhances the therapy's effects. Participants will be randomly assigned to receive either the real medication or a placebo (a sugar pill with no active ingredients) and will continue their current depression treatments, excluding certain stimulants or sedatives. The trial seeks individuals diagnosed with major depression who have not found success with two different antidepressants. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking insights.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Adderall XR, a long-lasting form of amphetamine, is generally safe for adults at doses up to 20 mg per day. The FDA has approved it for treating conditions like ADHD (attention-deficit/hyperactivity disorder). Studies examining similar stimulants have found them to be well-tolerated without serious side effects.

However, some individuals might experience side effects, such as mood changes or feelings of depression, particularly with long-term or high-dose use. Overall, the safety is considered acceptable for short-term use at recommended doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Researchers are excited about using Adderall XR for depression because it introduces a new approach by combining a stimulant medication with Transcranial Magnetic Stimulation (TMS), a non-invasive brain stimulation technique. Unlike typical antidepressants that often take weeks to show effects, this combination has the potential to provide quicker relief by enhancing brain activity more directly. Additionally, Adderall XR might help improve energy and focus in depressed patients, which are areas where standard treatments like SSRIs or SNRIs may fall short.

What evidence suggests that Adderall XR combined with TMS might be an effective treatment for depression?

Research has shown that Adderall XR, a type of medication, might improve depression symptoms when combined with brain stimulation therapy. In this trial, participants will receive either Adderall XR or a placebo at random. In some past cases, patients experienced significant relief from depression when Adderall was added to their treatment. Although primarily used for ADHD, Adderall XR's stimulating effects might also enhance mood. However, limited evidence exists for its specific use in treating depression. Early signs suggest potential benefits, but further research is necessary to confirm this. ^{6 7 8 9 10}

Who Is on the Research Team?

scott wilke, MD

Principal Investigator

UCLA Semel

Are You a Good Fit for This Trial?

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.

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

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Dextroamphetamine-Amphetamine Augmentation in the ... This patient has recently experienced significant relief of her depressive symptoms using amphetamine and dextroamphetamine (Adderall) as an adjunct to her ...

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK507808/

Dextroamphetamine-Amphetamine - StatPearls - NCBI - NIH Both immediate-release and sustained-release amphetamine medications are FDA-approved for treating attention-deficit hyperactivity disorder ( ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/14737175.2024.2321921

A review of amphetamine extended release once-daily ... MAS XR treatment was also noted to significantly improve symptoms compared to the patients baseline stimulant regimens (p < 0.0001). In ...

4. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-06446-z

Extended-release amphetamine (Dyanavel XR) is associated ... The present analysis found that patients who were taking Dyanavel XR whose anxiety improved and ADHD symptomatology worsened over 90 days were ...

5. withpower.com withpower.com/trial/early-phase-1-depressive-disorder-8-2021-dfb33

Adderall XR + TMS for Depression (Stimulant-rTMS Trial) This study analyzes the affects or Adderall extended-release (XR) in Subjects receiving brain stimulation therapy for the treatment of Major Depressive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2670101/

Potential Adverse Effects of Amphetamine Treatment on Brain ... For adults, Adderall XR is approved at doses up to 20 mg per day, due to lack of evidence for clearly superior benefits from higher doses.

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833773

Safety of Stimulants Across Patient Populations: A Meta- ... In adults, 27 trials of methylphenidate, including XR and OROS formulations, found the stimulant to be safe, with no reports of serious ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10533622/

A meta-analytic review of the impact of ADHD medications ... In the placebo groups, 15% of participants were rated as having depression as a side effect. Overall, there was no significant difference in depression side ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/021303s038lbl.pdf

Adderall XR - accessdata.fda.gov Safety data on all patients are included in the discussion that follows. Adverse reactions were assessed by collecting adverse reactions, results of ...

10. charliehealth.com charliehealth.com/areas-of-care/depression/can-adderall-cause-depression

Can Adderall Cause Depression? While this boost can enhance focus and energy in the short term, chronic use or high doses can lead to neurotransmitter depletion and dysregulation over time.