Brain Stimulation for ADHD

Overseen By Brian C Kavanaugh, PsyD ABPP

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Bradley Hospital

Must not be taking: Seizure threshold reducers

Disqualifiers: Epilepsy, Seizures, Substance abuse, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a non-invasive technique called brain stimulation can improve symptoms of ADHD, a condition affecting focus and behavior, in teenagers. The method involves applying intermittent Theta Burst Stimulation, a type of brain stimulation therapy, to a specific part of the brain over several sessions. The trial compares the effects of actual brain stimulation to a sham version to assess any real benefits. Teens aged 12-18 with a confirmed ADHD diagnosis who can maintain stable ADHD treatments may be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new ADHD treatments.

Will I have to stop taking my current medications?

You can continue your current ADHD treatments, but you cannot make any changes to them during the study. If you need to change your treatment, it might lead to leaving the study.

What prior data suggests that this brain stimulation technique is safe for adolescents with ADHD?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe for treating ADHD. Many participants in studies tolerate iTBS well, and it may help improve ADHD symptoms. In one study, 75% of participants noticed better ADHD symptoms after 10 days of treatment. Another study found that most participants experienced significant improvement, with some having periods without symptoms. These findings suggest that iTBS is promising and well-tolerated.

While these results are encouraging, individual experiences can vary. Some people might experience side effects, but serious ones are uncommon according to these studies. Consulting a healthcare provider about any concerns before joining a clinical trial is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about intermittent Theta Burst Stimulation (iTBS) for ADHD because it offers a non-invasive and potentially faster-acting alternative to traditional treatments like medications and behavioral therapy. Most ADHD treatments rely on altering neurotransmitter levels through medication, which can take weeks to show effects and may have side effects. In contrast, iTBS targets the brain directly by stimulating the left dorsolateral prefrontal cortex, potentially enhancing brain function and improving attention more quickly. This method could provide a quicker, side-effect-free option, giving new hope to those who don't respond well to standard treatments.

What evidence suggests that intermittent Theta Burst Stimulation could be effective for ADHD?

Research has shown that a treatment called intermittent theta burst stimulation (iTBS) may help with ADHD. In this trial, participants will be assigned to different treatment arms. One group will receive active iTBS, which previous studies have shown to reduce ADHD symptoms in 75% of people after 10 days of treatment. Specifically, one study found that 79% of participants no longer showed symptoms after ten sessions each day for five days. These results suggest that iTBS could effectively manage ADHD by targeting brain areas related to attention and impulse control. Meanwhile, another group in this trial will receive sham iTBS as a comparator. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for teenagers aged 13-18 with ADHD, an IQ over 80, and specific working memory challenges. They must have a clinical diagnosis of ADHD confirmed by the NICHQ Vanderbilt Assessment Scales-Parent and be fluent in English. Participants can continue their current ADHD treatments but cannot change them during the study.

Inclusion Criteria

Your IQ (intelligence quotient) should be higher than 80.

Parent rating on BRIEF-2 Working Memory: Greater than 1.0 SD above normative mean

Clinical diagnosis of attention deficit hyperactivity disorder (ADHD): predominantly inattentive type, predominantly hyperactive/impulsive type, combined type, or unspecified type. Diagnostic criteria will be confirmed with NICHQ Vanderbilt Assessment Scales-Parent.

Exclusion Criteria

You have a pacemaker.

Contraindicated metal implants in the head, brain or spinal cord (excluding dental implants, braces or fillings)

Non-removable makeup or piercings

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a two-week course of active and sham iTBS to the left DLPFC

4 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment with more iTBS sessions

10-20 days

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta Burst Stimulation to the Left Dorsolateral Prefrontal Cortex

Trial Overview The trial tests Intermittent Theta Burst Stimulation to the Left Dorsolateral Prefrontal Cortex on teens with ADHD. It aims to see if this non-invasive brain stimulation can improve symptoms by affecting brain activity related to attention and impulsivity.

How Is the Trial Designed?

Group I: Active intermittent Theta Burst Stimulation Active Control 1 Intervention

Participants will complete 10 daily sessions of active iTBS to the left dorsolateral prefrontal cortex

Group II: Sham intermittent Theta Burst Stimulation Placebo Group 1 Intervention

Participants will complete 10 daily sessions of sham iTBS to the left dorsolateral prefrontal cortex

Intermittent Theta Burst Stimulation to the Left Dorsolateral Prefrontal Cortex is already approved in United States, European Union for the following indications:

Approved in United States as iTBS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)

Approved in European Union as iTBS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)

Who Is Running the Clinical Trial?

Bradley Hospital

Lead Sponsor

Trials

22

Recruited

1,900+

Published Research Related to This Trial

In a study of 71 participants with Major Depressive Disorder who had limited response to high-frequency left-sided stimulation, subthreshold intensity intermittent theta-burst stimulation priming (iTBS-P) led to a greater reduction in depressive symptoms compared to suprathreshold intensity stimulation.

The results suggest that iTBS-P may work through homeostatic plasticity mechanisms, indicating that lower intensity stimulation could be more effective for clinical improvement in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. Lee, JC., Corlier, J., Wilson, AC., et al.[2021]

Theta burst stimulation (TBS) appears to be safe and tolerable for children and adolescents, with reported adverse events mostly being mild, such as headaches, similar to those seen in adults.

Despite the promising safety profile, there is a lack of long-term studies on TBS in younger populations, highlighting the need for further research to better understand its effects and potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. Elmaghraby, R., Sun, Q., Ozger, C., et al.[2023]

Intermittent theta-burst stimulation (iTBS) significantly improves hand function in stroke patients, particularly in those with higher baseline motor function and the presence of motor-evoked potentials (MEPs).

The study of 72 stroke patients showed that those with MEPs and better grip strength (Group A) had the greatest improvement in motor function, suggesting that iTBS effectiveness can be predicted by these factors, allowing for more tailored neurostimulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. Lai, CJ., Wang, CP., Tsai, PY., et al.[2016]

In a study of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

Bilateral theta-burst stimulation (TBS) significantly improved depressive symptoms and remission rates in patients with major depressive disorder (MDD), showing a response rate of 55.1% compared to 20.3% for sham stimulation across six randomized controlled trials involving 285 participants.

The treatment was well-tolerated, with similar rates of discontinuation and adverse events (like headache and dizziness) between the TBS and sham groups, indicating its safety as an intervention for mood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral theta burst stimulation for patients with acute unipolar or bipolar depressive episodes: A systematic review of randomized controlled studies. Qin, ZJ., Huang, SQ., Lan, XJ., et al.[2023]

Continuous theta burst stimulation (cTBS) effectively inhibits synaptic transmission in the primary motor cortex for up to 1 hour, demonstrating its potential as a novel neuromodulation technique.

cTBS applied to the left motor cortex increases local GABA levels, indicating enhanced GABAergic activity, while not significantly affecting glutamate/glutamine levels, suggesting a specific mechanism of action for this stimulation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. Stagg, CJ., Wylezinska, M., Matthews, PM., et al.[2022]

Continuous theta burst stimulation (cTBS) was found to be safe and well-tolerated in patients with major depressive disorder (MDD) or bipolar depression (BD), with no significant differences in adverse events compared to sham treatment.

However, the meta-analysis of three randomized controlled trials involving 78 participants showed no significant improvement in depression scores or response rates with cTBS compared to sham, indicating that cTBS may not provide a therapeutic advantage for treating major depressive episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. Cai, DB., Qin, XD., Qin, ZJ., et al.[2023]

A clinical trial involving 96 outpatients with moderate depression will investigate the effectiveness of intermittent theta burst stimulation (iTBS) on reducing depressive symptoms, comparing it to a sham treatment over ten sessions.

The study will also explore various factors, including genetic and neuropsychological measures, that may influence the response to iTBS, ensuring a thorough safety screening and adherence to ethical guidelines throughout the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. Ørbo, MC., Grønli, OK., Larsen, C., et al.[2023]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

In a randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

Continuous theta burst stimulation (cTBS) over the dorsolateral prefrontal cortex generally impairs cognitive performance in areas such as attention, planning, and decision-making, based on a review of 25 studies involving both healthy participants and those with treatment-resistant depression.

However, cTBS can also enhance cognitive performance by reducing impulsivity and the influence of distractions, indicating a complex relationship between stimulation and cognitive processes depending on the specific brain region targeted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the Effects of Continuous Theta Burst Stimulation Over the Dorsolateral Prefrontal Cortex on Human Cognition: A Systematic Review. Ngetich, R., Zhou, J., Zhang, J., et al.[2020]

Citations

1. medrxiv.org medrxiv.org/content/10.1101/2025.09.03.25335033v1

Intermittent theta burst stimulation for attention deficit ... Intermittent theta burst stimulation for attention deficit hyperactivity disorder ... iTBS holds promise as a potential future treatment for ADHD ...

2. medrxiv.org medrxiv.org/content/10.1101/2025.09.03.25335033v1.full-text

Intermittent theta burst stimulation for attention deficit ... Following 10 days of twice daily iTBS, three out of four (75%) participants experienced categorical ADHD symptom response and also ADHD symptom ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07084649

NCT07084649 | Dual-target iTBS for Youth With ADHD Phase 1: A randomized, double-masked, controlled trial that will rigorously validate the efficacy and safety of dual-target aiTBS for youth with ADHD.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11238064/

Accelerated Intermittent Theta-Burst Stimulation and ... Ten sessions per day for 5 days achieved 79% remission in a sham-controlled randomized clinical trial—substantially better than remission rates ...

5. researchgate.net researchgate.net/publication/395485552_Intermittent_theta_burst_stimulation_for_attention_deficit_hyperactivity_disorder

Intermittent theta burst stimulation for attention deficit ... Classical psychedelic drugs show promise as a treatment for major depressive disorder and related psychiatric disorders. This therapeutic ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06010966

NCT06010966 | Effect of iTBS on Children With ADHD This project uses the iTBS stimulation on weekends, children with ADHD finish scale evaluation, magnetic resonance imaging analysis, and cognitive function ...