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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if a device that sends small electrical pulses to the brain can help teenagers with ADHD improve their memory and attention. The treatment targets a specific brain area to make brain waves work better together.

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 data supports the effectiveness of the treatment Intermittent Theta Burst Stimulation for ADHD?

Research shows that Intermittent Theta Burst Stimulation (iTBS) has shown promise in treating depression by targeting brain areas involved in mood regulation. While this is not directly about ADHD, it suggests that iTBS can influence brain activity, which might be beneficial for ADHD symptoms. ^{1 2 3 4 5}

Is theta burst stimulation safe for humans?

Theta burst stimulation (TBS), including intermittent theta burst stimulation (iTBS), has been studied for safety in both adults and children. While generally considered safe, some people may experience tolerability issues, such as discomfort during treatment. ^{1 2 6 7 8}

How does the treatment Intermittent Theta Burst Stimulation (iTBS) for ADHD differ from other treatments?

Intermittent Theta Burst Stimulation (iTBS) is a unique treatment that uses magnetic pulses to stimulate the brain, specifically targeting the left dorsolateral prefrontal cortex, which is different from traditional medication-based treatments for ADHD. This method is non-invasive and has been shown to be effective in treating depression, suggesting potential benefits for ADHD as well. ^{1 8 9 10 11}

Eligibility Criteria

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

13-18 years

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. Netherlands 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. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Assessing the Effects of Continuous Theta Burst Stimulation Over the Dorsolateral Prefrontal Cortex on Human Cognition: A Systematic Review. [2020]

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

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. [2016]

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

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. [2022]

6. Netherlands 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. [2023]

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

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]

9. England pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. [2023]

10. United States 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). [2022]

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

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. [2021]