rTMS for Depression in Autism
(rTMS-MDD Trial)
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Centre for Addiction and Mental Health
Must not be taking: Benzodiazepines, Anticonvulsants
Disqualifiers: Substance use disorder, Seizures, Pregnancy, others
No Placebo Group
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?The current clinical trial is focused on evaluating the efficacy of rTMS for treatment of depression in youth and young adults (hereafter called transition aged youth, TAY) with autism spectrum disorder (ASD). The motivation to undertake the current efficacy study is driven by: (1) the substantial impact of depression on TAY with ASD (based on prevalence and contribution to disability/impairment); (2) lack of evidence-based treatments for depression in autism (there are no current trials rigorously evaluating any treatment for depression, i.e., psychotherapeutic, pharmacotherapeutic, brain stimulation); (3) rTMS has demonstrated efficacy in non-autistic individuals to improve symptoms of depression and may be better tolerated in youth than medication treatment; (4) a prior pilot rTMS study focused on treatment of executive function deficits in autism indicated that high frequency rTMS delivered using a rigorous randomized control trial (RCT) protocol can be feasibly implemented in TAY with autism, is well tolerated (mild to moderate adverse effects and low drop out), and has the potential to improve symptoms of depression.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you must not have changed your psychotropic medications or increased their dosage in the last 30 days.
What data supports the effectiveness of the treatment for depression in autism?
Research shows that repetitive transcranial magnetic stimulation (rTMS), including theta burst stimulation (TBS), can help reduce symptoms of major depression. Studies have found that these treatments can be effective when used alongside other therapies, like medication and psychotherapy, for people with depression.
12345Is rTMS safe for humans?
Research shows that rTMS, including theta burst stimulation (TBS), is generally safe for humans, with some studies reporting minor tolerability issues in a small number of participants.
12678How is the treatment rTMS for Depression in Autism different from other treatments?
The treatment uses repetitive transcranial magnetic stimulation (rTMS) with a specific pattern called theta burst stimulation (TBS), which targets the brain's prefrontal cortex to help improve depression symptoms. This approach is unique because it uses magnetic fields to stimulate nerve cells, offering a non-invasive alternative to medication and psychotherapy.
12489Eligibility Criteria
This trial is for young adults with autism who are also dealing with depression. They should be fluent in English, able to consent, clinically stable without medication changes for a month, and have an IQ of 70 or above. Those who are actively suicidal, pregnant, have seizures history or recent substance abuse can't participate.Inclusion Criteria
Global Assessment of Function (GAF) scores (≤60) that is sustained over a lead-in period of two weeks AND/OR VABS-III below adequate functioning at baseline assessment.
My mental health treatment hasn't changed in the last 30 days.
Fluent in English
+3 more
Exclusion Criteria
Significantly debilitating medical or neurologic illness, or acute or unstable medical illnesses as determined by study physician
Metal implants or a pace-maker, claustrophobia that would preclude the MRI scan
Actively suicidal (i.e., suicidal ideation with plan and intent) or high risk for suicide as assessed by a study psychiatrist
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive bilateral theta burst stimulation (BL-TBS) to dorsolateral prefrontal cortex (DLPFC) 5 days per week for 6 weeks
6 weeks
30 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
3 visits (in-person)
Participant Groups
The study tests rTMS (a type of brain stimulation) to see if it helps improve depression symptoms in autistic youth. Participants will receive either the real rTMS treatment or a sham (fake) version to compare outcomes in a controlled setting.
2Treatment groups
Active Control
Placebo Group
Group I: Active bilateral theta burst stimulationActive Control1 Intervention
An X100 stimulator with a B65 A/P type coil (Magventure Inc.) will be used. The coil is positioned under MRI guidance using real-time neuronavigation using Brainsight \[x,y,z= -38, 44, 26(left), +38, 44, 26 (right). BL-TBS will be delivered at 90% RMT, corrected for scalp to cortex distance, to targeted left and right DLPFC sites, differing only in stimulation pattern and total number of pulses (triplet 50 Hz bursts, repeated at 200 msec (i.e., 5 Hz); right DLPFC (continuous TBS, cTBS): 120 seconds uninterrupted bursts (total of 600 pulses); left DLPFC (intermittent TBS, iTBS: 2 seconds on and 8 seconds off; 600 pulses per session; total duration of 3 min 9 seconds/hemisphere).
Group II: Sham bilateral theta burst stimulationPlacebo Group1 Intervention
An X100 stimulator with a B65 A/P type coil (Magventure Inc.) will be used with the active coil facing away from the scalp, for sham stimulation. The coil is positioned under MRI guidance using real-time neuronavigation using Brainsight \[x,y,z= -38, 44, 26(left), +38, 44, 26 (right). To reproduce the nociceptive qualities of the stimulation, the B65-type stimulation coil - sham side - includes a built in electrical stimulator in the coil connector which "fires" a synchronous electrical pulse along with the TMS stimulus through electrodes mounted on the forehead or near the area of stimulation, to generate auditory and somatosensory (vibration) stimuli.
Active Bilateral Theta Burst Stimulation is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as rTMS for:
- Major Depressive Disorder
- Obsessive-Compulsive Disorder
🇪🇺 Approved in European Union as rTMS for:
- Major Depressive Disorder
🇨🇦 Approved in Canada as rTMS for:
- Major Depressive Disorder
- Obsessive-Compulsive Disorder
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Centre for Addiction and Mental HealthToronto, Canada
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Who Is Running the Clinical Trial?
Centre for Addiction and Mental HealthLead Sponsor
References
Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018]Current efforts to improve clinical effectiveness and utility of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression (MD) include theta burst stimulation (TBS), a patterned form of rTMS. Here, we investigated the efficacy of bilateral TBS to the dorsolateral prefrontal cortex (dlPFC) in patients with MD in additon to ongoing medication and psychotherapy.
Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. [2015]Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral-prefrontal cortex (DLPFC) exerts antidepressant effects. In this randomised controlled clinical trial we aimed to test the safety and therapeutic efficacy of bilateral theta-burst stimulation (TBS) as an add-on therapy to standard treatment of major depression.
The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. [2022]Suicide is a major health concern. Effective acute interventions are lacking. Recent studies have suggested an acute decrease of suicidal ideations following repetitive Transcranial Magnetic Stimulation (rTMS). However, placebo effects could not be excluded. We aimed to evaluate the acute effect of accelerated intermittent theta burst stimulation (TBS) on suicide risk in depression.
Non-inferiority of intermittent theta burst stimulation over the left V1 vs. classical target for depression: A randomized, double-blind trial. [2023]Repetitive transcranial magnetic stimulation (rTMS) targeting the visual cortex (VC) has shown antidepressant effects for major depressive disorder (MDD) in sham-controlled trials, but comparisons with rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) are lacking. We aimed to determine the non-inferiority of intermittent theta-burst stimulation (iTBS) over VC vs DLPFC for MDD.
Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. [2023]As a novel type of theta burst stimulation (TBS), continuous TBS (cTBS) has been shown to have mixed therapeutic effects for major depressive disorder (MDD) or bipolar depression (BD). Thus, we performed a meta-analysis of randomized controlled trials (RCTs) of cTBS for treating major depressive episodes in patients with MDD or BD.
A lack of efficacy of continuous theta burst stimulation over the left dorsolateral prefrontal cortex in autism: A double blind randomized sham-controlled trial. [2023]Although previous open-label trials suggest the therapeutic potential of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in autism spectrum disorder (ASD), methodological caveats exist. We conducted an 8-week randomized, double-blind sham-controlled trial to investigate the efficacy of inhibitory continuous theta burst stimulation (cTBS, a variant of rTMS) over the left DLPFC in individuals with ASD. Sixty children, adolescents and young adults (aged 8-30 years) with ASD without co-occurring intellectual disabilities were randomized to a 16-session 8-week cTBS versus sham stimulation course, with a follow-up 4 weeks after the trial. The Active group was not superior to the Sham group in any clinical or neuropsychological metrics at Week 8 or Week 12. Time effects of 8-week cTBS on symptoms and executive function were remarkable in both Active and Sham groups, with comparable response rates and effect sizes of changes in symptoms/cognition between groups. Our results from a sufficiently powered sample do not endorse the superior efficacy of cTBS over the left DLPFC to the shamed stimulation for children, adolescents and adults with ASD. These findings suggest that earlier positive open-label trial findings may be generalized by generalized/placebo effects. This highlights the urgent need for more rTMS/TBS studies with rigorous trial designs in ASD.
5-day multi-session intermittent theta burst stimulation over bilateral posterior superior temporal sulci in adults with autism-a pilot study. [2022]Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD.
Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]Intermittent theta burst stimulation (iTBS) using 600 pulses is an effective and FDA-cleared transcranial magnetic stimulation (TMS) protocol for major depressive disorder (MDD). Prolonged iTBS (piTBS) using 1,800 pulses could increase the effectiveness of TMS for MDD, but its real-world effectiveness is still debated. We assessed the safety, tolerability, and preliminary effectiveness of a 3x daily piTBS 1,800 pulses protocol delivered over 2 weeks in 27 participants. Only four participants (18.2%) achieved response, two of them achieving remission (9.1%). Five participants (18.5%) experienced tolerability issues. Future studies should focus on the neurophysiological effects of TBS protocols to determine optimal parameters.
Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study. [2022]Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression (MD). We retrospectively analyzed the efficacy of intermittent theta burst stimulation (iTBS) on the left dorsolateral prefrontal cortex (DLPFC) combined with low-frequency rTMS (LF-rTMS) on the right DLPFC as an additional therapy to standard medication treatment.