rTMS for Depression and Substance Use Disorder
Recruiting in Palo Alto (17 mi)
Overseen byManish Jha, M.B.B.S
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Texas Southwestern Medical Center
Must not be taking: Alcohol, Benzodiazepines, Sedatives
Disqualifiers: Seizures, Brain lesions, Pregnancy, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This study is a small open-label feasibility trial of an accelerated course of repetitive transcranial magnetic stimulation (rTMS) for individuals with depression and stimulant use disorder \[including methamphetamine or cocaine use disorder (MUD/CUD)\].
Do I need to stop my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to understand any specific requirements.
What data supports the effectiveness of the treatment Accelerated Repetitive Transcranial Magnetic Stimulation (rTMS) for Depression and Substance Use Disorder?
Research shows that accelerated intermittent theta-burst stimulation (iTBS), a form of rTMS, can reduce cocaine use and cravings, and is well-tolerated. Additionally, iTBS has been found to be effective in treating depression, suggesting it may help with both depression and substance use disorders.
12345Is rTMS safe for treating depression and substance use disorder?
Research shows that rTMS, including its variations like iTBS, is generally safe for treating depression, with mild headaches being the most common side effect. Studies have found it to be well-tolerated, with similar safety profiles to other forms of rTMS.
678910How is the treatment rTMS for depression and substance use disorder different from other treatments?
The treatment rTMS (repetitive transcranial magnetic stimulation) is unique because it uses magnetic fields to stimulate specific areas of the brain, such as the prefrontal cortex, which can help modulate brain circuits involved in depression and addiction. Unlike traditional treatments, it is non-invasive and can be administered in accelerated sessions, potentially offering quicker relief with fewer side effects.
125711Eligibility Criteria
This trial is for individuals who are struggling with both depression and stimulant use disorder, which includes problems with drugs like methamphetamine or cocaine. Participants should be suitable candidates for the rTMS treatment.Inclusion Criteria
I am between 18 and 65 years old.
Have a PHQ9 of greater than or equal to five (5)
Be able to sufficiently understand, speak, and read English to provide informed consent and ask relevant questions, and be willing to comply with all study procedure instructions
+4 more
Exclusion Criteria
I have a documented history of brain lesions or tumors.
Current pregnancy as determined by a urine screening
Current or lifetime manic or hypomanic episode, defined by MINI diagnostic interview
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive an accelerated course of repetitive Transcranial Magnetic Stimulation (rTMS) with up to four sessions per day, five days a week, for a total of 50 sessions over three weeks
3 weeks
Daily visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments of craving, substance use, and mood symptoms
1 week
1 visit (in-person)
Participant Groups
The study is testing an accelerated course of repetitive transcranial magnetic stimulation (rTMS), a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain, on people with depression and stimulant abuse issues.
1Treatment groups
Experimental Treatment
Group I: rTMS InterventionExperimental Treatment1 Intervention
Eligible participants who are enrolled will receive an accelerated course of repetitive Transcranial Magnetic Stimulation.
Accelerated Repetitive Transcranial Magnetic Stimulation is already approved in United States, European Union, Canada for the following indications:
πΊπΈ Approved in United States as rTMS for:
- Major Depressive Disorder
- Obsessive Compulsive Disorder
- Smoking cessation
πͺπΊ Approved in European Union as rTMS for:
- Major Depressive Disorder
- Obsessive Compulsive Disorder
π¨π¦ 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:
UT Southwestern Medical CenterDallas, TX
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Who Is Running the Clinical Trial?
University of Texas Southwestern Medical CenterLead Sponsor
References
Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study. [2020]There are no effective treatments for cocaine use disorder (CUD), a chronic, relapsing brain disease characterized by dysregulated circuits related to cue reactivity, reward processing, response inhibition, and executive control. Transcranial magnetic stimulation (TMS) has the potential to modulate circuits and networks implicated in neuropsychiatric disorders, including addiction. Although acute applications of TMS have reduced craving in urine-negative cocaine users, the tolerability and safety of administering accelerated TMS to cocaine-positive individuals is unknown. As such, we performed a proof-of-concept study employing an intermittent theta-burst stimulation (iTBS) protocol in an actively cocaine-using sample. Although our main goal was to assess the tolerability and safety of administering three iTBS sessions daily, we also hypothesized that iTBS would reduce cocaine use in this non-treatment seeking cohort. We recruited 19 individuals with CUD to receive three open-label iTBS sessions per day, with approximately a 60-min interval between sessions, for 10 days over a 2-week period (30 total iTBS sessions). iTBS was delivered to left dorsolateral prefrontal cortex (dlPFC) with neuronavigation guidance. Compliance and safety were assessed throughout the trial. Cocaine use behavior was assessed before, during, and after the intervention and at 1- and 4-week follow-up visits. Of the 335 iTBS sessions applied, 73% were performed on participants with cocaine-positive urine tests. Nine of the 14 participants who initiated treatment received at least 26 of 30 iTBS sessions and returned for the 4-week follow-up visit. These individuals reduced their weekly cocaine consumption by 78% in amount of dollars spent and 70% in days of use relative to pre-iTBS cocaine use patterns. Similarly, individuals reduced their weekly consumption of nicotine, alcohol, and THC, suggesting iTBS modulated a common circuit across drugs of abuse. iTBS was well-tolerated, despite the expected occasional headaches. A single participant developed a transient neurological event of uncertain etiology on iTBS day 9 and cocaine-induced psychosis 2 weeks after discontinuation. It thus appears that accelerated iTBS to left dlPFC administered in active, chronic cocaine users is both feasible and tolerable in actively using cocaine participants with preliminary indications of efficacy in reducing both the amount and frequency of cocaine (and other off target drug) use. The neural underpinnings of these behavioral changes could help in the future development of effective treatment of CUD.
Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Cocaine Use Disorder: A Pilot Study. [2020]Transcranial Magnetic Stimulation (TMS) is earning a role in the therapeutic arsenal of cocaine use disorder (CUD). A widespread and still growing number of studies have reported beneficial use of repeated TMS (rTMS) in reduction of craving, intake and cue-induced craving in cocaine addicts. In spite of these encouraging findings, many issues are still unresolved such as brain area to be stimulated, laterality of the effects, coil geometry and stimulation protocols/parameters. Intermittent theta burst stimulation (iTBS) is a more tolerable protocol administered at lower intensities and shorter intervals than conventional rTMS protocols. Yet, its effects on cocaine craving and length of abstinence in comparison with standard high frequency (10-15 Hz) protocols have never been evaluated so far. In the present paper, we describe the effect of the bilateral iTBS of the prefrontal cortex (PFC) in a population (n = 25) of treatment-seeking cocaine addicts, in an outpatient setting, and compare them with 15 Hz stimulation of the same brain area (n = 22). The results indicate that iTBS produces effects on cocaine consumption and cocaine craving virtually superimposable to the 15 Hz rTMS group. Both treatments had low numbers of dropouts and similar side-effects, safety and tolerability profiles. While larger studies are warranted to confirm these observations, iTBS appears to be a valid approach to be considered in treatment-seeking cocaine addicts, especially in light of its brief duration (3 min) vs. 15 Hz stimulation (15 min). The use of iTBS would allow increasing the number of patients treated per day with current rTMS devices, thus reducing patient discomfort and hopefully reducing drop-out rates without compromising clinical effectiveness.
Accelerated rTMS: A Potential Treatment to Alleviate Refractory Depression. [2020]Three decades of clinical research on repetitive transcranial magnetic stimulation (rTMS) has yielded one clear treatment indication in psychiatry for major depression disorder (MDD). Although the clinical response equals the standard treatment algorithms, the effect sizes on the beneficial outcome remain rather modest. Over the last couple of years, to improve the efficacy in resistant depression, two new avenues have been developed: personalization and intensifying rTMS treatment. For the latter, we retrospectively compared accelerated high-frequency rTMS (arTMS) with accelerated intermittent theta burst stimulation (aiTBS) in the refractory depressed state. Although the clinical efficacy was not significantly different between both protocols, our observations substantiate the potential of the accelerated stimulation to shorten the treatment duration from the depressed state to the response state. Any time gain from the depressed state to the recovered state is in the patients' interest.
The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. [2023]Intermittent theta burst stimulation (iTBS) when applied over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be equally effective and safe to treat depression compared to traditional repetitive transcranial magnetic stimulation (rTMS) paradigms. This protocol describes a funded single-centre, double-blind, randomized placebo-controlled, clinical trial to investigate the antidepressive effects of iTBS and factors associated with an antidepressive response.
Accelerated iTBS changes perfusion patterns in medication resistant depression. [2022]Accelerated intermittent Theta Burst Stimulation (aiTBS) is a new non-invasive brain stimulation protocol developed to rapidly treat medication resistant depression (MRD). However, to examine potential neurobiological changes only few sham-controlled studies combining pre/post treatment measures and brain imaging data are available. Consequently, with this Arterial Spin Labeling (ASL) brain imaging study, we investigated in 45 antidepressant-free MRD patients whether clinical improvement following aiTBS treatment applied to the left dorsolateral prefrontal cortex (Trial registration: http://clinicaltrials.gov/show/NCT01832805) would be associated with specific changes in brain perfusion patterns. We primarily expected frontolimbic perfusion changes following active and not sham aiTBS. Our ASL brain imaging findings showed that active aiTBS resulted in prompt perfusion increases in functionally connected brain regions such as the ventromedial prefrontal cortex and the right inferior parietal lobule. We also observed decreased perfusion in the left parahippocampal gyrus and the right posterior cerebellar lobe after active aiTBS. On the other hand, sham aiTBS resulted in right angular perfusion decreases, an area known to be involved in placebo responses. Overall, our perfusion findings indicate that active aiTBS treatment promptly affects brain regions functionally and structurally connected to the stimulated area and known to be part of deregulated brain circuits when clinically depressed. Placebo responses may be part of the clinical effects of accelerated ITS protocols. Our current results further shed light on how accelerated rTMS treatment protocols may promptly improve depressive symptoms in MRD.
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.
Accelerated theta-burst repetitive transcranial magnetic stimulation for depression in South Africa. [2020]This case series documents local experience using accelerated theta-burst repetitive transcranial magnetic stimulation (rTMS) as a supplementary treatment for depression in both major depressive disorder (MDD) and bipolar disorder (BD). Nine consenting patients (MDD = 7; BD = 2) each received 20 accelerated theta-burst sessions over 8 days. Improvement was monitored using the Centre for Epidemiological Studies Depression (CES-D) Scale and the Clinical Global Impression (CGI) Scale at baseline, at day 5 and at day 8 of rTMS treatment. We performed a Wilcoxon matched-pairs signed-rank test to determine whether there was a difference in scores from baseline to post-treatment. The CES-D scores decreased significantly from baseline to post-treatment (Z = -2.547, p = 0.011) with five patients experiencing at least a 50% symptom reduction on the CES-D. CGI severity scores also decreased significantly between baseline and post-treatment (Z = -2.547, p = 0.011). The most commonly reported adverse effect was mild headaches, lasting a few hours during and after rTMS treatment. The findings suggest that the accelerated theta-burst rTMS protocol for depression is well tolerated with most patients also experiencing symptomatic improvement by day 8.
Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. [2022]Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37Β·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression.
Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for major depressive disorder: A systematic review and meta-analysis. [2023]Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)/bilateral-rTMS (Bi-rTMS) had similar efficacy, acceptability, and safety profiles for antidepressant treatment-resistant major depressive disorder (AD-TRD). In our sensitivity analysis that excluded a study that compared Bi-TBS with Bi-rTMS for older adults, all efficacy outcomes were also comparable between iTBS and HF-rTMS. Because iTBS does not require higher stimulation intensity and a longer stimulus time than conventional HF-rTMS protocols, we speculated that for those with AD-TRD, iTBS/Bi-TBS is a more helpful therapeutic modality in clinical practice than HF-rTMS/Bi-rTMS.
Task-Modulated Brain Activity Predicts Antidepressant Responses of Prefrontal Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Control Study. [2022]Prolonged intermittent theta-burst stimulation (piTBS) and repetitive transcranial magnetic stimulation (rTMS) are effective antidepressant interventions for major depressive disorder (MDD). Cognition-modulated frontal theta (frontalΞΈ) activity had been identified to predict the antidepressant response to 10-Hz left prefrontal rTMS. However, whether this marker also predicts that of piTBS needs further investigation.