What is TMS and can it help treat withdrawal, addiction, and patients with SUDs like it can treat de

By Mark Gold, MD


In April, The Atlantic published a piece about a young woman who became a viral internet sensation after she was photographed wearing a futuristic-looking hat or device on her head.1 Some online commentators dubbed the large, grey headwear, connected by a strap under the chin, “the depression helmet.” What the commentators did not understand is that such devices are part of a safe, effective, FDA-approved treatment for depression: transcranial magnetic stimulation, or TMS. At the University of Florida, in 2008, I was part of a team that purchased one of the first TMS machines sold after FDA approval. We bought other machines and did TMS research as well. Since that time, the technique has been used successfully to treat depression around the world. It was also approved in 2013 for the treatment of pain associated with certain migraine headaches, and more recently approved for the treatment of Obsessive-Compulsive Disease.2


At least 100 randomized clinical trials have been completed in an attempt to find a MAT which might treat cocaine use disorder, employing over 50 chemical compound medications. With very little progress made from early work3, none have been shown to be particularly useful4, until the current day and TMS. Treatment must reverse more than acute or even chronic dopamine neuron effects of cocaine. The TMS research group at the National Institute of Drug Abuse (NIDA) in Baltimore works on TMS research, dopamine plasticity, cocaine and SUD-related dopamine changes. TMS offers us a chance to intervene against cocaine and other substance’s ability to change the firing rates and key brain circuits that ultimately reduce dopamine release. The TMS research group is working to define how SUDs change the brain, intrinsic and synaptic plasticity control dopamine neurons, and what might be done to return the brain to pre-drug functionality.5


NIDA TMS researchers were featured in a cover story on the science of addiction in National Geographic.6 This article describes how a psychiatrist in Italy, who has treated addiction for 30 years,  became interested in TMS and began using it for treatment. It also details the successful use of traditional TMS treatment on a chronic relapsing patient, treated as if he had a naturally occurring depression. The psychiatrist, patient, and NIDA researchers are all interviewed for the story. TMS is not shock therapy; it delivers electromagnetic pulses to the brain in dopamine rich areas, resulting in painless, rapid magnetic pulses delivered through a pad or cap or hat. It is called non-invasive, and clearly has the ability to use  magnetic stimulation to drive the brain’s circuitry with electric currents. TMS can increase and decrease cortical excitability, through high and low frequency wave generation.  Scientists are very excited about this as TMS may help rebuild neural connections, or possibly regenerate dopamine systems damaged by substance use. The psychiatrist featured in the National Geographic article, Luigi Gallimberti, MD, has subsequently used TMS to treat other addictions.


Medication assisted therapies are approved and used for detoxification, maintenance, and relapse prevention. Unfortunately, these do not address many of the changes produced by cocaine and other drugs. Even patients following these treatment plans and taking medications often feel a lack of energy, diminished pleasure, and declining enthusiasm, and drop out of treatment. TMS might not help people to stop using drugs, but it could be beneficial in helping with addiction and post-addiction related depression and anhedonia.7 TMS researchers have become part of a promising frontier for combating craving, addiction, relapse, and co-occurring depression. Greeting with laughter images of TMS devices, caps, and hats is a perfectly unhelpful reaction in the middle of a major opioid crisis.


FDA approval for treating depression through TMS piqued interest in applying the technique to substance use disorders, since depression is often a major part of SUDs, and a cause of relapses and overdoses, as a recent consensus review on the current state of non-invasive brain stimulation science pointed out. Neuroscience research has helped establish connections between substance-using behavior and particular neural circuits, which prompted additional interest in using TMS and related techniques to treat substance use disorders. TMS is no longer an experiment. With time, SUD researchers have compiled more studies on non-invasive brain stimulation, symptoms, and outcomes, leading to new reviews on relative effectiveness and future development prospects.

What did these studies find?


A recent review written by Zhang et al. found that excitatory repetitive TMS (rTMS) on the top left part of the brain—the dorsolateral prefrontal cortex—had a significant effect in decreasing substance consumption and cravings. Following this research, a consensus review found that it was actually hard to reach a consensus in the field because TMS done by one research group may not be the same as that done by others. Just putting TMS in the same place, or the correct one, has been a challenge until recent progress and FDA submissions8 allowed for consistency of application across different studies. The consensus review called for larger studies on non-invasive brain stimulation treatments for addiction, with “sham” controls as comparisons, and similar reporting practices. Zhang et al.’s review used meta-regressions, examining the frequency and intensity of pulses given in the treatment, the number of sessions, and the number of delivered pulses—all critically important parameters identified in the consensus review. And it provided a systematic study of different rTMS methods, which hasn’t been applied in previous studies.




Zhang et. al. reviewed the effects of TMS on reduced substance consumption and cravings for nicotine, alcohol, and illicit drugs. Patients were assessed for cravings through self-report questionnaires (or visual analog scales), and for consumption, they were assessed through self-reported substance intake, or the number of recurrence of use cases. The review was a meta-analysis of 26 randomized controlled trials from 2000-2018, involving 748 patients. Relative to sham stimulations, the review found that excitatory repetitive TMS on the left dorsolateral prefrontal cortex was associated with significant drops in substance consumption and cravings. Repetitive TMS simply refers to conventional TMS’s  consistent stimulation, applied over time to achieve more durable results. “Excitatory” TMS means that delivered pulses “excite” neuron activity in the selected brain area, as opposed to “inhibitory” TMS, which decreases activity.


The dorsolateral prefrontal cortex is part of the brain’s system for controlling what scientists classify as executive functioning, such as making choices and regulating impulses. It may be linked to substance use disorders, some researchers believe, because an imbalanced “hypoactive,” or inhibited system of executive function can increase desires like craving—limited self-control in the brain, in other words, can contribute to developing an addiction. The left dorsolateral prefrontal cortex may also be involved in motivation related to rewards. That means, the review asserts, that substance use would actually make the left side hyperactive, and Conventional TMS could target it to tamp down hyperactivity in addiction reward-seeking. The review found this to be the case in the studies it examined, though the results were somewhat limited because TMS for the left side mostly focused on illicit substances, whereas application to the right dorsolateral prefrontal cortex mostly focused on alcohol. The effects of TMS in the reviewed studies were also not that durable, and the review calls for finding ways to make the treatment more long-lasting.


Why is this important?


These reviews are important because they offer hope to patients and families combating substance use disorders, for whom any progress in the development of new treatments is a hopeful sign. Patients need the best help available, and TMS applications are much closer to being available for treatment than vaccines, which Research You Can Use previously pointed to as another promising avenue for treating addiction. TMS is safe and effective for depression. Depression, anhedonia, and suicidal thinking are commonly found in patients treated for SUDs with opioid agonists like methadone, buprenorphine, or suboxone, and TMS might also help here. Depression is often also found in post-addiction states. Patients in AA, NA, MAT or psychosocial post-addiction treatment programs often have depression, and these depressions do not seem as treatable by antidepressants as naturally occurring depressions. Depression can cause relapse, and it can persist, even during long-term abstinence, as described by Kitty Dukakis.9


SUDs are often accompanied by helplessness, despair, shame, and guilt, making a diagnosis of co-existing depression very important but, at times, difficult to offer. Rebuilding the brain’s pleasure system and restoring dopamine tone and connectivity are major neurobiological challenges for patients and physicians practicing addiction medicine. TMS may have such a direct healing effect, but only further studies will be able to prove it. To meet these major challenges, clinicians currently suggest, in addition to MATs and therapy, yoga, meditation, vigorous physical exercise, healthy eating, sleeping, 12 steps, and peer support. Many times, these are not enough. TMS offers considerable hope for those in need of another option, and NIDA and other addiction researchers around the world can make a big difference here. The consensus review authors remind us that one targeted brain application alone won’t remedy a given substance use disorder. Better research must establish the exact role of TMS in craving suppression, relapse prevention, well-being, and post-addiction mood and anxiety states. In the meantime, clinicians can actively look for patients with depression that existed before and after SUDs, diagnose them, and treat them. Treating both the SUD and the mood disorders will improve outcomes and help prepare for a new field of treatment options that combines behavioral management, pharmacotherapy, and brain stimulation, tailoring new methods to individual needs.




References:


  1. Hamblin, J. (April 19, 2019) The Helmet That ‘Resets’ Your Brain. The Atlantic

  2. FDA News Release. (August 17, 2018) FDA permits marketing of transcranial magnetic stimulation for treatment of obsessive compulsive disorder. Fda.gov

  3. Dackis, C.A., Gold, M.S.  (1985) New concepts in cocaine addiction: the dopamine depletion hypothesis. Neuroscience & Biobehavioral Reviews

  4. Czoty, P.W., Stoops, W.W., Rush, C.R. (2016) Evaluation of the “pipeline” for development of medications for cocaine use disorder: a review of translational preclinical, human laboratory, and clinical trial research. Pharmacological Reviews

  5. Francis, T.C. Gantz, S.C., Moussawi, K., Bonci, A. (2019) Synaptic and intrinsic plasticity in the ventral tegmental area after chronic cocaine. Current Opinion in Neurobiology

  6. Smith, F. (2017) How Science Is Unlocking the Secrets of Addiction. National Geographic

  7. Diana, M., Raij, T., Melis, M., Nummenmaa, A., Leggio, L., Bonci, A. (2017) Rehabilitating the addicted brain with transcranial magnetic stimulation. Nature Reviews Neuroscience

  8. Densford, F. (May 17, 2019) MagStim wins FDA nod, launches StimGuide TMS navigation system. Mass Device

  9. Seelye, K.Q. (December 31, 2016) Kitty Dukakis, a Beneficiary of Electroshock Therapy, Emerges as Its Evangelist. New York Times


Citations:


1. Ekhtiari, H., et al. (2019). Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead. Neuroscience and Biobehavioral Reviews


2. Zhang, J.J.Q., Fong, K.N.K., Ouyang, R., Siu, A.M.H., Kranz, G.S. (2019). Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. Addiction





Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.

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