SAN FRANCISCO – Transcranial magnetic stimulation shows considerable promise as a treatment for the core symptom domains and associated features of autism spectrum disorder, but its true potential has yet to be defined, Eric Hollander, MD, said at the annual conference of the Anxiety and Depression Association of America.

“It’s a promising tool. There’s a lot of hope. There have been a range of scattered studies. But there is still a lot more work that needs to be done in terms of defining the optimal target structures in the brain, the dose and frequency of treatment, and which symptoms respond best,” said Dr. Hollander, director of the autism and obsessive-compulsive spectrum program as well as the anxiety and depression program at Albert Einstein College of Medicine in New York.

He pointed to a 2016 white paper by experts in the field entitled, “Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and a road map for future research.”

The authors characterized transcranial magnetic stimulation (TMS) for autism spectrum disorder (ASD) as “a novel, possibly transformative approach” but added a strong cautionary note.

“The available literature on the TMS use in ASD is preliminary, composed of studies with methodological limitations. Thus, off-label clinical rTMS [repetitive TMS] use for therapeutic interventions in ASD without an investigational device exemption and outside of an IRB [institutional review board]-approved research trial is premature pending further, adequately powered and controlled trials,” according to the white paper by the TMS in ASD Consensus Group (Autism Res. 2016 Feb;9[2]:184-203).

ASD support groups are eager to see TMS developed as a treatment, Dr. Hollander said. This is largely a result of the 2016 publication of a nonfiction book entitled, “Switched On: A Memoir of Brain Change and Emotional Awakening” (New York: Spiegel & Grau, 2016). Author John Elder Robison is a high-functioning individual with ASD who describes his dramatic improvement in response to TMS therapy in an early clinical trial conducted at Boston’s Beth Israel Deaconess Medical Center.

Dr. Hollander has been extensively involved in pioneering studies of TMS for the treatment of depression – currently its only Food and Drug Administration–approved indication – as well as for obsessive-compulsive disorder. His recent work on TMS for the treatment of ASD has focused on the noninvasive therapy’s ability to favorably affect the excitatory/inhibitory imbalance that characterizes ASD. This imbalance is tied chiefly to abnormal glutamatergic and gamma-aminobutyric acid–ergic neurotransmission in the neocortex, cerebellum, hippocampus, and amygdala. The imbalance is thought to be responsible for the cognitive, sensory, learning, memory, and motor deficits, as well as increased propensity for seizures, associated with ASD.

This excitatory/inhibitory imbalance is marked by increased cortical excitability and decreased inhibition within the densely packed cortical minicolumns of neurons, which are organized into pathways and circuits.

“You can use TMS as a treatment, or you can use it as a research probe to look at these mechanisms by turning on or off pathways,” the psychiatrist explained. “These densely packed minicolumns are like wires with poor insulation, which results in impairment in the ability to distinguish a stimulus from background noise. In the pathologic condition, you’re getting a rapid firing which doesn’t really differentiate what’s a true signal from what’s background noise.”

Therapeutically, TMS can be employed to improve that signal-to-noise ratio, either by reducing excitation or increasing inhibition. Potential TMS targets in autism include the anterior cingulate cortex, the supplementary or presupplementary motor area, the dorsal medial prefrontal cortex, the dorsal lateral prefrontal cortex, and the cerebellum. More than a dozen published TMS studies – albeit open-label, uncontrolled, and featuring only handfuls of patients – have demonstrated long-lasting improvements in the two core symptom domains of ASD: reduced repetitive behaviors and improved social relatedness and interpersonal functioning, Dr. Hollander said.

A wide range of associated noncore symptoms, including disruptive behaviors such as self-injury or aggression, impulse control, social anxiety, and depression, also might be targeted.

“In our clinical practice, we tend to treat adults with ASD who have a lot of OCD [obsessive-compulsive disorder] and repetitive behavior symptoms but also mood or anxiety symptoms or PTSD [posttraumatic stress disorder] symptoms as a result of earlier bullying. You can adapt your treatment to the target symptoms, so if there’s a lot of OCD-type symptoms, you might use low-frequency TMS at 1 Hz to target the supplementary motor area. If people are coming in with depressive symptoms, you can use the dorsolateral prefrontal cortex depression target. If they have a lot of anxiety, you can target the right frontal anxiety loop with low-frequency TMS. Or with a lot of PTSD symptoms, you can use high-frequency stimulation of the dorsolateral prefrontal cortex at 20 Hz,” Dr. Hollander said.

An important caveat, however, is that ASD is associated with an increased risk of seizures and other EEG abnormalities, so low-frequency TMS generally is preferable because of its greater safety.

Another challenge is administering TMS in children.

“Kids move around a lot, so you’re probably going to be using briefer stimulation parameters like theta burst stimulation rather than longer treatment parameters,” Dr. Hollander said.

That being said, there are more than two dozen published studies of TMS for treatment of children and adolescents, and surveys indicate that these patients generally find it quite tolerable. Dr. Hollander noted that in one study, children and adolescents ranked it somewhere between watching television and a long car ride. This placed TMS on the midrange of a tolerability scale: not as good as having a birthday party or playing a game, but better than going to the dentist, throwing up, or, in last place, getting a shot. Of the 39 youngsters, 34 indicated that they would recommend TMS to a friend.

Dr. Hollander reported receiving research funding from the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke. He serves as a consultant to roughly half a dozen pharmaceutical companies.

bjancin@frontlinemedcom.com

Transcranial magnetic stimulation shows promise in autism spectrum disorder