Noninvasive Brain Stimulation Helps Treat Cocaine Addiction

Liam Davenport

December 14, 2015

Early results suggest that repetitive transcranial magnetic brain stimulation (rTMS) reduces both substance use and cravings in cocaine addicts, offering hope of a novel medical treatment for patients with this addiction.

The researchers found that rTMS to the dorsolateral prefrontal cortex (PFC) significantly improved outcomes in this patient population compared with standard pharmaceutical therapy, even among individuals who later switched to brain stimulation.

Although recognizing the preliminary nature of the findings, Antonello Bonci, MD, scientific director, National Institute on Drug Abuse (NIDA), and adjunct professor, John Hopkins University, Baltimore, Maryland, told Medscape Medical News that "this could be the medical treatment that can really make patients make that big jump in terms of quality of life, in terms of reduction in cravings."

The research was published online December 4 in European Neuropsychopharmacology.

Cuts Cravings

The team recruited 32 cocaine-addicted patients who were seeking treatment for their addiction at the teaching hospital affiliated with the University of Padua. The participants were randomly assigned to an rTMS protocol or to standard pharmacologic agents to treat the symptoms associated with cocaine addiction for 29 days.

rTMS consisted of one session per day for 5 days, followed by one session per week for 3 weeks. This was followed by a 63-day follow-up period in which all participants were offered rTMS therapy.

All 16 patients in the rTMS group and 13 (81%) of those in the control group, which received standard therapy, completed stage one of the study.

Participants who received rTMS had a significantly higher number of cocaine-free urine drug test results than those in the control group (P = .004), with 69% and 19%, respectively, having positive outcomes, defined as either remaining cocaine free or remaining in the study.

Multivariate logistic regression analysis that controlled for age indicated that rTMS had a significant effect on outcomes (odds ratio of a positive outcome, of 6.47; P = .035).

Among the 10 patients who switched to rTMS during stage two of the study, three had a positive result on drug screening, compared with eight during stage one, representing a significant reduction (P = .037).

rTMS also significantly reduced craving scores in comparison with control therapy in stage one of the study (P = .038), although this effect did not persist into the second stage (P > .05). Both rTMS and control therapy improved depressive symptoms, with no significant difference between the treatments.

Potential Mechanism

Dr Bonci explained that there are two theories as to how rTMS reduces cravings and substance use among cocaine addicts. One is that the stimulation causes activation of the dorsolateral PFC.

He noted that previous studies have shown that the dorsolateral PFC is at the center of a wide network of areas in the frontal, temporal, and limbic brain regions. Moreover, in some of these areas, exposure to cocaine produces hypofunctional alterations and diffused responses. One theory as to why this occurs is that the rTMS is causing a downstream stimulation of this network.

"The other theory is that it is not really a pure activation, as we think, but that it's a scrambling signal," Dr Bonci said.

"You imagine that cocaine has created a very cemented circuitry that works in a certain pattern of activity, and now you insert an extraneous and external electromagnetic signal that scrambles the wavelength, the activity, of these brain regions.

"You interfere with the routine pattern of activity that cocaine produces in these brains. Again, these are only theories, as far as I can say for now," he added.

Although Dr Bonci envisages rTMS being used on its own in cocaine addicts, "we know that nothing is done in isolation. These patients, the vast majority of them, will need medications for a variety of pre-existing conditions," he said.

"These patients will benefit and are benefitting from psychological support therapy, so [rTMS will be used] most likely in combination with other interventions."

Dr Bonci also pointed out that rTMS is already used clinically for depression and is being tested in several centers in the United States and Europe for smoking cessation and alcohol use disorders and as a cognitive enhancer in patients with forms of dementia.

Ruling Out a Placebo Effect

To validate the current findings, Dr Bonci and colleagues are planning a placebo-controlled study involving a sham rTMS stimulator. This study will include hundreds of participants and will be conducted in conjunction with several centers, including Northwestern University, in Chicago, and NIDA.

"That's very important, because we need to rule out any possibility of a placebo effect, because it's very likely, at least in the very early stages, there could be a placebo effect," Dr Bonci noted.

Sham rTMS could not be used in the current study, Dr Bonci explained, because the researchers first needed to validate the procedure so as to provide "a stronger rationale" for further assessment.

Furthermore, the investigation was conducted in a clinic, and the patients did not want to have a placebo. "These were extremely highly motivated treatment seekers, so we had to offer rTMS, the real thing, even if it's at the experimental stage," Dr Bonci said.

One question that they hope to answer with further study concerns how long the effect of rTMS lasts. Dr Bonci noted that in their clinic in Padua, several of the patients received the treatment more than a year ago, and so its effects can last, in some patients, at least that long.

"There must be some form of plasticity that happens as a consequence of rTMS. But not all patients will be equal, and I'm predicting that some patients are going to be fine after the treatment protocol of 4 weeks of stimulation. Some patients will come back once a week, maybe, some patients will come back after a month, and so on," he said.

Andreas Meyer-Lindenberg, MD, PhD, director of the Central Institute of Mental Health Mannheim, in Germany, and editor of European Neuropsychopharmacology, said the study "represents a creative approach to a disorder that is notoriously difficult to treat in the real world.

"These pilot data also show that biological treatments nowadays reach far beyond medications and that new neuroscience methods may be used for targeted changes in brain regions relevant for complex mental disorders," Dr Meyer-Lindenberg added.

The authors were variously funded by IRCCS San Camillo, Venice, Italy; the Novella Fronda Foundation; the Department of Neuroscience, University of Padua; the NIDA Intramural Research Program; the Division of Intramural Clinical and Biological Research; and the National Institute on Alcohol Abuse and Alcoholism. Dr Meyer-Lindenberg reports no relevant financial relationships.

Eur Neuropsychopharmacol. Published online December 4, 2015. Full text


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