Neuromodulation for Nicotine Use in Schizophrenia


What neuromodulation can be used to specifically target nicotine users with schizophrenia? This research may tell us.




“I have sought to identify specific circuits for nicotine dependence that I can then leverage into schizophrenia-specific treatment for smoking cessation,” said Heather Ward, MD, a psychiatrist at Vanderbilt University Medical Center, in her American College of Neuropsychopharmacology 2023 Annual Meeting session as part of the panel, “Hit Me With Your Best Shot: Personalized Targeting of Neuromodulation for Substance Use Disorders.”

Nicotine dependence is the top preventable cause of early mortality in schizophrenia, with a 20-year decrease in life expectancy due to associated medical consequences such as heart disease, stroke, lung cancer, and more. Additionally, the prevalence of tobacco use in those with schizophrenia is 3 times of that of the general population. Compounding this problem are the varied versions of nicotine now available, including vaping, lozenges, patches, as well as cigarettes. Despite these facts, tobacco treatments are significantly less effective in patients with schizophrenia.

To begin, Ward sought to define which circuit of the brain should be targeted. She and fellow investigators found it in the default mode network (DMN). She then endeavored to engage said circuit using 1 pharmacologic intervention and 1 neuromodulatory intervention, constructing a model that shows decreasing craving decreases DMN connectivity in schizophrenia, and vice versa.

Ward’s exciting preliminary data indicates that neuromodulation, specifically inhibitory DMN-targeted cTBS, could be effective as a schizophrenia-specific intervention for nicotine use. With multiple sessions—5 consecutive days, assessed via scan 2 to 7 days before treatment and 2 to 7 days following treatment—patients with schizophrenia (n=7) indicated they had fewer cravings for nicotine post-neuromodulation session. Furthermore, participants in the non-psychosis group (n=14) did not indicate a change in craving, suggesting this treatment exclusively targets those with schizophrenia.

“Some people would suggest that we have actually just identified the area for an agent with pharmacotherapy, that maybe we could be developing small molecules that can modulate DMN connectivity,” said Ward. “But I want to develop TMS for smoking cessation. I think it is fabulous that we have evidence that multiple sessions of cTBS can reduce craving.”

The research also indicates different types of modulation could have alternative effects. Ward noted that iTBS had an excitatory effect, actually increasing craving for nicotine. “Maybe it is easier to increase craving than it is to decrease craving,” Ward commented.

Ultimately, Ward’s hope is that TMS could be used to help patients achieve a nicotine-free status. “It is exciting because we are one step closer towards improving smoking cessation treatment in patients with schizophrenia,“ said Ward. “I think it is clear we will need more sessions for that.”

While the literature is limited, other research, like that from Corripio et al, has sought to understand the effectiveness of neuromodulation—in this case, deep brain stimulation—in treatment-resistant schizophrenia.1 Overall, this seems like an understudied, but viable future option for those with schizophrenia.

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1. Corripio I, Roldán A, McKenna P, et al. Target selection for deep brain stimulation in treatment resistant schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2022;112:110436.

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