Trend-analysis reveals real and placebo rtms effects on addiction craving: a case-control observational study

Background and aims: Repetitive transcranial magnetic stimulation (rTMS) can be a potential therapeutic tool for the treatment of addiction, thanks to its ability to non-invasively modulate cortical excitability. In the present study, we investigated the short- and the long-term rTMS effects on craving behaviour and psychopathological symptoms in a sample of individuals suffering from gambling and cocaine use disorder. Methods: 42 individuals (age: 40.7 ± 9.5 years; 40 M) underwent an initial screening testing craving behaviour, by means of visual analogue scales, and psychopathological symptoms, by means of Symptom Checklist-90-R. Participants were subsequently assigned to a real or sham (placebo) rTMS treatment of 2 weeks delivered over the left dorso-lateral prefrontal cortex. To assess the short- and long-term effects of rTMS, participants were evaluated again after 1, 2, 4, 8, 12, 16, 20 and 24 weeks. Results: After an initial similar trend in the craving behaviour of the two groups, our trend analysis showed a long-lasting decrease (until 24 weeks) in the real-rTMS group, following a linear trend (p<0.001); whereas the sham-rTMS group progressively returned to the initial level after about 12 weeks, following a quadratic trend (p<0.001). In addition, we observed moderate-to-strong correlations (0.4<1) showing that placebo effects of rTMS were stronger in individuals showing higher level of psychopathological symptoms for the first 4 weeks. Conclusions: Our results supported a long-term rTMS efficacy for cocaine and gambling craving, for which evidence was still lacking, and the correlation of short-lasting placebo effects and psychopathological symptoms.