Abstract
ObjectivesTranscranial magnetic stimulation (TMS) holds potential promise as a therapeutic modality for disorders of addiction. Our previous findings indicate that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsal–lateral prefrontal cortex (DLPFC) and low-frequency rTMS over the right DLPFC can reduce drug craving for methamphetamine. One major issue with rTMS is the duration of treatment and hence potential dropout rate. Theta burst stimulation (TBS) has been recently shown to be non-inferior relative to repetitive transcranial magnetic stimulation for major depression. Here, we aim to compare the clinical efficacy and tolerability of intermittent and continuous theta burst stimulation protocols targeting left or right dorsolateral prefrontal cortex on methamphetamine craving in abstinent-dependent subjects.MethodsIn this randomized single-blind pilot study, 83 abstinent methamphetamine-dependent subjects from a long-term residential treatment program were randomly allocated into three groups: intermittent theta burst stimulation (iTBS) over the left DLPFC (active group), continuous theta burst stimulation (cTBS) over the left DLPFC (active control group), or cTBS over the right DLPFC (active group) was administered twice daily over 5 days for a total of 10 sessions. We measured the primary outcome of cue-induced craving and secondarily sleep quality, depression, anxiety, impulsivity scores, and adverse effects.ResultsWe show a pre- vs. postintervention effect on craving, which, on paired t tests, showed that the effect was driven by iTBS of the left DLPFC and cTBS of the right DLPFC, reducing cue-induced craving but not cTBS of the left DLPFC. We did not show the critical group-by-time interaction. The secondary outcomes of depression, anxiety, and sleep were unrelated to the improvement in craving in the left iTBS and right cTBS group. In the first two sessions, self-reported adverse effects were higher with left iTBS when compared to right cTBS. The distribution of craving change suggested greater clinical response (50% improvement) with right cTBS and a bimodal pattern of effect with left iTBS, suggesting high interindividual variable response in the latter.ConclusionAccelerated twice-daily TBS appears feasible and tolerable at modulating craving and mood changes in abstinent methamphetamine dependence critically while reducing session length. We emphasize the need for a larger randomized controlled trial study with a sham control to confirm these findings and longer duration of clinically relevant follow-up.Clinical Trial RegistrationChinese Clinical Trial Registry number, 17013610.
Highlights
Disorders of addiction, or compulsive drug-seeking behaviors despite adverse negative consequences, are characterized by abnormal brain network function (Goldstein and Volkow, 2011; Everitt and Robbins, 2016)
There were no significant differences in demographic variables between study completers and non-completers
There were no group differences at baseline in age, years of drug abuse history, number of cigarettes smoked per day, monthly dosage, interval between admission into the rehabilitation center and entry into the study, baseline craving, sleep quality, depression, anxiety, and impulsivity (Table 1)
Summary
Compulsive drug-seeking behaviors despite adverse negative consequences, are characterized by abnormal brain network function (Goldstein and Volkow, 2011; Everitt and Robbins, 2016). High-frequency excitatory rTMS of the left DLPFC has been reported to be effective in cocaine use disorder [e.g., 15 Hz/8 sessions/100% motor threshold (Terraneo et al, 2016), 15 Hz/10 sessions/100% motor threshold (Politi et al, 2008), and 10 Hz/single session/90% motor threshold (Camprodon et al, 2007)] and nicotine use disorder [e.g., high frequency/13 session/120% motor threshold, deep TMS over bilateral lateral prefrontal and insula (Dinur-Klein et al, 2014), 10 Hz/10 sessions/100% motor threshold, and 20 Hz/8 sessions/110% over the DLPFC (Amiaz et al, 2009; Sheffer et al, 2018)] Other stimulants such as methamphetamine craving decreased with high-frequency left DLPFC rTMS (10 Hz/5 sessions/80% motor threshold) (Su et al, 2017), but with enhanced cue craving observed with low frequency (1 Hz/single session/100% motor threshold) (Li et al, 2013b). Alcohol-dependent subjects showed a different response as a function of laterality with decreased craving with highfrequency rTMS of the right DLPFC (10 Hz/10 sessions/110% motor threshold) (Mishra et al, 2010), with no effects on craving in female alcoholics with high-frequency rTMS of the left DLPFC (20 Hz/10 sessions/110% motor threshold) (Höppner et al, 2011)
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