Effects of Non-invasive Brain Stimulation on Stimulant Craving in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-Analysis

Tianye Ma, Yurong Sun, Yixuan Ku, Tianye Ma, Yurong Sun, Yixuan Ku

Abstract

Dopamine system plays a pivotal role in specific kinds of substance use disorders (SUD, i. e., cocaine and methamphetamine use disorders). Many studies addressed whether dopamine-involved craving could be alleviated by non-invasive brain stimulation (NIBS) techniques. Nevertheless, the outcomes were highly inconsistent and the stimulating parameters were highly variable. In the current study, we ran a meta-analysis to identify an overall effect size of NIBS and try to find stimulating parameters of special note. We primarily find 2,530 unduplicated studies in PubMed, Psychology and Behavioral Sciences Collection, PsycARTICLES, PsycINFO, and Google Scholar database involving "Cocaine"/"Amphetamine"/"Methamphetamine" binded with "TMS"/"tDCS"/"non-invasive stimulation" in either field. After visual screening, 26 studies remained. While 16 studies were further excluded due to the lack of data, invalid craving scoring or the absence of sham condition. At last, 16 units of analysis in 12 eligible studies were coded and forwarded to a random-effect analysis. The results showed a large positive main effect of stimulation (Hedge's g = 1.116, CI = [0.597, 1.634]). Further subgroup analysis found that only high-frequency repetitive transcranial magnetic stimulation (rTMS) could elicit a significant decrease in craving, while the outcome of low-frequency stimulation was relatively controversial. Moreover, univariate meta regression revealed that the number of pulses per session could impose negative moderation toward the intervention. No significant moderation effect was found in types of abuse, overall days of stimulation and other variables of stimulating protocol. In conclusion, this meta-analysis offered a persuasive evidence for the feasibility of using NIBS to remit substance addictive behavior directly based on dopamine system. We also give clear methodological guidance that researchers are expected to use high-frequency, sufficiently segmented rTMS to improve the efficacy in future treatments.

Keywords: addiction; craving; dopamine system; non-invasive brain stimulation; substance use disorders.

Copyright © 2019 Ma, Sun and Ku.

Figures

Figure 1
Figure 1
Dopamine reward system involved in the therapeutic effect of NIBS. In the illustrated pathway, dopaminergic neurons in ventral tegmental area (VTA) projects the reward signal to medium spiny neurons (MSNs) in ventral striatum by which the cortico-striatal connection is modulated. While prefrontal regions (pyramidal neurons) including dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC) give feedback to these regions (Gorelova and Yang, ; Frankle et al., 2006). With non-invasive brain stimulation alters activation in prefrontal regions, the VTA reactivity will be enhanced which results in the recovery of DA increase in the downstream areas. The regions with a transparent circle rearward are not on the cortical surface.
Figure 2
Figure 2
Flow diagram of the study selection procedure.
Figure 3
Figure 3
Forest plot of the estimated effect sizes. Authors and years of publication of each unit of analysis are shown in the very left column. The words in the brackets indicate the information of within-study subgroups (HF, high frequency; LF, low frequency; LDLPFC, left dorsolateral prefrontal cortex; RDLPFC, right dorsolateral prefrontal cortex). In the forest plot, the length of each bar illustrates the confidence interval of the corresponding unit. The size of each empty circle illustrates the relative weight of each unit which is also showed by the black bars on the right-hand side.
Figure 4
Figure 4
The therapeutic outcome is modulated by the number of pulses per session. For clarity, the overlapped values of regressor were randomly jittered. The solid line is the fixed-effect regressive function for the regressor. The size of each bubble represents the study's relative weight which was calculated as the inverse of the variance. Error bars indicate the 95% CIs. The markers abut to the bubbles correspond to the index of studies in the Appendix.

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