Multiple Sessions of Transcranial Direct Current Stimulation (tDCS) Reduced Craving and Relapses for Alcohol Use: A Randomized Placebo-Controlled Trial in Alcohol Use Disorder

Jaisa Klauss, Quézia S Anders, Luna V Felippe, Michael A Nitsche, Ester M Nakamura-Palacios, Jaisa Klauss, Quézia S Anders, Luna V Felippe, Michael A Nitsche, Ester M Nakamura-Palacios

Abstract

Background: Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, has been studied as an adjunctive therapeutic agent for alcohol dependence. In a previous study, we showed that five consecutive sessions of tDCS applied bilaterally over the dorsolateral prefrontal cortex (dlPFC) reduced relapse to the use of alcohol in alcohol use disorder (AUD) outpatients. However, no changes on craving scores were observed. In the present study, we investigated if an extended number of sessions of the same intervention would reduce craving and relapses for alcohol use in AUD inpatients. Methods: Thus, a randomized, double-blind, sham-controlled, clinical trial with parallel arms was conducted (https://ichgcp.net/clinical-trials-registry/NCT02091284). AUD patients from two private and one public clinics for treatment of drug dependence were randomly allocated to two groups: real tDCS (5 × 7 cm2, 2 mA, for 20 min, cathodal over the left dlPFC, and anodal over the right dlPFC) and sham-tDCS. Real or sham-tDCS was applied once a day, every other day, in a total of 10 sessions. Craving was monitored by a 5-item obsessive compulsive drinking scale once a week (one time before, three times during and once after brain stimulation) over about 5 weeks. Results: Craving scores progressively decreased over five measurements in both groups but were significantly reduced only in the real tDCS group after treatment. Corrected Hedges' within-group (initial and final) effect sizes of craving scores were of 0.3 for the sham-tDCS and of 1.1 for the real tDCS group. Effect size was 3-fold larger in the real tDCS group. In addition, the between-group analysis on craving score difference was nearly significant, and the effect size was 0.58, in favor for a larger effect in the real tDCS group when compared to sham-tDCS. Furthermore, in a 3-months follow-up after intervention, 72.2% of sham-tDCS group relapsed to the alcohol use whereas 72.7% of tDCS group were abstinent. Conclusions: Multiple sessions of bilateral prefrontal tDCS were well tolerated with no significant adverse events. Thus, extended repetitive bilateral tDCS over the dlPFC is a promising adjunctive clinical tool that could be used to reduce alcohol craving and relapses and facilitate alcoholism cessation.

Keywords: alcohol dependence; craving; dorsolateral prefrontal cortex; relapses; tDCS.

Figures

Figure 1
Figure 1
Diagram of the general procedure: eligible Alcohol Use Disorder (AUD) patients were recruited from clinics for treatment of drug dependence, signed the Term of Consent and were randomized to receive repetitive bilateral (cathode left/anode right over the dorsolateral Prefrontal Cortex) transcranial Direct Current Stimulation (tDCS, 2 mA, 35 cm2, stimulation for 20 min) or placebo (sham-tDCS) every other day in a total of 10 sessions. Craving to the use of alcohol was examined by 5 items from the Obsessive-Compulsive Drinking Scale (OCDS) once a week for 5 weeks (the week before treatment, during the second, third and fourth treatment weeks, and the week after treatment). A, anterior; P, posterior; R, right; L, left; a, anode; c, cathode; BS, brain stimulation.
Figure 2
Figure 2
Flow diagram according to CONSORT 2010.
Figure 3
Figure 3
Craving is shown as the 5-items from the Obsessive-Compulsive Drinking Scale (OCDS) scores in the week before treatment (1 initial), the second (2), third (3) and fourth (4) weeks during the treatment, and the week after treatment (5 final) with bilateral repetitive transcranial Direct Current Stimulation (tDCS, 2 mA, 35 cm2: cathode left/anode right over the dorsolateral Prefrontal Cortex; stimulation for 20 min every other day in a total of 10 sessions; n = 23) or placebo (sham-tDCS; n = 22) in Alcohol Use Disorder (AUD) patients individually (A for sham-tDCS; B for tDCS subjects) and by their mean scores ± standard error of means (S.E.M.) (C). Linear regression for sham-tDCS: *p < 0.05; Linear regression for the real tDCS group: **p < 0.005, slope difference: **p < 0.005. Mean scores of craving depicted in the week before and the week after treatment in the real and sham-tDCS groups are shown in (D). ***p = 0.0005 when compared to baseline craving in the real tDCS group (paired t-test).
Figure 4
Figure 4
Alcohol use relapses in alcohol use disorder (AUD) patients in the 3 months follow-up after 10 sessions of sham- (n = 18) or real tDCS (n = 22) applied over the bilateral dorsolateral Prefrontal Cortex. **p = 0.01 (Fisher's exact test).

References

    1. Anton R. F. (2000). Obsessive-compulsive aspects of craving: development of the obsessive compulsive drinking scale. Addiction 95 (Suppl. 2), S211–S217. 10.1046/j.1360-0443.95.8s2.9.x
    1. Anton R. F., Moak D. H., Latham P. (1995). The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol. Clin. Exp. Res. 19, 92–99. 10.1111/j.1530-0277.1995.tb01475.x
    1. Anton R. F., Moak D. H., Latham P. K. (1996). The obsessive compulsive drinking scale: a new method of assessing outcome in alcoholism treatment studies. Arch. Gen. Psychiatry 53, 225–231. 10.1001/archpsyc.1996.01830030047008
    1. Batista E. K., Klauss J., Fregni F., Nitsche M. A., Nakamura-Palacios E. M. (2015). A randomized placebo-controlled trial of targeted prefrontal cortex modulation with bilateral tDCS in patients with crack-cocaine dependence. Int. J. Neuropsychopharmacol. 18:pyv066. 10.1093/ijnp/pyv066
    1. Boggio P. S., Sultani N., Fecteau S., Merabet L., Mecca T., Pascual-Leone A., et al. . (2008). Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. Drug Alcohol Depend. 92, 55–60. 10.1016/j.drugalcdep.2007.06.011
    1. Brunoni A. R., Amadera J., Berbel B., Volz M. S., Rizzerio B. G., Fregni F. (2011). A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int. J. Neuropsychopharmacol. 14, 1133–1145. 10.1017/S1461145710001690
    1. Cohen J. (1992). A power primer. Psychol. Bull. 112, 155–159. 10.1037/0033-2909.112.1.155
    1. Daley D. C. (2013). Family and social aspects of substance use disorders and treatment. J. Food Drug. Anal. 21, S73–S76. 10.1016/j.jfda.2013.09.038
    1. da Silva M. C., Conti C. L., Klauss J., Alves L. G., Do Nascimento Cavalcante H. M., Fregni F., et al. . (2013). Behavioral effects of transcranial direct current stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence. J. Physiol. Paris 107, 493–502. 10.1016/j.jphysparis.2013.07.003
    1. den Uyl T. E., Gladwin T. E., Rinck M., Lindenmeyer J., Wiers R. W. (2016). A clinical trial with combined transcranial direct current stimulation and alcohol approach bias retraining. Addict. Biol. 22, 1632–1640. 10.1111/adb.12463
    1. Den Uyl T. E., Gladwin T. E., Wiers R. W. (2015). Transcranial direct current stimulation, implicit alcohol associations and craving. Biol. Psychol. 105, 37–42. 10.1016/j.biopsycho.2014.12.004
    1. de Wildt W. A., Lehert P., Schippers G. M., Nakovics H., Mann K., Van Den Brink W. (2005). Investigating the structure of craving using structural equation modeling in analysis of the obsessive-compulsive drinking scale: a multinational study. Alcohol. Clin. Exp. Res. 29, 509–516. 10.1097/01.ALC.0000158844.35608.48
    1. DSM-5 (2013). Diagnostic and Statistical Manual of Mental Disorders : DSM-5. Washington, DC: American Psychiatric Association.
    1. Fregni F., Liguori P., Fecteau S., Nitsche M. A., Pascual-Leone A., Boggio P. S. (2008). Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study. J. Clin. Psychiatry 69, 32–40. 10.4088/JCP.v69n0105
    1. Gardner E. L. (2011). Addiction and brain reward and antireward pathways. Adv. Psychosom. Med. 30, 22–60. 10.1159/000324065
    1. Goldman R. L., Borckardt J. J., Frohman H. A., O'neil P. M., Madan A., Campbell L. K., et al. . (2011). Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving. Appetite 56, 741–746. 10.1016/j.appet.2011.02.013
    1. Grall-Bronnec M., Sauvaget A. (2014). The use of repetitive transcranial magnetic stimulation for modulating craving and addictive behaviours: a critical literature review of efficacy, technical and methodological considerations. Neurosci. Biobehav. Rev. 47, 592–613. 10.1016/j.neubiorev.2014.10.013
    1. Heinz A., Beck A., Grusser S. M., Grace A. A., Wrase J. (2009). Identifying the neural circuitry of alcohol craving and relapse vulnerability. Addict. Biol. 14, 108–118. 10.1111/j.1369-1600.2008.00136.x
    1. Higgins E. S., George M. S. (2009). Brain Stimulation Therapies for Clinicians. Washington, DC: American Psychiatric Pub.
    1. Jansen J. M., Daams J. G., Koeter M. W., Veltman D. J., Van Den Brink W., Goudriaan A. E. (2013). Effects of non-invasive neurostimulation on craving: a meta-analysis. Neurosci. Biobehav. Rev. 37, 2472–2480. 10.1016/j.neubiorev.2013.07.009
    1. Kalivas P. W., Volkow N. D. (2005). The neural basis of addiction: a pathology of motivation and choice. Am. J. Psychiatry 162, 1403–1413. 10.1176/appi.ajp.162.8.1403
    1. Klauss J., Penido Pinheiro L. C., Silva Merlo B. L., Correia Santos Gde A., Fregni F., Nitsche M. A., et al. . (2014). A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence. Int. J. Neuropsychopharmacol. 17, 1793–1803. 10.1017/S1461145714000984
    1. Koob G. F., Volkow N. D. (2016). Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry 3, 760–773. 10.1016/S2215-0366(16)00104-8
    1. Kuo M. F., Paulus W., Nitsche M. A. (2014). Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases. Neuroimage 85 (Pt 3), 948–960. 10.1016/j.neuroimage.2013.05.117
    1. Lakens D. (2013). Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front. Psychol. 4:863. 10.3389/fpsyg.2013.00863
    1. Lupi M., Martinotti G., Santacroce R., Cinosi E., Carlucci M., Marini S., et al. . (2017). Transcranial direct current stimulation in substance use disorders: a systematic review of scientific literature. J. ECT 33, 203–209. 10.1097/YCT.0000000000000401
    1. Miller P. M., Book S. W., Stewart S. H. (2011). Medical treatment of alcohol dependence: a systematic review. Int. J. Psychiatry Med. 42, 227–266. 10.2190/PM.42.3.b
    1. Nitsche M. A., Cohen L. G., Wassermann E. M., Priori A., Lang N., Antal A., et al. . (2008). Transcranial direct current stimulation: state of the art 2008. Brain Stimul. 1, 206–223. 10.1016/j.brs.2008.06.004
    1. O'brien C. (2011). Addiction and dependence in DSM-V. Addiction 106, 866–867. 10.1111/j.1360-0443.2010.03144.x
    1. Preti A., Muscio C., Boccardi M., Lorenzi M., De Girolamo G., Frisoni G. (2014). Impact of alcohol consumption in healthy adults: a magnetic resonance imaging investigation. Psychiatry Res. 224, 96–103. 10.1016/j.pscychresns.2014.06.005
    1. Robinson T. E., Berridge K. C. (1993). The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res. 18, 247–291. 10.1016/0165-0173(93)90013-P
    1. Self D. W. (1998). Neural substrates of drug craving and relapse in drug addiction. Ann. Med. 30, 379–389. 10.3109/07853899809029938
    1. Valle A., Roizenblatt S., Botte S., Zaghi S., Riberto M., Tufik S., et al. . (2009). Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial. J. Pain Manag. 2, 353–361.
    1. Vetulani J. (2001). Drug addiction. Part II. Neurobiology of addiction. Pol. J. Pharmacol. 53, 303–317.
    1. Volkow N. D., Wang G. J., Fowler J. S., Tomasi D., Telang F. (2011). Addiction: beyond dopamine reward circuitry. Proc. Natl. Acad. Sci. U.S.A. 108, 15037–15042. 10.1073/pnas.1010654108
    1. Weiss F. (2005). Neurobiology of craving, conditioned reward and relapse. Curr. Opin. Pharmacol. 5, 9–19. 10.1016/j.coph.2004.11.001
    1. Wilson S. J., Sayette M. A., Fiez J. A. (2004). Prefrontal responses to drug cues: a neurocognitive analysis. Nat. Neurosci. 7, 211–214. 10.1038/nn1200
    1. Zar J. H. (1984). Biostatistical analysis. Englewood Cliffs, NJ: Prentice-Hall.

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