LETTER TO THE EDITOR
Effect of a Ten-Day Prefrontal Transcranial Direct Current Stimulation Protocol for Crack Craving A Proof-of-Concept Trial To the Editor: he dorsolateral prefrontal cortex (DLPFC) plays a role in craving through its modulatory effects over the reward system. In fact, diminished functioning of the DLPFC is present in substance addiction. Recently, transcranial magnetic stimulation (rTMS) has been tested in clinical research for modulating the prefrontal cortex to reduce cocaine1 and cigarette2 craving. The effects of neuromodulation strategies, however, have not been evaluated for crack craving hitherto. We performed an open-label trial with patients diagnosed with crack addiction who underwent a 10-day transcranial direct current stimulation (tDCS) prefrontal protocol. The anode was positioned over the left DLPFC, and the cathode was positioned contralaterally.3 The electrode was mounted on the DLPFC and localized using the Beam F3 System program that uses a computerized process for localizing the specific area for the electrode according to 3 distinct measurements: the nasion-to-inion distance, the distance from the left preaurical point to the right preaurical point, and the circumference at the level of the eyebrow, passing over the inion. The F3 location will be calculated by the program as the distance between the vertex and the intersection between the 2 first distances. We used a direct current of 2.0 mA for 20 minutes. Elected patients agreed with a previously institutional review board-approved informed consent. Patients with psychiatric comorbidity were excluded. Crack craving was assessed with the Cocaine Craving Questionnaire-Brief (CCQB). At baseline and final sessions, patients were exposed to neutral crack images (photos of the substance itself and accessories such as a crack pipe) to induce craving.4 The primary outcome was analyzed continuously as the mean reduction between the baseline and final CCQB scores. Every patient was drug-free for at least 3 months. No pharmacological treatment protocol was in use. The CCQB is
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composed of 10 questions, with scores from 01 to 07. The score 01 corresponds to “totally disagree” and the score 07 to “totally agree.” Questions were elaborated dealing on the patient's wish to smoke crack and the craving intensity. The higher the wish for consumption, the higher the score. Questions 04 and 07 were excluded from the final score because they consider the smaller score for the higher wish. In the end, the sum of scores from all questions is directly associated to the level of craving. A total of 11 patients were included. Inclusion criteria encompassed the following: patients aged from 18 to 59 years, men or women, and diagnosed as crack/ cocaine dependents according to the diagnosis criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition/American Psychiatric Association. Patients should be abstinent for at least 3 weeks. Exclusion criteria comprised the following: patients with other axis 1 diagnoses (except for alcohol, tobacco, and marijuana addiction, usually seen along crack/cocaine dependence), patients with neurological or severe clinical conditions, patients with strong suicidal ideation, pregnancy, and specific tDCS contraindications (ie, skull metal plates or anatomic alterations). At baseline, patients presented with a mean (SD) age of 37.8 (7.7) years; all patients were men. Mean (SD) baseline CCQB scores were 20.18 (13.8); anxiety symptoms, as assessed by the Beck Anxiety Inventory, were 8.8 (6.8); and cognitive performance at baseline was 20 (3.2), as assessed by the Montreal Cognitive Assessment (MoCA). Considering the primary outcome, there was a mean (SD) reduction of 7.19 (2.18) points in the CCQB with statistical significance (t10 = 3.28; P = 0.0082; 95% confidence interval, 2.31–12.05). We found no significant difference for anxiety symptoms and cognitive performance (P = 0.624 and P = 0.161, respectively). To verify the influence of either clinical or demographical variables over clinical effect, we performed multiple regressions regarding age, baseline severity scores, time since diagnosis, and anxiety symptoms. We found no significant confounder in our analysis. Our positive results are in consonance with previous studies. In fact, a recent meta-analysis on 17 eligible studies on both
Journal of ECT • Volume 00, Number 00, Month 2016
rTMS and tDCS for drug and high-palatable craving revealed a pooled standardized effect size (Hedges' g) of 0.476 (confidence interval, 0.316–0.636), indicating a mediumeffect size favoring active noninvasive neurostimulation over sham stimulation in the reduction of craving (z = 5.832, P < 0.001). No significant differences were found between rTMS and tDCS.5 Our study's limitations include the small sample size, which may impair internal validity, its unblinded nature, lack of a control group, and short length. Moreover, our results may be overestimated due to intrinsic characteristics such as the placebo effect and the Hawthorne effect. We understand that the trends seen in the completers shall strongly justify a larger double-blind study with better estimation of sample size. Rodrigo de Almeida Ramos, MD Ivan Taiar, PT Alisson Paulino Trevizol, MD Pedro Shiozawa, MD, PhD Quirino Cordeiro, MD, PhD Interdisciplinary Center for Clinical Neuromodulation Psychiatry Department Santa Casa School of Medical Sciences São Paulo, Brazil [email protected]
The authors have no conflicts of interest or financial disclosures to report. REFERENCES 1. Politi E, Fauci E, Santoro A, et al. Daily sessions of transcranial magnetic stimulation to the left prefrontal cortex gradually reduce cocaine craving. Am J Addict. 2008;17:345–346. 2. Amiaz R, Levy D, Vainiger D, et al. Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. Addiction. 2009;104:653–660. 3. Bikson M, Rahman A, Datta A. Computational models of transcranial direct current stimulation. Clin EEG Neurosci. 2012;43:176–183. 4. Kosten TR, Scanley BE, Tucker KA, et al. Cue-induced brain activity changes and relapse in cocaine-dependent patients. Neuropsychopharmacology. 2006;31:644–650. 5. Jansen JM, Daams JG, Koeter MW, et al. Effects of non-invasive neurostimulation on craving: a meta-analysis. Neurosci Biobehav Rev. 2013; 37(10 Pt 2):2472–2480.
www.ectjournal.com
Copyright © 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
1
Effect of a Ten-Day Prefrontal Transcranial Direct Current Stimulation Protocol for Crack Craving A Proof-of-Concept Trial To the Editor: he dorsolateral prefrontal cortex (DLPFC) plays a role in craving through its modulatory effects over the reward system. In fact, diminished functioning of the DLPFC is present in substance addiction. Recently, transcranial magnetic stimulation (rTMS) has been tested in clinical research for modulating the prefrontal cortex to reduce cocaine1 and cigarette2 craving. The effects of neuromodulation strategies, however, have not been evaluated for crack craving hitherto. We performed an open-label trial with patients diagnosed with crack addiction who underwent a 10-day transcranial direct current stimulation (tDCS) prefrontal protocol. The anode was positioned over the left DLPFC, and the cathode was positioned contralaterally.3 The electrode was mounted on the DLPFC and localized using the Beam F3 System program that uses a computerized process for localizing the specific area for the electrode according to 3 distinct measurements: the nasion-to-inion distance, the distance from the left preaurical point to the right preaurical point, and the circumference at the level of the eyebrow, passing over the inion. The F3 location will be calculated by the program as the distance between the vertex and the intersection between the 2 first distances. We used a direct current of 2.0 mA for 20 minutes. Elected patients agreed with a previously institutional review board-approved informed consent. Patients with psychiatric comorbidity were excluded. Crack craving was assessed with the Cocaine Craving Questionnaire-Brief (CCQB). At baseline and final sessions, patients were exposed to neutral crack images (photos of the substance itself and accessories such as a crack pipe) to induce craving.4 The primary outcome was analyzed continuously as the mean reduction between the baseline and final CCQB scores. Every patient was drug-free for at least 3 months. No pharmacological treatment protocol was in use. The CCQB is
T
composed of 10 questions, with scores from 01 to 07. The score 01 corresponds to “totally disagree” and the score 07 to “totally agree.” Questions were elaborated dealing on the patient's wish to smoke crack and the craving intensity. The higher the wish for consumption, the higher the score. Questions 04 and 07 were excluded from the final score because they consider the smaller score for the higher wish. In the end, the sum of scores from all questions is directly associated to the level of craving. A total of 11 patients were included. Inclusion criteria encompassed the following: patients aged from 18 to 59 years, men or women, and diagnosed as crack/ cocaine dependents according to the diagnosis criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition/American Psychiatric Association. Patients should be abstinent for at least 3 weeks. Exclusion criteria comprised the following: patients with other axis 1 diagnoses (except for alcohol, tobacco, and marijuana addiction, usually seen along crack/cocaine dependence), patients with neurological or severe clinical conditions, patients with strong suicidal ideation, pregnancy, and specific tDCS contraindications (ie, skull metal plates or anatomic alterations). At baseline, patients presented with a mean (SD) age of 37.8 (7.7) years; all patients were men. Mean (SD) baseline CCQB scores were 20.18 (13.8); anxiety symptoms, as assessed by the Beck Anxiety Inventory, were 8.8 (6.8); and cognitive performance at baseline was 20 (3.2), as assessed by the Montreal Cognitive Assessment (MoCA). Considering the primary outcome, there was a mean (SD) reduction of 7.19 (2.18) points in the CCQB with statistical significance (t10 = 3.28; P = 0.0082; 95% confidence interval, 2.31–12.05). We found no significant difference for anxiety symptoms and cognitive performance (P = 0.624 and P = 0.161, respectively). To verify the influence of either clinical or demographical variables over clinical effect, we performed multiple regressions regarding age, baseline severity scores, time since diagnosis, and anxiety symptoms. We found no significant confounder in our analysis. Our positive results are in consonance with previous studies. In fact, a recent meta-analysis on 17 eligible studies on both
Journal of ECT • Volume 00, Number 00, Month 2016
rTMS and tDCS for drug and high-palatable craving revealed a pooled standardized effect size (Hedges' g) of 0.476 (confidence interval, 0.316–0.636), indicating a mediumeffect size favoring active noninvasive neurostimulation over sham stimulation in the reduction of craving (z = 5.832, P < 0.001). No significant differences were found between rTMS and tDCS.5 Our study's limitations include the small sample size, which may impair internal validity, its unblinded nature, lack of a control group, and short length. Moreover, our results may be overestimated due to intrinsic characteristics such as the placebo effect and the Hawthorne effect. We understand that the trends seen in the completers shall strongly justify a larger double-blind study with better estimation of sample size. Rodrigo de Almeida Ramos, MD Ivan Taiar, PT Alisson Paulino Trevizol, MD Pedro Shiozawa, MD, PhD Quirino Cordeiro, MD, PhD Interdisciplinary Center for Clinical Neuromodulation Psychiatry Department Santa Casa School of Medical Sciences São Paulo, Brazil [email protected]
The authors have no conflicts of interest or financial disclosures to report. REFERENCES 1. Politi E, Fauci E, Santoro A, et al. Daily sessions of transcranial magnetic stimulation to the left prefrontal cortex gradually reduce cocaine craving. Am J Addict. 2008;17:345–346. 2. Amiaz R, Levy D, Vainiger D, et al. Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. Addiction. 2009;104:653–660. 3. Bikson M, Rahman A, Datta A. Computational models of transcranial direct current stimulation. Clin EEG Neurosci. 2012;43:176–183. 4. Kosten TR, Scanley BE, Tucker KA, et al. Cue-induced brain activity changes and relapse in cocaine-dependent patients. Neuropsychopharmacology. 2006;31:644–650. 5. Jansen JM, Daams JG, Koeter MW, et al. Effects of non-invasive neurostimulation on craving: a meta-analysis. Neurosci Biobehav Rev. 2013; 37(10 Pt 2):2472–2480.
www.ectjournal.com
Copyright © 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
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