Multiple Sessions of High-Frequency Repetitive Transcranial Magnetic Stimulation as a Potential Treatment for Gambling Addiction: A 3-Month, Feasibility Study.

Gambling disorder (GD) is a behavioral addiction, in which dysfunctions in prefrontal activity have been proposed as relevant pathophysiological correlates. The aim of the present study was to preliminarily investigate the feasibility of a noninvasive neuromodulation intervention targeting the prefrontal cortex to treat GD in an open-label setting. We included 8 treatment-seeking patients with GD (7 males; 1 female; mean age: 40.6 ± 11.2). The study consisted of 3 phases: (1) outpatient screening phase, (2) 2-week intensive repetitive transcranial magnetic stimulation (rTMS) treatment phase (twice daily, 5 days/week for 2 weeks); and (3) 3-month maintenance follow-up phase (twice daily, once a week). Each high-frequency (15 Hz) rTMS session was delivered targeting the left dorsolateral prefrontal cortex. GD severity and treatment response were assessed at the baseline and during the follow-up. No relevant side effect was reported. We found a 71.2% Gambling Symptom Assessment Scale mean score reduction after 2 weeks of rTMS treatment; the days spent gambling decreased from 19.63 ± 7.96 to 0.13 ± 0.35 days. Clinical improvements were maintained throughout the study period. The lack of a control group limits the interpretation of these results. In conclusion, these results consolidate the rationale that rTMS interventions deserve further investigation as a potential treatment for GD. These protocols should be tested in larger randomized controlled studies, to determine the real benefits of neuromodulation in the clinical course of patients with GD. Registration Number: ClinicalTrials.gov Identifier NCT03336879.

Repetitive transcranial magnetic stimulation in treatment-seeking subjects with cocaine use disorder: A randomized, double-blind, sham-controlled trial.

BACKGROUND: Cocaine use disorder (CUD) is a chronic and relapsing brain disorder with no approved treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in open label and single-blind studies, reducing cocaine craving and consumption. Although, large randomized, double-blind, controlled trials are still missing. OBJECTIVE: This multi-center, randomized, double-blind, sham-controlled study was designed to evaluate the safety and efficacy of multiple sessions of active rTMS compared to sham stimulation in patients with CUD. METHODS: rTMS (15 Hz, 2 daily sessions for 5 days/week,for a total of 20 stimulation sessions) was delivered over the left DLPFC for two weeks of continuous treatment followed by 12 weeks of maintenance (1 day/week, twice a day), in a double-blind, randomized sham-controlled design. Our primary outcomes included self-reported cue-induced craving and cocaine consumption, as measured by percentage of negative urine tests. Our secondary outcomes included: 1) changes in depressive symptoms; 2) changes in cocaine withdrawal symptoms; and 3) changes in self-reported days of cocaine use. RESULTS: Forty-two outpatients with CUD were enrolled in the active rTMS group and 38 patients in the sham group. We observed a significant decrease in self-reported cue-induced cocaine craving and consumption in both the active rTMS and sham, whereas no main effect of treatment was found. However, the active rTMS group showed greater changes in depressive symptoms. The improvement on depressive symptomatology was particularly marked among patients receiving a total number of rTMS sessions greater than 40 and those reporting more severe depressive symptoms at baseline. CONCLUSIONS: A significant improvement of CUD symptoms during active rTMS treatment was observed. However, we did not observe significant differences in cocaine craving and consumption between treatment groups, highlighting the complexity of factors contributing to CUD maintenance. A significant improvement in depressive symptoms was observed in favour of the active group. Clinical trial registration details:clinicaltrials.govidentifierNCT03333460.

rTMS Reduces Psychopathological Burden and Cocaine Consumption in Treatment-Seeking Subjects With Cocaine Use Disorder: An Open Label, Feasibility Study.

Introduction: Cocaine use disorder (CUD) currently represents a notable public health concern, linked with significant disability, high chances of chronicity, and lack of effective pharmacological or psychological treatments. Repetitive transcranial magnetic stimulation (rTMS) is supposed to be a potential therapeutic option for addictive disorders. Aim of this study was to evaluate the feasibility of rTMS on (1) cocaine craving and consumption and (2) other comorbid psychiatric symptoms. Methods: Twenty treatment seeking CUD subjects underwent 2 weeks of intensive rTMS treatment (15Hz; 5 days/week, twice a day for a total of 20 stimulation sessions) of the left dorsolateral prefrontal cortex, followed by 2 weeks of maintenance treatment (15Hz, 1 day/week, twice a day). Sixteen patients completed the study. Patients were evaluated at baseline (T0), after 2 weeks of treatment (T1), and at the end of the study (T2; 4 weeks), with the following scales: Cocaine Selective Severity Assessment (CSSA), Zung Self-Rating Anxiety Scale, Beck Depression Inventory (BDI), Symptom Checklist-90 (SCL-90), and the Insomnia Severity Index. Results: After four weeks of rTMS treatment, 9 out of 16 subjects (56.25%) had a negative urinalysis test, with a significant conversion rate with respect to baseline (Z = -3.00; p = 0.003). Craving scores significantly improved only at T2 (p = 0.020). The overall psychopathological burden, as measured by the SCL-90 Global Severity Index (GSI), significantly decreased during the study period (Z = -2.689; p = 0.007), with a relevant improvement with regards to depressive symptoms, anhedonia, and anxiety. Subjects exhibiting lower baseline scores on the SCL-90 were more likely to be in the positive outcome group at the end of the study (Z = -3.334; p = 0.001). Discussion: Findings from this study are consistent with previous contributions on rTMS use in subjects with cocaine use disorder. We evidenced a specific action on some psychopathological areas and a consequent indirect effect in terms of relapse prevention and craving reduction. A double-blind, sham-controlled, neuro-navigated rTMS study design is needed, in order to confirm the potential benefits of this technique, opening new scenarios in substance use disorders treatment.

Internet addiction: hours spent online, behaviors and psychological symptoms.

OBJECTIVE: The aim of this study was to investigate psychopathological symptoms, behaviors and hours spent online in patients with internet addiction disorder (IAD) at a new psychiatric service for IAD inside a policlinic. METHOD: Eighty-six subjects participated in the study. Thirty-three patients asking for psychiatric consultation regarding their excessive use of the internet were assessed with IAD interview, internet addiction test (IAT), Symptom Checklist-90-Revised (SCL-90-R) and a brief sociodemographic survey. Moreover, patients had to respond to the following question: Over the last month, how much time have you spent online per week? At the end of psychiatric assessment, 21 of the 33 patients satisfied inclusion (IAD interview) and exclusion (psychotic disorders, neurocognitive deficits, dementia, serious mental delay, current alcohol or drug abuse) criteria. Twenty-one patients of the clinical group were compared with 65 subjects of a control group who were recruited online using IAT. RESULTS: IAD patients showed significantly higher scores on the IAT compared to subjects of the control group. Only item 7 (How often do you check your e-mail before something else that you need to do?) showed a significant inverse trend. SCL-90-R anxiety and depression subscale scores and item 19 (How often do you choose to spend more time online over going out with others?) of the IAT were positively correlated with number of weekly hours spent online in IAD patients. CONCLUSION: Findings suggest that a misuse of internet, characterized by many hours spent online avoiding interpersonal relationships with real and known people, could be an important criterion in the clinical interview in order to diagnose the IAD. The association between the lost interest in communicating with real people and psychological symptoms such as anxiety and depression could be relevant to detect IAD patients.

Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects.

OBJECTIVE: Aim of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of Acetyl-l-Carnitine (ALC), at different dosages, on specific anhedonic symptoms in detoxified alcohol dependent subjects. Secondary endpoints were the effect of ALC on melancholic and negative symptoms. METHOD: Sixty-four anhedonic alcohol dependent patients with minor or absent withdrawal symptoms were randomized: 23 received ALC at a dosage of 3g/day, 21 received ALC at a dosage of 1g/day, and 20 were given placebo. ALC was given intravenously for 10days, followed by 80days of oral treatment plus a follow-up period of 45days. The presence of anhedonic symptoms was determined by the SHAPS (Snaith-Hamilton Pleasure Scale) and the VASa (Visual Analogue Scale for Anhedonia); negative and melancholic symptoms were evaluated by the SANS (Scale for the Assessment of Negative Symptoms), and the BRMS (Bech-Rafaelsen Melancholia Scale). RESULTS: The natural course of anhedonia in the placebo group showed a decline until day 30 and remains stable for the rest of the study. Intravenously ALC accelerated the improvement of anhedonia reaching constant low levels early, on day 10. At this step levels of anhedonia (SHAPS, VASa) and melancholic symptoms (BRMES) resulted significantly reduced (p<0.05) in both the ALC 3g and ALC 1g groups with respect to placebo; SANS scores significantly reduced only in the ALC 1g respect to placebo (p=0.014). During oral treatment with ALC, anhedonia scores did not differ from placebo. CONCLUSION: Intravenously ALC was effective in accelerating the abstinence-associated improvement of anhedonia, melancholic and negative symptoms, whereas oral ALC treatment starting on day 10 showed no further improvements. Accordingly, in alcohol dependent subjects, ALC may be considered as a new potentially useful drug for the treatment of anhedonia.