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Martin Bares,1,2 Martin Brunovsky,1,2 Pavla Stopkova,1,2 Martin Hejzlar,1,2 Tomas Novak1,2 1NIMH Clinical Center, National Institute of Mental Health Czech Republic, Topolova 748, Klecany, Czech Republic; 2The Department of Psychiatry and Medical Psychology, 3rd Faculty of Medicine, Charles University, Prague, Czech RepublicCorrespondence: Martin BaresNational Institute of Mental Health, Topolova 748, Klecany, Czech RepublicTel +4 202 6600 3330Fax +4 202 8308 8420Email martin.bares@nudz.czObjective: Transcranial direct-current stimulation (tDCS), a relatively new neuromodulation approach, provides some evidence of an antidepressant effect. This randomized, 4-week, double-blind study with 8-week, open-label, follow-up compared the efficacy and tolerability of left anodal tDCS with venlafaxine ER (VNF) in the treatment of depression and prevention of early relapse.Methods: Subjects (n = 57) received tDCS (2 mA, 20 sessions, 30 mins) plus placebo (n = 29) or VNF plus sham tDCS (n = 28). Responders to both interventions entered the open-label follow-up. The primary outcome was score change in the Montgomery–Åsberg Depression Rating Scale (MADRS) at week 4 of the study. Secondary outcomes were response, remission, dropout rates and relapse rates within the follow-up.The mean change in the MADRS score from baseline to week for patients treated with tDCS was 7.69 (95% CI, 5.09–10.29) points and 9.64 (95% CI, 6.20–13.09) points for patients from the VNF group, a nonsignificant difference (1.95, 95% CI −2.25–6.16; t (55) = 0.93, p= 0.36, Cohen´s d = 0.24). There were no significant between-group differences in the MADRS scores from baseline to endpoint (intention-to-treat analysis). The response/remission rate for tDCS (24%/17%) and VNF (43%/32%) as well as the dropout rate (tDCS/VNF; 6/6) did not differ significantly between groups. In the follow-up, relapse (tDCS/VNF; 1/2) and dropout (tDCS/VNF; 2/3) rates were low and comparable.Limitations: A relatively small sample size and short duration of the antidepressant treatment; no placebo arm.Conclusion: Overall, this study found a similar efficacy of tDCS and VNF in the acute treatment of depression and prevention of early relapse. The real clinical usefulness of tDCS and its optimal parameters in the treatment of depression should be further validated.Keywords: transcranial direct-current stimulation, tDCS, depression, venlafaxine ER, treatment

Background There are no head-to-head studies comparing the antidepressant effect of transcranial direct current stimulation (tDCS) with repetitive transcranial magnetic stimulation (rTMS). This pooled analysis compared indirectly the antidepressant efficacy and acceptability of rTMS, tDCS, and the antidepressant venlafaxine (VNF) extended-release. Methods The analysis (n=117, both patients with treatment-resistant depression (TRD) and non-TRD were included) examined pooled data from two 4-week, single-centered, two-armed, double-blind, randomized studies (EUDRACT n. 2005-000826-22 and EUDRACT n. 2015-001639-19). The antidepressant efficacy of right-sided low-frequency rTMS (n=29) vs VNF (n=31) and left-sided anodal tDCS (n=29) vs VNF (n=28) was evaluated. The primary outcome was a change in the Montgomery–Asberg Depression Rating Scale (MADRS) score from baseline to the treatment endpoint at week 4. The response was defined as a ≥50% reduction in the MADRS score and remission as the MADRS score ≤10 points, both were calculated for the primary treatment endpoint at week 4. Results Mean change in total MADRS scores from baseline to week 4 was 7.0 (95% CI, 4.8–9.1) points in the rTMS group, 7.6 (95% CI, 5.5–9.8) in the tDCS group, and 8.9 (95% CI, 7.4–10.4) among patients in the VNF group, a non-significant difference (F(2111)=0.62, p=0.54). Similarly, neither the response rates nor remission rates for rTMS (response 31%; remission 17%), tDCS (24%, 17%), or VNF (41%; 27%) significantly differed among treatment groups ( χ 2=2.59, p=0.28; χ 2=1.66, p=0.44). Twenty patients (17%) dropped out of the studies in a similar proportion across groups (rTMS 3/29, tDCS 6/29, VNF 11/59, χ 2=1.41, p=0.52). Conclusion Our current analysis found a comparable efficacy and acceptability in all three treatment modalities (rTMS, tDCS, and VNF) and clinical relevance for the acute treatment of major depressive disorder.

Stigmatization of people with mental illness in health care is a serious problem contributing to poor provision of health care and preventive medicine, it decreases their willingness to seek help and reduces quality of their life and life expectancy. The aim of this study is to evaluate the impact of the anti-stigma training READ on medical students during their psychiatric module. The training was held by a psychiatrist and a peer lecturer. This study is a part of the international project INDIGO. A total of 53 medical students participated in this study (32 in intervention group, 21 in control group). Participants completed questionnaire at baseline and at immediate follow-up. It contained scales measuring attitudes, knowledge, empathy and intergroup anxiety. The intervention group demonstrated reductions in stigma-related attitudes, improvements in mental illness knowledge and reductions in intergroup anxiety. At immediate follow-up the control group demonstrated improvements in mental illness knowledge and reductions in intergroup anxiety. Based on the results of this study common psychiatric module at the medical school (including theoretical and practical education) does not contribute to the sufficient reduction of stigma. The training READ with an involvement of peer lecturers appears to be a convenient instrument how to reduce stigmatization of people with mental illness at medical schools. The contact with people who are not in the acute state of the illness is crucial for destigmatization.

Background The study evaluated the effectiveness of EEG alpha 1, alpha 2 and theta power, along with prefrontal theta cordance (PFC), frontal and occipital alpha 1, alpha 2 asymmetry (FAA1/2, OAA1/2) at baseline and their changes at week 1 in predicting response to antidepressants. Method: Resting-state EEG data were recorded from 103 depressive patients that were treated in average for 5.1 ± 0.9 weeks with SSRIs (n = 57) and SNRIs (n = 46). Results Fifty-five percent of patients (n = 56) responded to treatment (i.e.reduction of Montgomery-Asberg Depression Rating Scale score ≥ 50%) and 45% (n = 47) of treated subjects did not reach positive treatment outcome. No differences in EEG baseline alpha and theta power or changes at week 1 for prefrontal, frontal, central, temporal and occipital regions were found between responders and non-responders. Both groups showed no differences at baseline PFC, FAA1/2 and OAA1/2 as well as change of FAA1/2 at week 1. The only parameters associated with treatment outcome were decrease of PFC in responders and increase of OAA1/2 at week 1 in non-responders. There was no influence of the used antidepressant classes on the results. The PFC change at week 1 (PFCC) (area under curve-AUC = 0.75) showed only a numerically higher predictive ability than OAA change in alpha 1 (OAA1C, AUC = 0.64)/alpha 2 (OAA2C, AUC = 0.63). A combined model, where OAA1C was added to PFCC (AUC = 0.79), did not significantly improve response prediction. Conclusion Besides PFCC, we found that OAA1C/OAA2C might be another candidate for EEG predictors of antidepressant response.

IntroductionRepetitive transcranial magnetic stimulation (rTMS) has important role in treatment of neuropsychiatric disorders. Theta burst stimulation (TBS), a modification of rTMS, seems to produce greater changes in cortical excitability (CE) than those observed in conventional rTMS protocols. TBS is used in different protocols: intermittent TBS (iTBS) and continuous TBS (cTBS). While iTBS facilitates CE, cTBS leads to CE inhibition. However, a prolonged cTBS produces facilitatory effect similar to that of iTBS. Prolonged TBS (pTBS), a novel rTMS paradigm, is of great clinical interest for its short duration, but also because it may induce stronger effect.AimTo prove the effect of pTBS of motor cortex on changes of motor threshold (MT), CE and pain threshold (PT) in healthy volunteers (HV). To compare the effects of two different forms of active pTBS (pcTBS, piTBS) with placebo.MethodsA double-blind, placebo-controlled, cross-over study compared the effects of different pTBS of contralateral M1 area on MT, CE and PT. We enrolled 24 HV to the study, who underwent all types of pTBS in randomized order and were assessed before and after each pTBS application. We used MagPro R30 (with coil focused to contralateral M1 area, 1200 pulses/session, 90% MT).ResultsA significant changes in CE and MT were found after application of continuous pTBS. Intermittent and placebo pTBS did not confirm the effect. There were no significant changes on PT after pTBS. Continuous pTBS was better tolerated than intermittent pTBS.ConclusionpTBS should be considered as an effective and safe treatment option for neuropsychiatric disorders.Disclosure of interestSupported by AZV 16-31380A.