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Over the past decade, theta-burst stimulation (TBS) has become a focus of interest in neurostimulatory research. Compared to conventional repetitive transcranial magnetic stimulation (rTMS), TBS produces more robust changes in cortical excitability (CE). There is also some evidence of an analgesic effect of the method. Previously published studies have suggested that different TBS parameters elicit opposite effects of TBS on CE. While intermittent TBS (iTBS) facilitates CE, continuous TBS (cTBS) attenuates it. However, prolonged TBS (pTBS) with twice the number of stimuli produces the opposite effect. In a double-blind, placebo-controlled, cross-over study with healthy subjects ( n = 24), we investigated the effects of various pTBS (cTBS, iTBS, and placebo TBS) over the right motor cortex on CE and pain perception. Changes in resting motor thresholds (RMTs) and absolute motor-evoked potential (MEP) amplitudes were assessed before and at two time-points (0–5 min; 40–45 min) after pTBS. Tactile and thermal pain thresholds were measured before and 5 min after application. Compared to the placebo, prolonged cTBS (pcTBS) transiently increased MEP amplitudes, while no significant changes were found after prolonged iTBS. However, the facilitation of CE after pcTBS did not induce a parallel analgesic effect. We confirmed that pcTBS with twice the duration converts the conventional inhibitory effect into a facilitatory one. Despite the short-term boost of CE following pcTBS, a corresponding analgesic effect was not demonstrated. Therefore, the results indicate a more complex regulation of pain, which cannot be explained entirely by the modulation of excitability.

ObjectiveTranscranial 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.MethodsSubjects (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. LimitationsA relatively small sample size and short duration of the antidepressant treatment; no placebo arm.ConclusionOverall, 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.

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–Åsberg 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.

Introduction and objectivesPrevious studies demonstrated efficacy of reduction of QEEG prefrontal theta cordance (RC) after the first week of treatment in the prediction of antidepressant response.AimsThe study aimed to compare the ability of RC in the prediction of response to various antidepressant classes.MethodsAll patients (n = 142) were treated with antidepressants (SSRI-58, SNRI-47, NDRI-22, NaSSA-15) for ≥ 4 weeks. Response was defined as MADRS reduction ≥ 50%. EEG were performed at baseline and week 1 of treatment and cordance was calculated for 3 prefrontal electrodes (Fp1, Fp2, Fz).ResultsLogistic regression identified RC as a predictor of response to SSRI, SNRI and NDRI but not for NaSSA. Predictive parameters of RC for response to mentioned antidepressant classes are displayed in the Table 1.Areas under curves of ROC analysis (AUC) of RC for response prediction were not significantly different among antidepressant classes.ConclusionThe predictive efficacy of RC for response to SSRI, SNRI and NDRI was comparable.This study was supported by the grants of MH CZ nr.15-29900A, MH CZ – DRO (NIMH-CZ, 00023752) and by the project Nr. LO1611 from the MEYS under the NPU I program.

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.

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