Levkovitz Y, Harel EV, Roth Y, Braw Y, Most D, Katz LN, et al. Deep transcranial magnetic stimulation over the prefrontal cortex: evaluation of antidepressant and cognitive effects in depressive patients. Brain Stimul. 2009;2(4):188-200

Shalvata Mental Health Care Center, Cognitive and Emotional Laboratory, Hod-Hasharon, Israel.
Brain Stimulation (Impact Factor: 4.4). 10/2009; 2(4):188-200. DOI: 10.1016/j.brs.2009.08.002
Source: PubMed


Electroconvulsive therapy (ECT) is an effective alternative for pharmacotherapy in treatment-resistant depressive patients, but the side effects limit its use. Transcranial magnetic stimulation (TMS) has been proposed as a refined alternative, but most studies do not indicate that TMS is as effective as ECT for severe depression.
We propose that the limited effectiveness of standard TMS resides in its superficial effect on the cortex, although much of the pathophysiology of depression is associated with deeper and larger brain regions implicated in the reward system. Herein, we tested the effectiveness and safety of a novel TMS coil, the "H-coil," which enables direct stimulation of deeper brain regions, at the expense of focality.
We have studied the antidepressant and cognitive effects induced by 4 weeks of high-frequency (20 Hz) repeated deep TMS (DTMS) over the prefrontal cortex (PFC) of 65 medication-free depressive patients, who have failed to benefit from prior medications. Patients were randomly assigned to various treatment configurations, differing in stimulation intensity and laterality. Effects were assessed by the 24-item Hamilton depression rating scale (HDRS-24) and several secondary outcome measures.
A significant improvement in HDRS scores was found when high, but not low, stimulation intensity was used. Several cognitive improvements were evident, and no treatment-related serious adverse events were observed.
DTMS over the PFC was found safe and effective in alleviating depression. The results accentuate the significance of deep, high-intensity stimulation over low, and serve as the first study to indicate the potential of DTMS in psychiatric and neurologic disorders.

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Available from: Abraham Zangen, Dec 24, 2013
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    • "Study (by year and first author); country Stim ulati on locat ion Loca tion defin ition Fre que ncy (Hz ) Intens ity (% MT) Coi l typ e Total stimul i Stimu li/sess ion Trai ns/se ssion Inter - train inter val (s) No. of sessi ons Levkovitz et al., 2009; Israel a L 5.5cm 20 120 H1 33600 1680 42 20 20 Rosenberg et al., 2010a; Israel L 5.5cm 20 120 H1 33600 1680 42 20 20 Rosenberg et al., 2010b; Israel L 5.5cm 20 120 H1 33600 1680 42 20 20 Harel et al., 2011; Israel L 5.5cm 20 120 H1 33600 1680 42 20 20 Isserles et al., 2011; Israel b L 5.5cm 20 120 H1 33600 1680 42 20 20 Berlim et al., 2014a "
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    ABSTRACT: Deep transcranial magnetic stimulation (DTMS) is a relatively new, non-invasive method of stimulating larger and, presumably, deeper brain regions. The current study investigated if DTMS delivered with H-coils has acute antidepressant effects in major depression using a systematic literature review and a quantitative meta-analysis. Seventeen studies on 'DTMS or H-coil' and 'depression' were identified on Medline, PsycInfo, and Google Scholar (until November 2014). Data from nine open-label studies were meta-analysed using a random-effects model with inverse-variance weights. The outcome measures were the standardised paired mean difference (Cohen's d) in depression scores on Hamilton Depression Rating Scale (HDRS), response, remission, and dropout rates after acute DTMS treatment compared to baseline. There was a large antidepressant effect after 20 acute, high-frequency DTMS sessions compared to baseline according to HDRS change scores (overall mean weighted d=2.04, 95% confidence interval: 1.53-2.55; nine studies; 150 patients). Overall weighted response, remission, and dropout rates were 60%, 29%, and 18% respectively. HDRS change scores and response rates tended to be higher in four studies with 68 patients on concurrent antidepressants compared to two studies with 26 patients who received DTMS as a monotherapy. These results are based on data from a low number of open-label studies. High-frequency DTMS appears to have acute antidepressant effects after 20 sessions in mostly unipolar and treatment-resistant patients. Concurrent treatment with antidepressants might enhance the efficacy of DTMS. Copyright © 2015. Published by Elsevier B.V.
    Journal of Affective Disorders 08/2015; 187. DOI:10.1016/j.jad.2015.08.033 · 3.38 Impact Factor
    • "Previous protocols have demonstrated its efficacy by inactivating fibres connecting the PFC and the cingulate cortex to the NAc and the VTA. Several clinical studies have documented the effectiveness of deep TMS in drug-resistant depression (Levkovitz et al. 2009; Rosenberg et al. 2010). When administered in accordance with current international guidelines, transcranial magnetic stimulation has been shown to be safe (Levkovitz et al. 2007; Rossi et al. 2009), with few, mild, adverse effects. "
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    ABSTRACT: The hypothalamic pituitary adrenal axis and dopamine have a key role in transition from alcohol social use to addiction. The medial prefrontal cortex was shown to modulate dopaminergic activity and cortisol releasing factor (CRF) release in hypothalamic and extra-hypothalamic systems. The recent advancements in non-invasive neurostimulation technologies has enabled stimulation of deeper brain regions using H-coil transcranial magnetic stimulation (TMS) in humans. This randomized double-blind placebo-controlled pilot study aims to evaluate H-coil efficacy in stimulating the medial prefrontal cortex. Cortisolemia and prolactinemia were evaluated as effectiveness markers. Alcohol intake and craving were considered as secondary outcomes. Eighteen alcoholics were recruited and randomized into 2 homogeneous groups: 9 in the real stimulation group and 9 in the sham stimulation group. Repetitive TMS (rTMS) was administered through a magnetic stimulator over 10 sessions at 20 Hz, directed to the medial prefrontal cortex. rTMS significantly reduced blood cortisol levels and decreased prolactinemia, thus suggesting dopamine increase. Craving visual analogic scale (VAS) in treated patients decreased, as well as mean number of alcoholic drinks/day and drinks on days of maximum alcohol intake (DMAI). In the sham group there was no significant effect observed on cortisolemia, prolactinemia, mean number of alcoholic drinks/day, or drinks/DMAI. Thus, deep rTMS could be considered a potential new treatment for alcoholism.
    Canadian Journal of Physiology and Pharmacology 03/2015; 93(4):1-8. DOI:10.1139/cjpp-2014-0188 · 1.77 Impact Factor
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    • "However, alcohol-related cues which increase craving, are likely to increase activity in the prefrontal cortex (Olbrich et al., 2006). Even with the use of more stringent remission criteria in our study, our results compare favourably with the existing literature of dTMS in MDD (Levkovitz et al., 2009; Rosenberg et al., 2010a, 2010b). The reason could be that our sample was less treatmentresistant than those of previous reports. "
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    ABSTRACT: Introduction: Co-occurrence of Major Depressive (MDD) and Alcohol Use Disorders (AUDs) is frequent, causing more burden than each disorder separately. Since the dorsolateral prefrontal cortex (DLPFC) is critically involved in both mood and reward and dysfunctional in both conditions, we aimed to evaluate the effects of dTMS stimulation of bilateral DLPFC with left prevalence in patients with MDD with or without concomitant AUD. Methods: Twelve MDD patients and 11 with concomitant MDD and AUD (MDD+AUD) received 20 dTMS sessions. Clinical status was assessed through the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions severity scale (CGIs), craving through the Obsessive Compulsive Drinking Scale (OCDS) in MDD+AUD, and functioning with the Global Assessment of Functioning (GAF). Results: There were no significant differences between the two groups in sociodemographic (age, sex, years of education and duration of illness) and baseline clinical characteristics, including scores on assessment scales. Per cent drops on HDRS and CGIs scores at the end of the sessions were respectively 62.6% and 78.2% for MDD+AUD, and 55.2% and 67.1% for MDD (p<0.001). HDRS, CGIs and GAF scores remained significantly improved after the 6-month follow-up. HDRS scores dropped significantly earlier in MDD+AUD than in MDD LIMITATIONS: The small sample size and factors inherent to site and background treatment may have affected results. Conclusions: High frequency bilateral DLPFC dTMS with left preference was well tolerated and effective in patients with MDD, with or without AUD. The antidepressant effect of dTMS is not affected by alcohol abuse in patients with depressive episodes. The potential use of dTMS for mood modulation as an adjunct to treatment in patients with a depressive episode, with or without alcohol abuse, deserves further investigation.
    Journal of Affective Disorders 11/2014; 174. DOI:10.1016/j.jad.2014.11.015 · 3.38 Impact Factor
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