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[Effectiveness of ketamine in depressed patients resistant to ECT or rTMS therapy]. Gosek Paweł,Chojnacka Magdalena,Bieńkowski Przemysław,Swiecicki Łukasz Psychiatria polska OBJECTIVES:In the last decade several authors described a robust and clinically relevant alleviation of depressive symptoms after infusions of the uncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist - ketamine. In the majority of published reports ketamine was administrated to patients with depression resistant to pharmacotherapy, but not to ECT. We present a series of 5 subjects suffering from multimodal treatment-resistant depression (including ECT or rTMS and various medications) treated with intravenous infusions of ketamine in a subanesthetic dose of 0.5 mg/kg in the naturalistic setting. To the best of our knowledge it is the first report on ketamine infusion in patient resistant to antidepressants and r TMS METHODS:Two subjects have been diagnosed with MDD, one with BD, two with severe depressive episode. The efficacy and possible adverse events were monitored using psychometric scales. Basic life parameters and ECG were observed. RESULTS:Ketamine's infusions showed transient antidepressant efficacy. Improvement rate in our group was significant lower than in previously reported. Ketamine was generally well tolerated. We noted transient BP variations and appearance of mild and transient dissociative symptoms. Low early response rate may be correlated with resistance to previous multimodal treatment, high rate of somatization and anxiety comorbidity or heterogeneity of our group. CONCLUSIONS:Our findings do not support the use of ketamine infusions as the monotherapy in the subgroup of patients with multimodal treatment resistant depression.
Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Cole Eleanor J,Stimpson Katy H,Bentzley Brandon S,Gulser Merve,Cherian Kirsten,Tischler Claudia,Nejad Romina,Pankow Heather,Choi Elizabeth,Aaron Haley,Espil Flint M,Pannu Jaspreet,Xiao Xiaoqian,Duvio Dalton,Solvason Hugh B,Hawkins Jessica,Guerra Austin,Jo Booil,Raj Kristin S,Phillips Angela L,Barmak Fahim,Bishop James H,Coetzee John P,DeBattista Charles,Keller Jennifer,Schatzberg Alan F,Sudheimer Keith D,Williams Nolan R The American journal of psychiatry OBJECTIVE:New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression. METHODS:Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. RESULTS:One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects. CONCLUSIONS:SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study. 10.1176/appi.ajp.2019.19070720
Sham Treatment Is as Effective for Treatment-Resistant Depression as Repetitive Transcranial Magnetic Stimulation. Chow Zad Rafi JAMA psychiatry 10.1001/jamapsychiatry.2018.2755
Repetitive transcranial magnetic stimulation for depression. Chekroud Adam Mourad,Cristea Ioana Alina Lancet (London, England) 10.1016/S0140-6736(18)32760-0
Dorsomedial prefrontal cortex repetitive transcranial magnetic stimulation for treatment-refractory major depressive disorder: A three-arm, blinded, randomized controlled trial. Dunlop Katharine,Sheen Jack,Schulze Laura,Fettes Peter,Mansouri Farrokh,Feffer Kfir,Blumberger Daniel M,Daskalakis Zafiris J,Kennedy Sidney H,Giacobbe Peter,Woodside Blake,Downar Jonathan Brain stimulation BACKGROUND:Dorsomedial prefrontal cortex (DMPFC) repetitive transcranial magnetic stimulation (rTMS) is a novel intervention for treatment-refractory depression (TRD). To date, many open-label case series and one randomized controlled trial of modest sample size have provided preliminary evidence that DMPFC-rTMS is an effective treatment for TRD. Here, we report the results of a large, double-blinded, sham-controlled trial of DMPFC-rTMS for TRD. OBJECTIVE:The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions. METHODS:120 TRD patients were randomized to receive 30 twice-daily sessions of either active high-frequency, active low-frequency, or sham DMPFC-rTMS using a novel bent active/sham double-cone coil. Placebo stimulation also involved the use of surface electrodes placed above the eyebrows. The 17-item Hamilton Rating Scale for Depression served as the primary outcome measure. RESULTS:Although there was a significant main effect of treatment across all arms, active DMPFC-rTMS was not superior to sham. Both participants and assessors were unable to accuracy determine whether patients received active or placebo stimulation. However, technicians' treatment arm guesses were significantly above chance. CONCLUSION:DMPFC rTMS did not result in improvement of depressive symptoms greater than sham stimulation. We cannot rule out that the sham apparatus may also have elicited an antidepressant effect via electrical trigeminal stimulation; future DMPFC-rTMS trials are therefore warranted. 10.1016/j.brs.2019.10.020
Can psychological features predict antidepressant response to rTMS? A Discovery-Replication approach. Krepel Noralie,Rush A John,Iseger Tabitha A,Sack Alexander T,Arns Martijn Psychological medicine BACKGROUND:Few studies focused on the relationship between psychological measures, major depressive disorder (MDD) and repetitive transcranial magnetic stimulation (rTMS) response. This study investigated several psychological measures as potential predictors for rTMS treatment response. Additionally, this study employed two approaches to evaluate the robustness of our findings by implementing immediate replication and full-sample exploration with strict p-thresholding. METHODS:This study is an open-label, multi-site study with a total of 196 MDD patients. The sample was subdivided in a Discovery (60% of total sample, n = 119) and Replication sample (40% of total sample, n = 77). Patients were treated with right low frequency (1 Hz) or left high frequency (10 Hz) rTMS at the dorsolateral prefrontal cortex. Clinical variables [Beck Depression Inventory (BDI), Neuroticism, Extraversion, Openness Five-Factor Inventory, and Depression, Anxiety, and Stress Scale, and BDI subscales] were obtained at baseline, post-treatment, and at follow-up. Predictors were analyzed in terms of statistical association, robustness (independent replication), as well as for their clinical relevance [positive predictive value (PPV) and negative predictive value (NPV)]. RESULTS:Univariate analyses revealed that non-responders had higher baseline anhedonia scores. Anhedonia scores at baseline correlated negatively with total BDI percentage change over time. This finding was replicated. However, anhedonia scores showed to be marginally predictive of rTMS response, and neither PPV nor NPV reached the levels of clinical relevance. CONCLUSIONS:This study suggests that non-responders to rTMS treatment have higher baseline anhedonia scores. However, anhedonia was only marginally predictive of rTMS response. Since all other psychological measures did not show predictive value, it is concluded that psychological measures cannot be used as clinically relevant predictors to rTMS response in MDD. 10.1017/S0033291718004191