The sponsor had no role in the collection, management, analysis, and interpretation of the data; and also no role in the preparation, review, or approval of the manuscript. These observations might explain why benzodiazepine users in our study presented a worse clinical outcome regardless of allocation group. Deep TMS Treatment for Bipolar Disorder. Only 10 (20%) patients, 4 in sham and 6 in active, were on ADs at baseline and needed a drug washout. Exclusion criteria included other neuropsychiatric conditions per DSM-IV criteria (such as unipolar depression, schizophrenia, substance dependence, dementias, traumatic brain injury, epilepsy, and others—although anxiety disorders as comorbidities were included, provided the primary diagnosis was bipolar disorder); severe personality disorders; presence of (hypo)manic symptoms at baseline and/or a Young Manic Rating Scale (YMRS)>12 points; rapid-cycling bipolar disorder; acute suicidal ideation; pregnancy; specific contraindications to rTMS and motor threshold (MT)>70% of maximum stimulator output assessed at the screening visit. Recruitment strategies included referrals from physicians, patients from academic mood disorders clinics and advertisement through social media and local newspapers. All patients presented treatment-resistant depression (TRD). Epub 2020 Mar 27. The doctor performing the treatment will determine the amount of magnetic energy needed during the first treatment session. 2016 Apr;75:107-15. doi: 10.1016/j.jpsychires.2015.12.019. Researchers found that TMS was more effective than sham TMS … Our study lasted 8 weeks, with a 4-week follow-up period after the acute treatment phase, when patients received no extra stimulation sessions. Furthermore, no clinical episodes of TEMS were observed during the treatment. Secondary efficacy outcomes included response and remission status at week 4, depression improvement from baseline to week 8, and response and remission status at week 8. J Psychiatr Res 74: 38–44. 2021 Feb;271(1):93-100. doi: 10.1007/s00406-020-01121-2. (2021), Neuroscience & Biobehavioral Reviews Bipolar depression (BD) is a … Deng ZD, Lisanby SH, Peterchev AV (2013). TMS treatments will last about 40 minutes. CAS  See this image and copyright information in PMC. 2020 Oct 15;12(5):128-133. eCollection 2020. Neurosci Lett. ; Sheehan et al, 1998). volume 42, pages2593–2601(2017)Cite this article. Rapinesi C, Kotzalidis GD, Ferracuti S, Girardi N, Zangen A, Sani G, Raccah RN, Girardi P, Pompili M, Del Casale A; Sapienza Centre for Research on Personalised Mental Health. Google Scholar. There were 2 dropouts in the sham group (both because of consecutive missing visits) and 5 dropouts in the active group (two were drop-outs for consecutive missing visits, two because of the severity of depressive symptoms and one because of side effects such as headache and burning sensation over the scalp), which was not statistically different (p=0.21; Figure 1). Of ~280 volunteers, 268 were screened and 216 were excluded for several reasons (Figure 1). Other adverse events such as headache, neck pain, burning sensation, hearing complaints and concentration difficulties presented non-significantly different rates between groups (Supplementary Table 2). Volume DHEW Publ No ADM 76.338. Increasing evidence suggests that transcranial magnetic stimulation (TMS), already FDA-approved for major depressive disorder, may help people with treatment-resistant bipolar depression, … Deep TMS (dTMS) has been reported to be efficacious in bipolar depression, but there are no data concerning mixed states. Therefore, our results should be interpreted as preliminary and hypothesis-driven for future, pivotal trials. Williams JR (2008). A recent meta-analysis suggested that rTMS is effective in BD (McGirr et al, 2016). For a power of 90% and a two-tailed ð of 5%, we obtained a sample size of 40 patients, which was enriched to a final number of 50 participants (25 per group), considering attrition. Our primary hypothesis was that BD patients in the active group would present a statistically greater improvement in their depressive symptoms compared to those in the sham group at the end of the acute intervention phase (four weeks of treatment). While there is a growing anecdotal database supporting its use in bipolar depression … In fact, 86% of our sample was composed of patients using at least one treatment considered as a first-line therapy according to CANMAT guidelines (Yatham et al, 2013) at trial onset, with 50% of BD patients using lithium in clinically effective doses. In the present study, the placebo response was lower than 30%, which adds evidence on its internal validity. There was also a trend for greater response rates in the active (48%) vs sham (24%) groups (OR=2.92; 95% CI=0.87 to 9.78, p=0.08). Bipol Disord 15: 61–69. Please be aware that TMS is not FDA approved for the treatment of Bipolar Depression. 470904). In fact, in a recent meta-analysis (Kedzior et al, 2015) assessing the antidepressant effects of rTMS after the acute treatment phase, rTMS effects in unipolar depression were stable; although no long-lasting antidepressant effects were observed in trials that also included BD. Evid Based Ment Health 19: e16. Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L et al (2007). Pacchiarotti I, Bond DJ, Baldessarini RJ, Nolen WA, Grunze H, Licht RW et al (2013). Maintenance treatment of transcranial magnetic stimulation (TMS) for treatment-resistant depression patients responding to acute TMS treatment. We enrolled 50 adults aging from 18 to 65 years old diagnosed with bipolar disorder types I or II in an acute depressive episode. Two small randomized controlled … FOIA J Neurol Neurosurg Psychiatry 23: 56–62. Options for pharmacological treatment of refractory bipolar depression. Treatment of Bipolar Depression with Deep TMS: Results from a Double-Blind, Randomized, Parallel Group, Sham-Controlled Clinical Trial Abstract. Sienaert P, Lambrichts L, Dols A, De Fruyt J (2013). Deep TMS with the H1 coil is FDA approved for the treatment of depression in patients who have not improved by using any number of medications. Tavares, D., Myczkowski, M., Alberto, R. et al. Demographic and clinical data were collected, including age, age at onset of the first episode, marital status, occupational status, diagnosis subtype, duration of illness, medication use, and others. Castelein S, de Kort SJ, van der Moolen AE, Houtjes W, Roodbol PF, van Meijel B et al (2014). Levkovitz Y, Harel EV, Roth Y, Braw Y, Most D, Katz LN et al (2009). A negative double-blind controlled trial of sequential bilateral rTMS in the treatment of bipolar depression. In our study, we employed no maintenance schedule from weeks 4 to 8 devising that the mood stabilizers the patients were in use would sustain clinical improvement after the acute treatment phase. World J Biol Psychiatry 11: 81–109. J Affect Disord. A clinical trial of studying the feasibility of using the Deep TMS H System for treating bi-polar disorder episodes, took place at the Shalvata Mental Health Center, Hod … You are using a browser version with limited support for CSS. Out of 50 patients, 43 finished the trial. Clinical predictors associated with duration of repetitive transcranial magnetic stimulation treatment for remission in bipolar depression: a naturalistic study. Durability of the antidepressant effect of the high-frequency repetitive transcranial magnetic stimulation (rTMS) In the absence of maintenance treatment in major depression: a systematic review and meta-analysis of 16 double-blind, randomized, sham-controlled trials. Transcranial magnetic stimulation, or TMS, is a noninvasive form of brain stimulation. Epub 2015 Dec 22. Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. The active stimulation consisted of 55 18 Hz, 2 s trains at 120% MT intensity, with a between-train interval of 20 s (1980 pulses per day or 39 600 pulses per treatment). Matsuda Y, Kito S, Igarashi Y, Shigeta M. Neuropsychobiology. World Psychiatry 15: 85–86. The presence of treatment-emergent mania switch (TEMS) was assessed according to the ISBD recommendations that consider TEMS as likely when there are 2 or more manic symptoms (eg, irritability or euphoria (racing thoughts, grandiosity, decreased need for sleep), and YMRS>12; Tohen et al, 2009). Here TRD was conceptualized as the failure to achieve remission with ⩾2 interventions (Parker and Graham, 2016) approved as first (lithium, lithium+divalproex, quetiapine, or lamotrigine), second (divalproex, lithium+lamotrigine, or divalproex+lamotrigine), or third line (carbamazepine, olanzapine, lithium+carbamazepine, and quetiapine+lamotrigine) therapies for BD according to CANMAT guidelines ((Yatham et al, 2013). Careers. Allocation concealment consisted of sequentially numbered cards, which determined whether the TMS machine would produce real or sham stimulation. Good clinical practice and the maintenance of ethical standards in medical research: advice for junior researchers working in mental health care. In open-label studies, the response rate for bipolar … PubMed  To reduce local side effects and increase tolerability, rTMS pivotal studies (eg, (George et al, 2010)) allow to progressively up-titrate stimulation intensity during or over several sessions. Would you like email updates of new search results? TMS devices operate completely outside of the body and affect central nervous system activity by applying powerful magnetic fields to specific areas of the brain that we know are involved in depression. PubMed  Holtzman JN, Lolich M, Ketter TA, Vazquez GH (2015). Long-term deep-TMS does not negatively affect cognitive functions in stroke and spinal cord injury patients with central neuropathic pain. The main eligibility criterion was the presence of a depressive episode of at least moderate intensity, corresponding to a Hamilton Depression Rating Scale (17-items; HDRS-17)>17 (Hamilton, 1960). Depress Anxiety 29: 587–596. Both differences were not statistically significant (t=0.85, p=0.4; t=0.8, p=0.43 for raters and patients, respectively). After that, pairwise comparisons were performed at each time point (contrast command in Stata). Cohen RB, Brunoni AR, Boggio PS, Fregni F (2010). A recent study (Iovieno et al, 2016) discussed that placebo responses higher than 30% in bipolar disorder placebo-controlled trials might harm trial performance. Front Neurol 6: 16. Complexity of illness and adjunctive benzodiazepine use in outpatients with bipolar I or II disorder: results from the Bipolar CHOICE study. Patients who presented >70% of MT of maximum stimulator output at baseline were not included. Rapinesi C, Bersani FS, Kotzalidis GD, Imperatori C, Del Casale A, Di Pietro S et al (2015). With TMS, a large electromagnetic coil is placed on a person’s forehead and short pulses are directed into an area of the brain believed to control moods. Correspondence to Google Scholar. Tortella G, Sampaio-Junior B, Moreno ML, Moffa AH, da Silva AF, Lafer B, Lotufo PA, Gattaz W, Borrione L, Machado-Vieira R, Goerigk S, Benseñor IM, Brunoni AR. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation therapy with established efficacy and acceptability for unipolar depression (George et al, 2010). The present research protocol will evaluate clinical-cognitive and safety effects of H1-Coil Deep Brain Transcranial Magnetic Stimulation over prefrontal cortex in subjects with bipolar depression… All participants signed informed consent form. This criterion was employed because higher applied intensities produce more adverse events such as head and local pain. Transcranial Magnetic Stimulation (TMS) is an increasingly accepted neurostimulation- based treatment for major depressive disorder. Fitzgerald PB, Hoy KE, Elliot D, McQueen S, Wambeek LE, Daskalakis ZJ (2016). Tijdschr Psychiatr 56: 533–538. 20911-5), the Brain and Behavior research foundation (Grant Number 20493) and a National Council for Scientific and Technological Development Grant (CNPq, Grant no. Hamilton M (1960). J Ner Ment Dis 205: 188–191. Accessibility Also, this meta-analysis suggested that low-frequency rTMS over the right DLPFC might be more effective than high-frequency over the left DLPFC. No TEMS episodes were observed. Our findings showing promising results for dTMS in bipolar depression stimulate further non-inferiority trials comparing the efficacy of this technique with standard rTMS approaches, which, although are costly and require large sample sizes, are necessary to assess which non-pharmacological therapy produces greater depression improvement. Zimmerman M (2016). 2019 Jul;17(3):232-237. doi: 10.1176/appi.focus.20190009. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for unipolar depression. A rating scale for depression. Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. The median duration of the current depressive episode was 6 months (IQR 3–12). Although hypomania and mania episodes characterize the disorder, depressive episodes in fact exceed them in duration and frequency (Holtzman et al, 2015; Perich et al, 2016; Zimmerman, 2016). Evidence highlights that TMS can reduce the symptoms of depression. The primary efficacy outcome was defined as the change in HDRS-17 from baseline to week 4. Article  Forty-three patients (86%) were using at least one treatment considered a first-line therapy per CANMAT guidelines (Table 1). The treatment performs magnetic … We performed the first randomized, sham-controlled clinical assessing the efficacy, safety and tolerability of the H1-coil TMS for the treatment of resistant bipolar depression. Conceivably, bipolar depressed patients might also profit from a longer treatment regimen and/or a maintenance treatment after the acute treatment phase when receiving dTMS. Analyses were performed in Stata 14 (Statacorp, College Station, TX, USA). Secondary outcomes were changes from baseline to the end of the follow-up phase (week 8), and response and remission rates. Personalized TMS For Bipolar … Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex in depressive episodes of patients with major depressive disorder, bipolar disorder I, and major depressive with alcohol use disorders. Maintenance deep transcranial magnetic stimulation sessions are associated with reduced depressive relapses in patients with unipolar or bipolar depression. TMS is typically used when other depression treatments haven't been effective.This treatment for depression involves delivering repetitive magnetic pulses, so it's called repetitive TMS or rTMS. Neurostimulation treatments. The present randomized, sham-controlled trial showed that deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy. Clinical characteristics associated with treatment-resistant bipolar disorder. Therefore, this coil could stimulate deeper dorsolateral and ventrolateral prefrontal areas that also projects into other brain areas that present impaired functioning in depression (Luborzewski et al, 2007). The mean percentage of missing visits was 4.5%, being 7.1% in the sham group and 1.7% in the (p=0.044). Patients who presented two consecutive missing visits were considered washouts. Studies have demonstrated that TMS is an effective and safe intervention for individuals with bipolar depression, as long as parameters are being watched closely. Roth Y, Amir A, Levkovitz Y, Zangen A (2007). Eur Psychiatry 28: 30–39. Li CT, Bai YM, Huang YL, Chen YS, Chen TJ, Cheng JY et al (2012). To verify blinding integrity, we asked, at week 8, for patients and raters to guess whether the allocation group was active on a 0–100 scale; guessing scores were compared using a t-test. We performed an intention-to-treat (ITT) analysis using the last observation carried forward (LOCF) approach. Our primary hypothesis was that the interaction of time with group would be significant, with active dTMS being superior to sham at week 4. Tondo L, Vazquez GH, Baldessarini RJ (2014). Moreover, patients in the active group presented significantly greater improvement in the GAF and CGI scores. (2021), Current Behavioral Neuroscience Reports Selingardi PML, de Lima Rodrigues AL, da Silva VA, Fernandes DTRM, Rosí J Jr, Marcolin MA, Yeng LT, Brunoni AR, Teixeira MJ, Galhardoni R, de Andrade DC. However, our findings are not generalizable to patients presenting MT>70% at baseline, an issue that should be investigated in future studies. There was also a trend for greater response rates in the active (48%) vs sham (24%) groups (OR=2.92; 95% CI=0.87 to 9.78, p=0.08). 42, 2593–2601 (2017). To obtain Psychopharmacology and Experimental Therapeutics for Bipolar Depression. MTs were reassessed at the first day of treatment and then every week. Deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy. Major depression as a component of bipolar … Middleton H, Shaw I, Hull S, Feder G (2005). Therefore, we conducted a randomized, sham-controlled clinical trial to evaluate the effectiveness and tolerability of deep-TMS as an add-on therapy to pharmacological treatment of resistant bipolar depressed patients. These effects were independent of anxiety levels or comorbidity. No interactions between groups with any predictor variable, including type of bipolar disorder and number of failed effective treatments in the present episode, were found (Supplementary Table 3). Hamilton M (1959). The primary outcome was changes in the 17-item Hamilton Depression Rating Scale (HDRS-17) from baseline to endpoint (week 4). In this study, we evaluated the cognitive effects of H1-coil (deep) transcranial magnetic stimulation (TMS) in patients with treatment-resistant bipolar depression. Chang J, Chu Y, Ren Y, Li C, Wang Y, Chu XP. Deep transcranial magnetic stimulation over the prefrontal cortex: evaluation of antidepressant and cognitive effects in depressive patients. Patients have also seen beneficial results for … Secondary outcomes were changes from baseline to the end of the follow-up phase (week 8), and response and remission rates. Can J Psychiatry 61: 561–575. However, only preliminary studies have addressed rTMS efficacy in BD. Goodwin GM, Haddad PM, Ferrier IN, Aronson JK, Barnes T, Cipriani A et al (2016). Unlike ECT, TMS does not require the use of anesthesia and pers… In fact, large, pragmatic clinical trials in bipolar disorder showed that benzodiazepine use in patients with bipolar depression seems to be a marker for a more severe course of illness, presents a higher risk of recurrence and is associated with greater illness complexity and higher burden of disease (Bobo et al, 2015; Perlis et al, 2010). Finally, we employed no neuronavigated methods for target localization. The degree of confidence of active group allocation was, for raters, 52.17 (29.53) and 60 (31.46) in patients that received sham and active stimulation, respectively; while for patients it was 45.65 (30.46) and 53.57 (35.57), respectively. All clinical assessments were performed by a certified psychiatrist (DFT) and a certified psychologist (MLM) who are trained in the application of the structured questionnaires and interviews used in the present study. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for … H-coil repetitive transcranial magnetic stimulation for the treatment of bipolar depression: an add-on, safety and feasibilitystudy. Please enable it to take advantage of the complete set of features! Comparisons regarding response and remission at week 8 were not statistically significant (Table 3). There were 2 and 5 dropouts in the sham and active groups, respectively. Comparisons at week 8 and regarding HAM-A were not statistically significant (Supplementary Table 1). No TEMS episodes were observed. Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. and JavaScript. Before the screening interview, potential participants had their MT (the lowest stimulation intensity necessary to evoke a motor potential with at least 50 μV amplitude in 50% of attempts) assessed to determine eligibility. Finally, dTMS was similarly effective for both bipolar I and bipolar II patients. Clinical and demographic variables were compared between groups using t-tests, Mann–Whitney test, χ2 tests, or the Fisher’s exact test and described using mean (standard deviation), median (interquartile range), or number of events (frequency) according to the type of the variable and its normality (assessed using the Shapiro–Wilk test). 2019 Dec 10;19(1):319. doi: 10.1186/s12883-019-1531-z. Importantly, dTMS was not only effective in treating depressive symptoms, but also in improving global functioning. Google Scholar. At week 4, patients in the active group presented significant greater improvement compared to sham in the GAF (percentage of improvement 65.37% (53.46) vs 34.07% (48.62), p=0.03, respectively) and CGI scores (36.47% (22.87) vs 19.2% (30.96), p=0.03, respectively). Frequency of TEMS and adverse events were compared among groups using Fisher’s exact test or the χ2 test. It is the safest treatment with the least side effects for … Scalp pain rates were higher in the active (20%) vs sham (0%) groups (p=0.05). In the last 3 years, ZJD received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc and Magventure Inc. ZJD has also served on the advisory board for Sunovion, Hoffmann-La Roche Limited and Merck and received speaker support from Eli Lilly. Missing data were considered to be at random. Nonetheless, negative results were also found in recent trials (Fitzgerald et al, 2016). This work was primarily sponsored by Brainsway, which provided the dTMS devices and financial support. A sham coil is also included in the same helmet. This site needs JavaScript to work properly. J Psychiatr Res 41: 606–615. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. As our study used a low sample size, we adopted the maximum MT eligibility criterion aiming to increase patients’ adherence and the trial’s internal validity. Results were similar in the PP analyses (Table 2). The groups were similar in all main clinical and demographic characteristics at baseline. However, this approach was associated with lower dTMS efficacy in the pivotal dTMS depression trial (Levkovitz et al, 2015), possibly because sessions at intensities <120%MT are less effective (Levkovitz et al, 2009). Active dTMS was superior to sham at end point (difference favoring dTMS=4.88; 95% CI 0.43 to 9.32, p=0.03) but not at follow-up. J Clin Psychopharmacol 35: 68–74. World J Biol Psychiatry 12: 119–126. Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ et al (2010). Missing visits were replaced at the end of the acute stimulation phase; therefore, all patients received 20 dTMS sessions. Active dTMS was superior to sham at end point (difference favoring dTMS=4.88; 95% CI 0.43 to 9.32, p=0.03) but not at follow-up. In other words, both raters and patients were unable to identify the allocation group beyond chance. Parker GB, Graham RK (2017). Bersani FS, Minichino A, Enticott PG, Mazzarini L, Khan N, Antonacci G et al (2013). US Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs. Out of 50 patients, 43 finished the trial. Milev RV, Giacobbe P, Kennedy SH, Blumberger DM, Daskalakis ZJ, Downar J et al (2016). The sample was composed mainly of women (70%), with a mean age of 42.34 (SD=10.54) years. TMS is a procedure that creates magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression. Furthermore, in the dTMS unipolar depression trial (Levkovitz et al, 2015), 20 stimulations sessions were followed by two sessions per week for 12 weeks. Deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy. Patients received 20 sessions of active or sham dTMS over the left dorsolateral prefrontal cortex (H1-coil, 55 18 Hz 2 s 120% MT trains). In fact, a large randomized controlled trial showed that dTMS was effective and well-tolerated in depression treatment, with response and remission rates of, respectively, 38.4 and 32.6% (Levkovitz et al, 2015). Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. National Library of Medicine Br J Psychiatry 133: 429–435. Bobo WV, Reilly-Harrington NA, Ketter TA, Brody BD, Kinrys G, Kemp DE et al (2015). The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. No clinical episodes of TEMS were observed.