Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: A pilot study of acute safety and efficacy

Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston 29425, USA.
Bipolar Disorders (Impact Factor: 4.97). 02/2003; 5(1):40-7. DOI: 10.1034/j.1399-5618.2003.00011.x
Source: PubMed


Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD).
We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly.
Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (>50% decline in HRSD or HRSD <10 - 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks (t = -0.22, p = 0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment (t = 1.58, p = 0.13). The motor threshold did not significantly change after 2 weeks of active treatment (t = 1.11, p = 0.28).
Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression.

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    • "The recent sham-controlled trials report controversial results (Kaptsan, Yaroslavsky, Applebaum, Belmaker, and Grisaru, 2003; Praharaj, Ram, and Arora, 2009). As for the clinical trials for bipolar depression, the efficacy of rTMS has been reported to be effective (Dolberg, Dannon, Schreiber, and Grunhaus, 2002; Nahas, Kozel, Li, Anderson, and George, 2003), similar to the result shown in those for unipolar depression. The evidence for the maintenance effect or prophylactic effect of rTMS is not sufficient, but Li et al. reported that weekly rTMS can be an adjunctive maintenance treatment in some bipolar depression patients (Li, Nahas, Anderson, Kozel, and George, 2004), and Dell'osso et al. reported the patents with bipolar depression maintained a remission up to one year after acute rTMS treatment (Dell'osso, D'Urso, Castellano, Ciabatti, and Altamura, 2011). "
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    DESCRIPTION: Transcranial magnetic stimulation (TMS) was introduced as a novel method of brain stimulation in 1985, and now it is widely used in research of cortical excitability, neuronal connectivity and plasticity, and also is applied to the treatment of various neurological and psychiatric conditions. This review is written with the purpose of introducing the brief conspectus and area of therapeutic application of TMS. The techniques, equipment and treatment modalities of TMS are continuously developing, and its area of therapeutic application is being extended. For determining the form of the optimal therapeutic application of TMS in various clinical conditions, more data from controlled studies should be obtained.
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    • "affective disorders ( 1 Hz , 15 days , 420 daily pulses ) and were associated with clinical response ( Pallanti et al . , 2012 ) . The majority of the studies ( 10 in total : 8 DLPFC ; 2 TC ) did not reveal any changes in RMT independent of the treatment frequency , number of daily pulses , and treatment days , e . g . , ( Dolberg et al . , 2002 ; Nahas et al . , 2003 ; Ahmed et al . , 2012 ) . Within these 10 studies , sub - group - dependent changes of RMT ( Pretalli et al . , 2012 ) and sub - groups with low and high variability in RMT ( Zarkowski et al . , 2009 ) were reported . For cerebellar stimulation , three studies investigated the effects of different TMS protocols ( rTMS and TBS ) on RMT "
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    ABSTRACT: Motor cortex excitability can be measured by single-and paired-pulse transcranial magnetic stimulation (TMS). Repetitive transcranial magnetic stimulation (rTMS) can induce neuroplastic effects in stimulated and in functionally connected cortical regions. Due to its ability to non-invasively modulate cortical activity, rTMS has been investigated for the treatment of various neurological and psychiatric disorders. However, such studies revealed a high variability of both clinical and neuronal effects induced by rTMS. In order to better elucidate this meta-plasticity, rTMS-induced changes in motor cortex excitability have been monitored in various studies in a pre-post stimulation design. Here, we give a literature review of studies investigating motor cortex excitability changes as a neuronal marker for rTMS effects over non-motor cortical areas. A systematic literature review in April 2014 resulted in 29 articles in which motor cortex excitability was assessed before and after rTMS over non-motor areas. The majority of the studies focused on the stimulation of one of three separate cortical areas: the prefrontal area (17 studies), the cerebellum (8 studies), or the temporal cortex (3 studies). One study assessed the effects of multi-site rTMS. Most studies investigated healthy controls but some also stimulated patients with neuropsychiatric conditions (e.g., affective disorders, tinnitus). Methods and findings of the identified studies were highly variable showing no clear systematic pattern of interaction of non-motor rTMS with measures of motor cortex excitability. Based on the available literature, the measurement of motor cortex excitability changes before and after non-motor rTMS has only limited value in the investigation of rTMS related meta-plasticity as a neuronal state or as a trait marker for neuropsychiatric diseases. Our results do not suggest that there are systematic alterations of cortical excitability changes during rTMS treatment, which calls into question the practice of readjusting the stimulation intensity according to the motor threshold over the course of the treatment.
    Frontiers in Human Neuroscience 07/2015; 9. DOI:10.3389/fnhum.2015.00416 · 2.99 Impact Factor
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    • "The use of 5 Hz stimulation, compared to 10 Hz should also be noted. 5 Hz rTMS has been safely used in bipolar patients taking mood stabilizers 3, 5, 11. Lower frequency rTMS has been associated with an accelerated antidepressant effect as an add-on treatment to medication in MDD subjects compared to sham 2. Nonetheless, singular cases of rTMS-induced hypomania in bipolar patients have been reported for both 5 and 10 Hz parameters 6, 7. "
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    ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a comparatively novel option for the treatment of major depressive disorder (MDD) and other psychiatric illnesses. Previous research has shown rTMS to be safe and without significant side effects compared to pharmacologic options. However, rare cases of rTMS-induced mania have been reported. This case report describes such an affective switch in a 52 year old female veteran with treatment-resistant MDD and a history of electroconvulsive therapy (ECT)-induced mania. Six treatments of rTMS were administered at 5 Hz for a total of 3000 pulses per day, when the patient began to display multiple hypomanic symptoms. These symptoms decreased after the termination of treatment and abated within a couple of days. In conclusion, caution should be used when administering rTMS to patients with a history of ECT-induced mania.
    F1000 Research 12/2013; 2:284. DOI:10.12688/f1000research.2-284.v1
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