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Ziad Nahas,
Baron Short,
Carol Burns,
Melanie Archer,
Matthew Schmidt,
Joan Prudic,
Mitchell S Nobler,
D P Devanand,
Linda Fitzsimons, Sarah H Lisanby,
Nancy Payne,
Tarique Perera,
Mark S George,
Harold A Sackeim
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ABSTRACT: BACKGROUND: Electroconvulsive therapy (ECT) remains the most effective acute treatment for severe major depression, but with significant risk of adverse cognitive effects. Unidirectional electrical stimulation with a novel electrode placement and geometry (Focal Electrically Administered Seizure Therapy (FEAST)) has been proposed as a means to initiate seizures in prefrontal cortex prior to secondary generalization. As such, it may have fewer cognitive side effects than traditional ECT. We report on its first human clinical application. METHOD: Seventeen unmedicated depressed adults (5 men; 3 bipolar disorder; age 53 ± 16 years) were recruited after being referred for ECT. Open-label FEAST was administered with a modified spECTrum 5000Q device and a traditional ECT dosing regimen until patients clinically responded. Clinical and cognitive assessments were obtained at baseline, and end of course. Time to orientation recovery, a predictor of long-term amnestic effects, was assessed at each treatment. Nonresponders to FEAST were transitioned to conventional ECT. RESULTS: One patient withdrew from the study after a single titration session. After the course of FEAST (median 10 sessions), there was a 46.1 ± 35.5% improvement in Hamilton Rating Scale for Depression (HRSD24) scores compared to baseline (33.1 ± 6.8, 16.8 ± 10.9; P < 0.0001). Eight of 16 patients met response criteria (50% decrease in HRSD24) and 5/16 met remission criteria (HRSD24 ≤ 10). Patients achieved full re-orientation (4 of 5 items) in 5.5 ± 6.4 min (median = 3.6), timed from when their eyes first opened after treatment. CONCLUSION: In this feasibility study, FEAST produced clinically meaningful antidepressant improvement, with relatively short time to reorientation. Our preliminary work first in primates and now depressed adults demonstrates that FEAST is feasible, safe, well-tolerated and, if efficacy can be optimized, has potential to replace traditional ECT.
Brain Stimulation 03/2013; · 3.76 Impact Factor
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ABSTRACT: Transcranial magnetic stimulation (TMS) can be used to probe cortical function and treat neuropsychiatric illnesses. TMS has demonstrated neuroplastic effects akin to long-term potentiation and long-term depression, and therapeutic applications are in development for post-stroke recovery, Alzheimer's disease, and depression in seniors. Here, we discuss two new directions of TMS research relevant to cerebral aging and cognition. First, we introduce a paradigm for enhancing cognitive reserve, based on our research in sleep deprivation. Second, we discuss the use of magnetic seizure therapy (MST) to spare cognitive functions relative to conventional electroconvulsive therapy, and as a means of providing a more potent antidepressant treatment when subconvulsive TMS has shown modest efficacy in seniors. Whether in the enhancement of cognition as a treatment goal, or in the reduction of amnesia as a side effect, these approaches to the use of TMS and MST merit further exploration regarding their clinical potential.
Dialogues in clinical neuroscience. 03/2013; 15(1):87-98.
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ABSTRACT: OBJECTIVE: To demonstrate the use of a novel controllable pulse parameter TMS (cTMS) device to characterize human corticospinal tract physiology. METHODS: Motor threshold and input-output (IO) curve of right first dorsal interosseus were determined in 26 and 12 healthy volunteers, respectively, at pulse widths of 30, 60, and 120μs using a custom-built cTMS device. Strength-duration curve rheobase and time constant were estimated from the motor thresholds. IO slope was estimated from sigmoid functions fitted to the IO data. RESULTS: All procedures were well tolerated with no seizures or other serious adverse events. Increasing pulse width decreased the motor threshold and increased the pulse energy and IO slope. The average strength-duration curve time constant is estimated to be 196μs, 95% CI [181μs, 210μs]. IO slope is inversely correlated with motor threshold both across and within pulse width. A simple quantitative model explains these dependencies. CONCLUSIONS: Our strength-duration time constant estimate compares well to published values and may be more accurate given increased sample size and enhanced methodology. Multiplying the IO slope by the motor threshold may provide a sensitive measure of individual differences in corticospinal tract physiology. SIGNIFICANCE: Pulse parameter control offered by cTMS provides enhanced flexibility that can contribute novel insights in TMS studies.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 02/2013; · 3.12 Impact Factor
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ABSTRACT: Electroconvulsive therapy (ECT) is a safe and highly effective treatment for management of acute episodes of a variety of serious mental disorders, particularly for major depressive episodes that are resistant to multiple interventions with treatment alternatives. As such, the National Network of Depression Centers (NNDC), a consortium of major academic centers with interest and expertise in this area, believes there is an important public health need for ECT to remain available for clinical use. As with all medical devices, ECT is regulated by the US Food and Drug Administration (FDA), which is presently involved in formulating a proposed rule as to how such devices should be classified. Since such classification may have substantial effects on the availability of ECT to patients for whom it is clinically indicated, the NNDC has reviewed the information provided by the FDA to its Advisory Panel, as well as the subsequent deliberations of the Panel itself at a January 2011 public hearing. This review indicates that the FDA may have substantially underestimated the efficacy of ECT as a means to produce large clinical improvements for individuals suffering from severe major depressive disorders and that such an underestimate likely affected the Panel's willingness to recommend reclassification of ECT devices to a less restrictive category. In addition, the NNDC's review generates support for a variety of methods by which the safety of ECT can be ensured, which is an essential requirement for such reclassification.
The Journal of Clinical Psychiatry 01/2013; 74(1):38-42. · 5.80 Impact Factor
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ABSTRACT: BACKGROUND: In an open-label trial low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex (DLPFC) significantly improved symptoms of panic disorder and major depression. Here we present data of a randomized double-blind study. METHODS: Twenty-five patients were assigned 4 weeks of active or sham rTMS to the right DLPFC. rTMS parameters consisted of 1800 stimuli/day, 1-Hz, at 110% of resting motor threshold. Response was defined as a ≥40% decrease on the panic disorder severity scale and a ≥50% decrease on the Hamilton depression rating scale. At the end of the randomized phase, patients were offered the option of receiving open-label rTMS for an additional 4 weeks. RESULTS: Repeated-measures ANOVA revealed significantly better improvement in panic symptoms with active compared with sham rTMS, but no significant difference in depression. At 4 weeks, response rate for panic disorder was 50% with active rTMS and 8% with sham. After 8 weeks of active rTMS, response rate was 67% for panic and 50% for depressive symptoms. Repeated-measure ANOVA showed significant improvements in panic disorder, major depression, clinical global impression, and social adjustment. Clinical improvement was sustained at 6-month follow-up. LIMITATIONS: Limitation of this study is the relatively small sample size. CONCLUSIONS: Although 4 weeks of rTMS was sufficient to produce a significant effect in panic symptoms, a longer course of treatment resulted in better outcomes for both panic disorder and major depression. These data suggest that inhibitory rTMS to the right DLPFC affects symptoms expression in comorbid anxiety and depression. ClinicalTrials.gov Identifier: NCT00521352.
Journal of affective disorders 08/2012; · 3.76 Impact Factor
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Annals of the New York Academy of Sciences 08/2012; 1265:vii-x. · 3.15 Impact Factor
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ABSTRACT: This study investigates the stimulation strength and focality of electroconvulsive therapy (ECT) with individualized current amplitude in a nonhuman primate (NHP) model. We generated an anatomically realistic finite element model of a NHP head incorporating tissue heterogeneity and white matter conductivity anisotropy based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. The electric field spatial distributions of three conventional ECT electrode placements (bilateral, bifrontal, and right unilateral) and an experimental frontomedial electrode configuration were simulated. We calibrated the electric field maps relative to an empirical neural activation threshold and evaluated the stimulation strength and focality of the various ECT electrode configurations with individualized current amplitudes corresponding to the motor threshold and seizure threshold assessed in the anesthetized NHP. Understanding the stimulation strength and focality of various forms of ECT could provide insight into the mechanisms of therapeutic seizure induction, and could provide support for the clinical investigation of ECT with individualized current amplitude as an intervention with potentially improved risk/benefit ratio.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2012; 2012:6430-3.
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ABSTRACT: Research on deep brain stimulation (DBS) for treatment-resistant depression appears promising, but concerns have been raised about the decisional capacity of severely depressed patients and their potential misconceptions about the research. We assessed 31 DBS research participants with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), a well-validated capacity measure, and with a scale to measure therapeutic misconception, which occurs when subjects do not recognize key differences between treatment and clinical research. Correlations with baseline depressive symptoms were explored. Subjects' performance on the MacCAT-CR was excellent, but therapeutic misconception was still apparent. A trend toward significance was found in the correlation between baseline depression ratings and total therapeutic misconception score. Responses to open-ended prompts revealed both reassuring and concerning statements related to expectations of risk, benefit, and individualization. Even severely depressed patients did not manifest impairments in their capacity to consent to DBS research. Therapeutic misconception, however, remained prevalent.
Annals of the New York Academy of Sciences 07/2012; 1265:69-79. · 3.15 Impact Factor
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ABSTRACT: A few studies have examined the durability of transcranial magnetic stimulation (TMS) antidepressant benefit once patients remitted. This study examined the long-term durability of clinical benefit from TMS using a protocol-specified TMS taper and either continuation pharmacotherapy or naturalistic follow-up.
Patients were remitters from an acute double-blind sham-controlled trial of TMS (n = 18), or from an open-label extension in patients who did not respond to the acute trial (n = 43). Long-term durability of TMS acute effect was examined in remitters over a 12-week follow-up. Relapse, defined as 24-item Hamilton Depression Rating Scale (HDRS-24) ≥20, was the primary outcome.
Of 61 remitters in the acute trial, five entered naturalistic follow-up and 50 entered the TMS taper. Thirty-two patients completed TMS taper and 1-, 2-, and 3-month follow-up. At 3-month visit, 29 of 50 (58%) were classified as in remission (HDRS-24 ≤10), two of 50 (4%) as partial responders (30%≤ HDRS-24 reduction <50% from baseline), and one of 50 (2%) met criteria for relapse. During the entire 3-month follow-up, five of the 37 patients relapsed (relapse rate = 13.5%), but four of them regained remission by the end of the study. The average time to relapse in these five patients was 7.2 ± 3.3 weeks. Patients who relapsed had higher depression scores at 1 month.
While one third of the sample was lost to follow-up, our results demonstrate that most patients contributing to observations experienced persistence of benefit from TMS followed by pharmacotherapy or no medication. Longer follow-up and more rigorous studies are needed to explore the true long-term durability of remission produced by TMS.
Depression and Anxiety 06/2012; 29(10):883-90. · 4.18 Impact Factor
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ABSTRACT: BACKGROUND: Various transcranial magnetic stimulation (TMS) coil designs are available or have been proposed. However, key coil characteristics such as electric field focality and attenuation in depth have not been adequately compared. Knowledge of the coil focality and depth characteristics can help TMS researchers and clinicians with coil selection and interpretation of TMS studies. OBJECTIVE: To quantify the electric field focality and depth of penetration of various TMS coils. METHODS: The electric field distributions induced by 50 TMS coils were simulated in a spherical human head model using the finite element method. For each coil design, we quantified the electric field penetration by the half-value depth, d(1/2), and focality by the tangential spread, S(1/2), defined as the half-value volume (V(1/2)) divided by the half-value depth, S(1/2) = V(1/2)/d(1/2). RESULTS: The 50 TMS coils exhibit a wide range of electric field focality and depth, but all followed a depth-focality tradeoff: coils with larger half-value depth cannot be as focal as more superficial coils. The ranges of achievable d(1/2) are similar between coils producing circular and figure-8 electric field patterns, ranging 1.0-3.5 cm and 0.9-3.4 cm, respectively. However, figure-8 field coils are more focal, having S(1/2) as low as 5 cm(2) compared to 34 cm(2) for circular field coils. CONCLUSIONS: For any coil design, the ability to directly stimulate deeper brain structures is obtained at the expense of inducing wider electrical field spread. Novel coil designs should be benchmarked against comparison coils with consistent metrics such as d(1/2) and S(1/2).
Brain Stimulation 03/2012; · 3.76 Impact Factor
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Kevin A Johnson,
Mirza Baig,
Dave Ramsey, Sarah H Lisanby,
David Avery,
William M McDonald,
Xingbao Li,
Elisabeth R Bernhardt,
David R Haynor,
Paul E Holtzheimer,
Harold A Sackeim,
Mark S George,
Ziad Nahas
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ABSTRACT: BACKGROUND: Motor cortex localization and motor threshold determination often guide Transcranial Magnetic Stimulation (TMS) placement and intensity settings for non-motor brain stimulation. However, anatomic variability results in variability of placement and effective intensity. OBJECTIVE: Post-study analysis of the OPT-TMS Study reviewed both the final positioning and the effective intensity of stimulation (accounting for relative prefrontal scalp-cortex distances). METHODS: We acquired MRI scans of 185 patients in a multi-site trial of left prefrontal TMS for depression. Scans had marked motor sites (localized with TMS) and marked prefrontal sites (5 cm anterior of motor cortex by the "5 cm rule"). Based on a visual determination made before the first treatment, TMS therapy occurred either at the 5 cm location or was adjusted 1 cm forward. Stimulation intensity was 120% of resting motor threshold. RESULTS: The "5 cm rule" would have placed stimulation in premotor cortex for 9% of patients, which was reduced to 4% with adjustments. We did not find a statistically significant effect of positioning on remission, but no patients with premotor stimulation achieved remission (0/7). Effective stimulation ranged from 93 to 156% of motor threshold, and no seizures were induced across this range. Patients experienced remission with effective stimulation intensity ranging from 93 to 146% of motor threshold, and we did not find a significant effect of effective intensity on remission. CONCLUSIONS: Our data indicates that individualized positioning methods are useful to reduce variability in placement. Stimulation at 120% of motor threshold, unadjusted for scalp-cortex distances, appears safe for a broad range of patients.
Brain Stimulation 03/2012; · 3.76 Impact Factor
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ABSTRACT: We present the first computational study investigating the electric field (E-field) strength generated by various electroconvulsive therapy (ECT) electrode configurations in specific brain regions of interest (ROIs) that have putative roles in the therapeutic action and/or adverse side effects of ECT. This study also characterizes the impact of the white matter (WM) conductivity anisotropy on the E-field distribution. A finite element head model incorporating tissue heterogeneity and WM anisotropic conductivity was constructed based on structural magnetic resonance imaging (MRI) and diffusion tensor MRI data. We computed the spatial E-field distributions generated by three standard ECT electrode placements including bilateral (BL), bifrontal (BF), and right unilateral (RUL) and an investigational electrode configuration for focal electrically administered seizure therapy (FEAST). The key results are that (1) the median E-field strength over the whole brain is 3.9, 1.5, 2.3, and 2.6 V/cm for the BL, BF, RUL, and FEAST electrode configurations, respectively, which coupled with the broad spread of the BL E-field suggests a biophysical basis for observations of superior efficacy of BL ECT compared to BF and RUL ECT; (2) in the hippocampi, BL ECT produces a median E-field of 4.8 V/cm that is 1.5-2.8 times stronger than that for the other electrode configurations, consistent with the more pronounced amnestic effects of BL ECT; and (3) neglecting the WM conductivity anisotropy results in E-field strength error up to 18% overall and up to 39% in specific ROIs, motivating the inclusion of the WM conductivity anisotropy in accurate head models. This computational study demonstrates how the realistic finite element head model incorporating tissue conductivity anisotropy provides quantitative insight into the biophysics of ECT, which may shed light on the differential clinical outcomes seen with various forms of ECT, and may guide the development of novel stimulation paradigms with improved risk/benefit ratio.
NeuroImage 02/2012; 59(3):2110-23. · 5.89 Impact Factor
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ABSTRACT: Self-ordered spatial working memory measures provide important information regarding underlying cognitive strategies, such as stereotypy. This strategy is based on repetitive sequential selection of a spatial pattern once a correct sequence has been identified. We previously reported that electroconvulsive shock (ECS) but not magnetic seizure therapy (MST) impaired performance on a spatial working memory task in a preclinical model. Here we tested the hypothesis that ECS disrupted stereotyped patterns in the selection of spatial stimuli. In a within-subject study design, we assessed the effects of ECS, MST, and sham on stereotypy and reaction time in a preclinical model. Stereotypy was assessed by the correlation of actual and predicted response patterns of spatial stimuli. Predicted patterns were based on performance during baseline sessions. ECS resulted in lower correlations between predicted and actual responses to spatial stimuli in two of the three subjects, and it also disrupted stereotypy. For one subject, there was change in the predictability of the spatial locus of responses between experimental conditions. For all three subjects, reaction time was significantly longer in ECS, relative to MST and sham. This is the first study to examine the effect of ECS, and to contrast the effects of ECS and MST, on spatial working memory component processes. Our preliminary findings show that ECS, but not MST decreased stereotypy and increased reaction time. This line of investigation may have significant implications in our understanding cognitive component processes of memory function and impairment.
The International Journal of Neuropsychopharmacology 01/2012; · 4.58 Impact Factor
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Lawrence S Kegeles,
Xiangling Mao,
Arielle D Stanford,
Ragy Girgis,
Najate Ojeil,
Xiaoyan Xu,
Roberto Gil,
Mark Slifstein,
Anissa Abi-Dargham, Sarah H Lisanby,
Dikoma C Shungu
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ABSTRACT: Postmortem studies have found evidence of γ-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness.
To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls.
Case-control study.
Inpatient psychiatric research unit and associated outpatient clinic.
Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking.
Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects.
The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy.
In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found.
To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with antipsychotic medication. The Glx elevations agree with prior magnetic resonance spectroscopy literature, but GABA elevations were unexpected and suggest possible involvement of classes of interneurons not found to show impairments in postmortem studies.
Archives of general psychiatry 01/2012; 69(5):449-59. · 12.26 Impact Factor
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ABSTRACT: Somatic treatments for mood disorders represent a class of interventions available either as a stand-alone option, or in combination with psychopharmacology and/or psychotherapy. Here, we review the currently available techniques, including those already in clinical use and those still under research. Techniques are grouped into the following categories: (1) seizure therapies, including electroconvulsive therapy and magnetic seizure therapy, (2) noninvasive techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial electric stimulation, (3) surgical approaches, including vagus nerve stimulation, epidural electrical stimulation, and deep brain stimulation, and (4) technologies on the horizon. Additionally, we discuss novel approaches to the optimization of each treatment, and new techniques that are under active investigation.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 01/2012; 37(1):102-16. · 6.99 Impact Factor
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ABSTRACT: The relationship between accuracy and confidence in psychophysical tasks traditionally has been assumed to be mainly positive, i.e., the two typically increase or decrease together. However, recent studies have reported examples of exceptions, where confidence and accuracy dissociate from each other. Explanations for such dissociations often involve dual-channel models, in which a cortical channel contributes to both accuracy and confidence, whereas a subcortical channel only contributes to accuracy. Here, we show that a single-channel model derived from signal detection theory (SDT) can also account for such dissociations. We applied transcranial magnetic stimulation (TMS) to the occipital cortex to disrupt the internal representation of a visual stimulus. The results showed that consistent with previous research, occipital TMS decreased accuracy. However, counterintuitively, it also led to an increase in confidence ratings. The data were predicted well by a single-channel SDT model, which posits that occipital TMS increased the variance of the internal stimulus distributions. A formal model comparison analysis that used information theoretic methods confirmed that this model was preferred over single-channel models, in which occipital TMS changed the signal strength or dual-channel models, which assume two different processing routes. Thus our results show that dissociations between accuracy and confidence can, at least in some cases, be accounted for by a single-channel model.
Journal of Neurophysiology 12/2011; 107(6):1556-63. · 3.32 Impact Factor
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ABSTRACT: Although electroconvulsive therapy (ECT) is a highly effective treatment for people with severe depression, many patients report that treatment-induced memory problems are the most disturbing and serious adverse effects, affecting quality of life after treatment and willingness to consent to further ECT sessions. To date, no intervention to mitigate these cognitive deficits has been developed. We introduce the methodology of a novel cognitive training program called Memory Training for ECT (Mem-ECT) that is based on cognitive training in seizure disorders. Mem-ECT is designed to help memories that are usually compromised after ECT to remain relatively preserved.
We evaluated the feasibility of implementing Mem-ECT in 8 adult patients with a diagnosis of major depressive disorder who underwent right unilateral ECT. This open pilot trial assessed recruitment procedures and treatment feasibility such as patient's burden and compliance, exercise length, and how best to integrate treatment sessions around the patient's schedule before undergoing ECT.
We found Mem-ECT to be fairly well tolerated by depressed inpatients and easily implemented within ECT treatment services.
We discuss issues for future development, including an ongoing treatment-masked controlled study we are conducting to test the efficacy of Mem-ECT. Developing a safe and effective behavioral strategy to minimize ECT's adverse effects on memory may make ECT a more easily tolerated treatment.
The journal of ECT 11/2011; 27(4):286-91. · 1.19 Impact Factor
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ABSTRACT: The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported.
This paper provides fundamental definitions and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol.
The biologic effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biologic effects of EM stimulation.
We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated.
Brain Stimulation 11/2011; 5(4):435-53. · 3.76 Impact Factor
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ABSTRACT: Background: Deep brain stimulation (DBS) for treatment-resistant depression (TRD) is the focus of great interest and numerous studies. Given the state of this research, the risks of DBS, the uncertainty of direct benefits, and the potential for therapeutic misconception (TM), examination of research participants’ perspectives is critical to addressing concerns about the adequacy of consent among people with TRD. Methods: Among 31 participants considering DBS studies at two sites, self-report questionnaires were used to examine three dimensions of TM (eight true/false items). Additional Likert-scale items assessed perceptions of risks, potential benefits, and altruistic motivations. Results: Participants correctly identified the surgery itself as the riskiest study procedure, although only four participants rated the surgery as “high risk.” Most participants rated the entire DBS study as “moderate” or lower risk. Participants rated the likelihood of others benefiting in the future more strongly than they did the likelihood of personal benefit. Participants held positive attitudes toward research, and were moderately altruistic. Nearly two-thirds of the 31 participants (64.5%) answered at least one of the true/false TM items incorrectly. Conclusions: Individuals considering DBS studies for TRD demonstrated reasonable perceptions of risks and benefits, distinguished among procedural risks, and expressed hopes for personal benefit as well as altruism. Findings related to TM were mixed: Participants understood the experimental stage of DBS for depression and endorsed the possibility of no personal benefit, yet there was some evidence for TM. Although these findings are reassuring, investigators must nevertheless remain vigilant about identifying and addressing potential misconceptions.
AJOB Primary Research. 10/2011; 2(4):33-41.
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William M McDonald,
Valerie Durkalski,
Edward R Ball,
Paul E Holtzheimer,
Martina Pavlicova, Sarah H Lisanby,
David Avery,
Berry S Anderson,
Ziad Nahas,
Paul Zarkowski,
Harold A Sackeim,
Mark S George
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ABSTRACT: To assess the efficacy of increasing the number of fast left repetitive transcranial magnetic stimulations (rTMS) (10 Hz @ 120% of motor threshold (MT) over the left dorsolateral prefrontal cortex (DLPFC)) needed to achieve remission in treatment-resistant depression (TRD). And, to determine if patients who do not remit to fast left will remit using slow right rTMS (1 Hz @ 120% MT over the right DLPFC).
Patients were part of a multicenter sham-controlled trial investigating the efficacy of fast left rTMS. Patients who failed to meet minimal response criteria in the sham-controlled study could enroll in this open fast left rTMS study for an additional 3-6 weeks. Patients who failed to remit to fast left could switch to slow right rTMS for up to 4 additional weeks. The final outcome measure was remission, defined as a HAM-D score of <3 or 2 consecutive HAM-D scores less than 10.
Forty-three of 141 (30.5%) patients who enrolled in the open phase study eventually met criteria for remission. Patients who remitted during fast left treatment received a mean of 26 active treatments (90,000 pulses). Twenty-six percent of patients who failed fast left remitted during slow right treatment.
The total number of rTMS stimulations needed to achieve remission in TRD may be higher than is used in most studies. TRD patients who do not respond to fast left rTMS may remit to slow right rTMS or additional rTMS stimulations.
Depression and Anxiety 09/2011; 28(11):973-80. · 4.18 Impact Factor
