The assessment of resistance to antidepressant treatment: Rationale for the Antidepressant Treatment History Form: Short Form (ATHF-SF).

There is considerable diversity in how treatment-resistant depression (TRD) is defined. However, every definition incorporates the concept that patients with TRD have not benefited sufficiently from one or more adequate trials of antidepressant treatment. This review examines the issues fundamental to the systematic evaluation of antidepressant treatment adequacy and resistance. These issues include the domains of interventions deemed effective in treatment of major depressive episodes (e.g., pharmacotherapy, brain stimulation, and psychotherapy), the subgroups of patients for whom distinct adequacy criteria are needed (e.g., bipolar vs. unipolar depression, psychotic vs. nonpsychotic depression), whether trials should be rated dichotomously as adequate or inadequate or on a potency continuum, whether combination and augmentation strategies require specific consideration, and the criteria used to evaluate the adequacy of treatment delivery (e.g., dose, duration), trial adherence, and clinical outcome. This review also presents the Antidepressant Treatment History Form: Short-Form (ATHF-SF), a completely revised version of an earlier instrument, and details how these fundamental issues were addressed in the ATHF-SF.

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation.

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans and can be assessed using transcranial magnetic stimulation (TMS). Given the role of distal leg muscles in upright postural and dynamic tasks, such as walking, a growing research interest in the assessment and modulation of the corticospinal tracts relative to the function of these muscles has emerged in the last decade. However, methodological parameters used in previous work have varied across studies making the interpretation of results from cross-sectional and longitudinal studies less robust. Therefore, use of a standardized TMS protocol specific to the assessment of leg muscles' corticomotor response (CMR) will allow for direct comparison of results across studies and cohorts. The objective of this paper is to present a protocol that provides the flexibility to simultaneously assess the bilateral CMR of two main ankle antagonistic muscles, the tibialis anterior and soleus, using single pulse TMS with a neuronavigation system. The present protocol is applicable while the examined muscle is either fully relaxed or isometrically contracted at a defined percentage of maximum isometric voluntary contraction. Using each subject's structural MRI with the neuronavigation system ensures accurate and precise positioning of the coil over the leg cortical representations during assessment. Given the inconsistency in CMR derived measures, this protocol also describes a standardized calculation of these measures using automated algorithms. Though this protocol is not conducted during upright postural or dynamic tasks, it can be used to assess bilaterally any pair of leg muscles, either antagonistic or synergistic, in both neurologically intact and impaired subjects.

Estimating resting motor thresholds in transcranial magnetic stimulation research and practice: a computer simulation evaluation of best methods.

OBJECTIVES: Resting motor threshold is the basic unit of dosing in transcranial magnetic stimulation (TMS) research and practice. There is little consensus on how best to estimate resting motor threshold with TMS, and only a few tools and resources are readily available to TMS researchers. The current study investigates the accuracy and efficiency of 5 different approaches to motor threshold assessment for TMS research and practice applications. METHODS: Computer simulation models are used to test the efficiency and accuracy of 5 different adaptive parameter estimation by sequential testing (PEST) procedures. For each approach, data are presented with respect to the mean number of TMS trials necessary to reach the motor threshold estimate as well as the mean accuracy of the estimates. RESULTS: A simple nonparametric PEST procedure appears to provide the most accurate motor threshold estimates, but takes slightly longer (on average, 3.48 trials) to complete than a popular parametric alternative (maximum likelihood PEST). Recommendations are made for the best starting values for each of the approaches to maximize both efficiency and accuracy. CONCLUSIONS: In light of the computer simulation data provided in this article, the authors review and suggest which techniques might best fit different TMS research and clinical situations. Lastly, a free user-friendly software package is described and made available on the world wide web that allows users to run all of the motor threshold estimation procedures discussed in this article for clinical and research applications.

A high resolution assessment of the repeatability of relative location and intensity of transcranial magnetic stimulation-induced and volitionally induced blood oxygen level-dependent response in the motor cortex.

OBJECTIVE: Using functional magnetic resonance imaging, we assessed variation in location and intensity of blood oxygen level-dependent contrast associated with movements induced by transcranial magnetic stimulation or volition. BACKGROUND: Anatomic location and within-subject repeatability of blood oxygen level-dependent responses induced by transcranial magnetic stimulation comprise critical information to the use of interleaved transcranial magnetic stimulation/functional magnetic resonance imaging as a neuroscience tool. METHODS: Eleven healthy adults were scanned 3 times each at 1.5 T. Interleaved with functional magnetic resonance imaging, 1-Hz transcranial magnetic stimulation was applied over motor cortex. VOL was alternated with transcranial magnetic stimulation over the scans. RESULTS: Intra-subject standard deviations in blood oxygen level-dependent locations ranged between 3 and 6 millimeters, allowing localization to subregions of the motor strip. Coil placement relative to blood oxygen level-dependent location varied more than blood oxygen level-dependent location (sdx = 9.5mm, sdy = 8.7 mm, sdz = 9.0mm) with consistent anterior displacement (dy = 21.8 mm, P = <0.025). Analysis of variance did not detect significant differences between transcranial magnetic stimulation and VOL blood oxygen level-dependent locations or intensities, in contrast to significant intensity differences detected in auditory blood oxygen level dependence. CONCLUSION: The high repeatability of location of transcranial magnetic stimulation-induced blood oxygen level-dependent activation suggests that transcranial magnetic stimulation/functional magnetic resonance imaging stimulation can be used as a precise tool in investigation of cortical mechanisms. The similarity between VOL and transcranial magnetic stimulation suggests that transcranial magnetic stimulation may act through natural brain movement circuits.

Decision analysis of the cost-effectiveness of repetitive transcranial magnetic stimulation versus electroconvulsive therapy for treatment of nonpsychotic severe depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a new treatment with promise for resistant depression. OBJECTIVE: We tested the economic feasibility of this new method compared with electroconvulsive therapy (ECT). METHOD: An economic decision analysis was used to compare the costs of three different treatment strategies for nonpsychotic severe depression. The strategies were: ECT alone; rTMS alone; and rTMS followed by ECT for nonresponders (rTMS-to-ECT). We calculated 12-month costs and quality adjusted life years (QALYs) for the three treatment options for all nonpsychotic, severely depressed United States patients who would have otherwise undergone ECT. A sensitivity analysis was performed to test the degree of change in outcome with various parameter changes. RESULTS: The additional cost of using ECT alone compared with rTMS alone was 460,031 US dollars per quality adjusted year of life gained. For ECT versus rTMS-to-ECT, there was both an increased cost and a loss of 1,538 QALYs with ECT alone. The sensitivity analysis revealed the model to be robust with various parameter changes. CONCLUSION: If rTMS were to be made widely available clinically in the US, it would offer a substantial economic benefit over ECT in treating resistant depression. Using rTMS-to-ECT offers not only an economic advantage but also an increase in QALYs. This analysis suggests that rTMS would be a cost-effective treatment for depression compared with the current option of ECT alone.