Daniel F. Maixner

Daily left prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: Clinical predictors of outcome in a multisite, randomized controlled clinical trial

Randomized controlled trials support the antidepressant efficacy of transcranial magnetic stimulation (TMS); however, there is individual variability in the magnitude of response. Examination of response predictors has been hampered by methodological limitations such as small sample sizes and single-site study designs. Data from a multisite sham-controlled trial of the antidepressant efficacy of TMS provided an opportunity to examine predictors of acute outcome. An open-label extension for patients who failed to improve provided the opportunity for confirmatory analysis. Treatment was administered to the left dorsolateral prefrontal cortex at 10 pulses per second, 120% of motor threshold, for a total of 3000 pulses per day. Change on the Montgomery–Asberg Depression Rating Scale after 4 weeks was the primary efficacy outcome. A total of 301 patients with nonpsychotic unipolar major depression at 23 centers were randomized to active or sham TMS. Univariate predictor analyses showed that the degree of prior treatment resistance in the current episode was a predictor of positive treatment outcome in both the controlled study and the open-label extension trial. In the randomized trial, shorter duration of current episode was also associated with a better outcome. In the open-label extension study, absence of anxiety disorder comorbidity was associated with an improved outcome, but duration of current episode was not. The number of prior treatment failures was the strongest predictor for positive response to acute treatment with TMS. Shorter duration of current illness and lack of anxiety comorbidity may also confer an increased likelihood of good antidepressant response to TMS.

Response of Depression to Electroconvulsive Therapy: A Meta-Analysis of Clinical Predictors

OBJECTIVE Roughly one-third of individuals with depression do not respond to electroconvulsive therapy (ECT). Reliable predictors of ECT response would be useful for patient selection, but have not been demonstrated definitively. We used meta-analysis to measure effect sizes for a series of clinical predictors of ECT response in depression. DATA SOURCES PubMed was searched systematically to identify studies published after 1980 that tested at least 1 clinical predictor of response to ECT. STUDY SELECTION Of 51 studies identified, 32 were compatible with meta-analysis. DATA EXTRACTION The weighted mean odds ratio (OR) or standardized mean difference (SMD) was computed for each of 10 clinical predictors, based on dichotomous outcomes (responder vs nonresponder). Statistical analyses examined robustness, bias, and heterogeneity. RESULTS Shorter depressive episode duration predicted higher ECT response rate (SMD = -0.37, 7 studies, 702 subjects, P = 4 × 10(-6)). History of medication failure in the current episode was also a robust predictor: response rates were 58% and 70%, respectively, for those with and without medication failure (OR = 0.56, 11 studies, 1,175 subjects, P = 1 × 10(-5)). Greater age and psychotic features were weakly associated with higher ECT response rates, but heterogeneity was notable. Bipolar diagnosis, sex, age at onset, and number of previous episodes were not significant predictors. Analyses of symptom severity and melancholic features were inconclusive due to study heterogeneity. CONCLUSIONS Longer depressive episodes and medication failure at baseline are robust predictors of poor response to ECT, with effect sizes that are modest but clinically relevant. Patient characteristics used traditionally such as age, psychosis, and melancholic features are less likely to be clinically useful. More robust clinical and biological predictors are needed for management of depressed patients considering ECT.

Auditory memory decrements, without dissimulation, among patients with major depressive disorder

Questions have been raised about whether poor performance on memory tasks by individuals with major depressive disorder (MDD) might be the result of poor or variable effort or disease-related disruption of neural circuits supporting memory functions. The present study examined performance on a measure of task engagement and on an auditory memory task among 45 patients with MDD (M age = 47.82, SD = 19.55) relative to 32 healthy controls (HC; M age = 51.03, SD = 22.09). One-hundred percent of HC and MDD volunteers performed above the threshold for adequate effort on a formal measure of task engagement. The MDD subjects performed significantly more poorly than the HC subjects on an auditory learning and memory test. The present results suggest that auditory memory difficulties do occur among those with MDD and that decrements in performance in this group may be related to factors other than lack of effort.

ECT and mental retardation: a review and case reports.

Electroconvulsive therapy (ECT) in patients with mental retardation has received limited study and is a subject of controversy. Specific difficulties in using ECT for this patient population include diagnostic dilemmas, difficulties with measuring outcome and monitoring side effects, and problems with professional attitudes. We report our experience with two cases in which ECT was applied to treat severe psychotic and catatonic symptoms. In case 1, a 22-year-old male patient with a history of moderate mental retardation, bipolar disorder, and neuroleptic malignant syndrome was admitted to manage his disruptive behavior and psychotic symptoms. The patient responded well to six bilateral ECTs with diminution of his psychotic symptoms and behavioral disturbances. In Case 2, a 39-year-old female patient with a history of mental retardation, schizoaffective disorder, and catatonic symptoms successfully responded to 11 bilateral ECTs. We conclude that ECT can be used safely and effectively in patients with mental retardation and severe or refractory psychotic symptoms.

Relationship of seizure duration to antidepressant efficacy in electroconvulsive therapy

BACKGROUND A relationship between the anticonvulsant and antidepressant properties of electroconvulsive therapy (ECT) has been hypothesized. The goal of this study was to see whether the anticonvulsant effects of ECT could be measured in a clinical setting and whether there was any relationship between the anticonvulsant effects of ECT and the antidepressant response to it. METHODS We examined the temporal relationship between change in seizure duration (as an index of anticonvulsant activity) and improvement in Hamilton Rating Scale for Depression scores in a retrospective sample of 114 depressed patients who received 145 courses of ECT. A linear mixed effects model was utilized for analysis so that the repeated measures nature of the data could be taken into account. RESULTS Both seizure duration and depression scores decreased significantly through the course of ECT. However, no evidence was found for a relationship between decrease in seizure duration and clinical improvement as measured by Hamilton ratings. CONCLUSIONS The process underlying the reduction in seizure duration through a course of ECT may not be related to antidepressant efficacy.

Electroconvulsive Therapy Device Classification: Response to FDA Advisory Panel Hearing and Recommendations

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 Panels willingness to recommend reclassification of ECT devices to a less restrictive category. In addition, the NNDCs 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.

Onset of Catatonia at Puberty: Electroconvulsive Therapy Response in Two Autistic Adolescents

Catatonia is a syndrome of motor and behavioral disturbance. It is a poorly understood condition, which is underrecognized and may go untreated despite intensive medical workup and numerous unsuccessful medication trials. However, with treatments known to be effective, such as benzodiazepines and/or electroconvulsive therapy, patients may return to their baseline functioning. Autism and catatonia have been previously reported together. We report 2 patients with autism and mental retardation who developed catatonic symptoms at the onset of puberty. Both patients experienced persistent symptoms over several years and presented with a history of motor disturbance, functional decline, and episodic aggression. Both patients were treated with electroconvulsive therapy resulting in a positive response and functional improvement. Catatonia may persist as a chronic condition, lasting over several months or years, if not recognized and treated.

Catatonia following surgery for temporal lobe epilepsy successfully treated with electroconvulsive therapy

Catatonia is a psychomotor and behavioral syndrome associated with mood disorders, psychotic disorders, neurological disease, and general medical conditions. Catatonia has also been described as a manifestation of partial onset seizures. We describe a case of catatonia following successful epilepsy surgery. A 38-year-old patient with congenital hydrocephalus and left hippocampal sclerosis underwent selective left amygdalohippocampectomy for medically refractory seizures. Three days after surgery, she became progressively less interactive. Verbal output was dramatically reduced. She exhibited waxy flexibility, stupor, mutism, posturing, rigidity, negativism, and grimacing. Video/EEG monitoring showed no evidence of ongoing seizure activity. She was treated with high-dose benzodiazepines for presumed catatonia, but the behavioral pattern did not resolve. Subsequently the patient underwent a full course of electroconvulsive therapy. Catatonia resolved over the ensuing 3 weeks. Following discharge from the hospital, the patients global functioning returned to the premorbid level, and she has been seizure free for more than 4 years.

Cost-effectiveness of Electroconvulsive Therapy vs Pharmacotherapy/Psychotherapy for Treatment-Resistant Depression in the United States

Importance Electroconvulsive therapy (ECT) is a highly effective treatment for depression but is infrequently used owing to stigma, uncertainty about indications, adverse effects, and perceived high cost. Objective To assess the cost-effectiveness of ECT compared with pharmacotherapy/psychotherapy for treatment-resistant major depressive disorder in the United States. Design, Setting, and Participants A decision analytic model integrating data on clinical efficacy, costs, and quality-of-life effects of ECT compared with pharmacotherapy/psychotherapy was used to simulate depression treatment during a 4-year horizon from a US health care sector perspective. Model input data were drawn from multiple meta-analyses, randomized trials, and observational studies of patients with depression. Where possible, data sources were restricted to US-based studies of nonpsychotic major depression. Data were analyzed between June 2017 and January 2018. Interventions Six alternative strategies for incorporating ECT into depression treatment (after failure of 0-5 lines of pharmacotherapy/psychotherapy) compared with no ECT. Main Outcomes and Measures Remission, response, and nonresponse of depression; quality-adjusted life-years; costs in 2013 US dollars; and incremental cost-effectiveness ratios. Strategies with incremental cost-effectiveness ratios of

Changes in brain connectivity during a sham-controlled, transcranial magnetic stimulation trial for depression

100 000 per quality-adjusted life-year or less were designated cost-effective. Results Based on the Sequenced Treatment Alternatives to Relieve Depression trial, we simulated a population with a mean (SD) age of 40.7 (13.2) years, and 62.2% women. Over 4 years, ECT was projected to reduce time with uncontrolled depression from 50% of life-years to 33% to 37% of life-years, with greater improvements when ECT is offered earlier. Mean health care costs were increased by