Efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction for Depression Symptoms and Sleep-Wake Disruption in Older and Younger Adults: Secondary Age-Stratified Analysis of a Randomized Controlled Trial.

OBJECTIVE: Perform a secondary analysis examining the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for depression symptom responses, and explore changes in potential target mechanisms. DESIGN: Secondary analysis of a randomized controlled trial with convenience age subsamples (younger (20-49 year; n = 52) versus and older (50-71 years; n = 35)). SETTING: Community mental health clinics. PARTICIPANTS: Eighty-seven adults with serious mental illness. INTERVENTION: TranS-C versus treatment as usual (TAU). MEASUREMENTS: Outcomes were depression symptoms (Quick Inventory of Depression Symptoms), insomnia symptoms (Insomnia Severity Index), and objective sleep-wake rhythm measures (interdaily stability and relative amplitude). RESULTS: Depression response rates (≥50% symptom reductions) were higher in the TranS-C (35.0%) than the TAU (8.8%) group 6-months postintervention (χ2 = 10.3, p = 0.001). There was a medium effect of TranS-C versus TAU on depression symptoms 6-months postintervention (Cohen's d = -0.40, 95% confidence interval (CI): -0.81, 0.01). In both age groups, there were large treatment effects on insomnia symptoms post-treatment (Cohen's d >0.90). In the older subsample, there were additionally medium treatment effects on post-treatment interdaily stability (Cohen's d = 0.60, 95% CI: -0.11, 1.61). Post-treatment reductions in insomnia symptoms correlated with depression symptom reduction 6-months later in the younger subsample (Spearman rho = 0.59, n = 20, p = 0.008). In older adults, postintervention increases in interdaily stability correlated with depression symptom reductions 6-months later (Spearman rho = -0.52, n = 15, p = 0.049). CONCLUSION: Confirmatory trials are needed, given the low age-specific sample sizes here, to determine if TranS -C's produces durable depression responses by increasing sleep-wake rhythm stability in older adults and improving insomnia symptoms in younger adults. BRIEF ARTICLE SUMMARY: The authors evaluated preliminary efficacy of a behavioral intervention that targets sleep/sleep-wake rhythms, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C), for depression symptoms in people with serious mental illness. TranS-C was associated with higher depression response rates than treatment as usual 6-months postintervention. The degree of depression symptom response 6-months later was related to the degree of treatment phase improvements in interdaily stability (in older adults) and reduction in insomnia severity (in younger adults). A pragmatic nonpharmacologic intervention, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction, has preliminary efficacy for improving sleep-wake factors and depression symptoms.

Medical Expenditures Associated with Attention-Deficit/Hyperactivity Disorder Among Adults in the United States by Age, 2015-2019.

BACKGROUND: Attention-deficit hyperactivity disorder is a common disorder that affects both children and adults. However, for adults, little is known about ADHD-attributable medical expenditures. OBJECTIVE: To estimate the medical expenditures associated with ADHD, stratified by age, in the US adult population. DESIGN: Using a two-part model, we analyzed data from Medical Expenditure Panel Survey for 2015 to 2019. The first part of the model predicts the probability that individuals incurred any medical costs during the calendar year using a logit model. The second part of the model estimates the medical expenditures for individuals who incurred any medical expenses in the calendar year using a generalized linear model. Covariates included age, sex, race/ethnicity, geographic region, Charlson comorbidity index, insurance, asthma, anxiety, and mood disorders. PARTICIPANTS: Adults (18 +) who participated in the Medical Expenditure Panel Survey from 2015 to 2019 (N = 83,776). MAIN MEASURES: Overall and service specific direct ADHD-attributable medical expenditures. KEY RESULTS: A total of 1206 participants (1.44%) were classified as having ADHD. The estimated incremental costs of ADHD in adults were $2591.06 per person, amounting to $8.29 billion nationally. Significant adjusted incremental costs were prescription medication ($1347.06; 95% CI: $990.69-$1625.93), which accounted for the largest portion of total costs, and office-based visits ($724.86; 95% CI: $177.75-$1528.62). The adjusted incremental costs for outpatient visits, inpatient visits, emergency room visits, and home health visits were not significantly different. Among older adults (31 +), the incremental cost of ADHD was $2623.48, while in young adults (18-30), the incremental cost was $1856.66. CONCLUSIONS: The average medical expenditures for adults with ADHD in the US were substantially higher than those without ADHD and the incremental costs were higher in older adults (31 +) than younger adults (18-30). Future research is needed to understand the increasing trend in ADHD attributable cost.

The burden of untreated insomnia disorder in a sample of 1 million adults: a cohort study.

BACKGROUND: Insomnia disorder is a highly prevalent, significant public health concern associated with substantial and growing health burden. There are limited real-world data assessing the burden of insomnia disorder on daytime functioning and its association with comorbidities. The objective of this study was to leverage large-scale, real-world data to assess the burden of untreated insomnia disorder in terms of daytime impairment and clinical outcomes. METHODS: This United States medical claims database study compares patients diagnosed with insomnia disorder but not receiving treatment ('untreated insomnia' cohort) to patients without an insomnia disorder diagnosis and without treatment ('non-insomnia' cohort). International Classification of Disease, Tenth Revision codes were used as a proxy to represent the three symptom domains (Sleepiness, Alert/Cognition, Mood) of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), a newly developed and validated tool used in clinical studies to assess daytime functioning in insomnia disorder. Chronic Fatigue (R53.83) and Other Fatigue (R53.83), Somnolence (R40.0) and Disorientation (R41.0) were selected as categories representing one or more IDSIQ domains. Clinical outcomes included cardiovascular events, psychiatric disorders, cognitive impairment and metabolic disorders. RESULTS: Approximately 1 million patients were included (untreated insomnia: n = 139,959; non-insomnia: n = 836,975). Compared with the 'non-insomnia' cohort, the 'untreated insomnia' cohort was more likely to experience daytime impairments, with mean differences in occurrences per 100 patient-years for: (a) fatigue, at 27.35 (95% confidence interval [CI] 26.81, 27.77, p < 0.01); (b) dizziness, at 4.66 (95% CI 4.40, 4.90, p < 0.01); (c) somnolence, at 4.18 (95% CI 3.94, 4.43, p < 0.01); and (d) disorientation, at 0.92 (95% CI 0.77, 1.06, p < 0.01). During the 1-year look-back period, patients in the 'untreated insomnia' cohort were also more likely to have been diagnosed with arterial hypertension (40.9% vs. 26.3%), psychiatric comorbidities (40.1% vs. 13.2%), anxiety (29.2% vs. 8.5%), depression (26.1% vs. 8.1%) or obesity (21.3% vs. 11.1%) compared with those in the 'non-insomnia' cohort. CONCLUSIONS: This large-scale study confirms the substantial burden of insomnia disorder on patients in a real-world setting, with significant daytime impairment and numerous comorbidities. This reinforces the need for timely insomnia disorder diagnosis and treatments that improve both sleep, as well as daytime functioning.

Do Placebos Primarily Affect Subjective as Opposed to Objective Measures? A Meta-Analysis of Placebo Responses in Insomnia RCTs.

INTRODUCTION: Little is known about the relative magnitude of placebo responses on objective and subjective measures of sleep continuity. To address this issue, the pre-post effects of placebos on objective and subjective measures (i.e., polysomnography [PSG] and sleep diaries) were evaluated meta-analytically. The guiding hypothesis was that large responses would be observed on sleep diary measures and small responses would be observed on PSG measures. METHODS: PubMed searches, 1967-2016, yielded 329 possible articles, 17 of which met the inclusion and exclusion criteria for the present analysis (including 879 subjects with PSG data, 1,209 subjects with diary data, and six studies with both PSG and sleep diary data). Average change and weighted effect sizes (ESs) were computed via modeling for sleep latency (SL), wake after sleep onset (WASO) and total sleep time (TST). RESULTS: Pre-to-post change on PSG measures were: SL -13.7 min., ES = -0.37; WASO -14.3 min., ES = -0.36; and TST 29.8 min., ES = 0.50. Pre-to-post change on sleep diary measures were: SL -13.5 min., ES = -0.36; WASO -13.3 min., ES = -0.20; and TST 25.5 min., ES = 0.36. The modeled average objective subjective difference per sleep continuity measure was less than 5 minutes. The modeled average objective subjective difference per sleep continuity measure (in effect sizes) was less than 0.17. DISCUSSION: The observed outcomes of this analysis suggest that placebos produce comparable effects on objective and subjective measures of sleep continuity. Thus, objective measures do not appear to protect against placebo responses. This being the case and given the importance of the subjective experience of illness severity and recovery, such data suggests that prospectively sampled sleep continuity data (sleep diaries) may be the optimal data for clinical trials, particularly when only one measure is possible.

The Role of the Autonomic Nervous System in the Mediation of the Resolution of Suicidal Ideation With Electroconvulsive Therapy: A Hypothesis and Review of Heart Rate Variability Over a Course of Electroconvulsive Therapy.

ABSTRACT: Longitudinal observational studies have shown a meaningful decrease in suicidal thinking and suicidal behavior after receipt of electroconvulsive therapy (ECT). The antisuicide effect of ECT may be related to success in the global relief of the presenting syndrome such as depressive or psychotic illness. However, it is possible that the antisuicide effect is specific to ECT per se, over and above the relief of the clinical syndrome. Electroconvulsive therapy is associated with many observable neurochemical and physiologic effects, and some of these may plausibly be specifically linked to an antisuicide effect. The phenomenon of physiologic hyperarousal has been named as a candidate mechanism driving the risk for suicide. Hyperarousal is associated with decreased neuropsychological executive function responsible for response inhibition and can lead to impulsive action. The level of arousal within the autonomic nervous system (ANS) can be assayed with the pupillary light reflex, electrodermal activity, or with heart rate variability (HRV). This article summarizes the literature on the effects of ECT on HRV 24 to 72 hours after a course of ECT and finds evidence for increases in HRV, which indicates lower levels of arousal in the ANS. This finding suggests that ECT-related reductions in ANS arousal, presumably with corresponding improvements in response inhibition, may be one mechanism whereby ECT reduces risk for suicide.

Relationships among insomnia, executive function, and suicidal ideation in depressed outpatients: A mediation analysis.

Insomnia is a risk factor for suicide, and both are associated with cognitive problems. However, prior research has not examined insomnia, cognition, and suicidal ideation within one sample. We describe cross-sectional associations among insomnia, psychomotor speed, set shifting, and suicidal ideation in 85 depressed adults. Greater insomnia was associated with slower psychomotor speed, while slower psychomotor speed was associated with a greater level (i.e., elaboration of suicide planning) and intensity of suicidal ideation in the past week. Slower set shifting was associated with a greater level and intensity of suicidal ideation in the past week. Mediation analysis indicated that psychomotor speed and set shifting both had a significant total effect on the intensity of suicidal ideation in the past week; set shifting also had a significant total effect on the sum of intensity and suicidal ideation level in the past week. The level of insomnia explained only small percentages of the total effect of either psychomotor speed or set shifting on the intensity of suicidal ideation and the sum of intensity and suicidal ideation level. The findings in this sample demonstrate significant associations of slower psychomotor speed and set shifting with suicidal ideation, with negligible contribution from insomnia.

Major Depressive Disorder in the Older Adult Associated With Globus Pharyngeus and Weight Loss - An Indication for Electroconvulsive Therapy.

Aspiration pneumonia and extreme weight loss are risks whenever globus pharyngeus (GP) complicates major depressive disorder (MDD) in the older adult. The timely administration of electroconvulsive therapy (ECT) may reverse GP in this context. We review cases of GP in depressed older adults and describe both successful outcomes, as well as a fatal outcome associated with delays in offering ECT. MDD in the older adult complicated by GP and marked weight loss, or repeated aspiration, should be considered an urgent indication for ECT.

Longitudinal Neurocognitive Effects of Combined Electroconvulsive Therapy (ECT) and Pharmacotherapy in Major Depressive Disorder in Older Adults: Phase 2 of the PRIDE Study.

OBJECTIVE: There is limited information regarding neurocognitive outcomes of right unilateral ultrabrief pulse width electroconvulsive therapy (RUL-UB ECT) combined with pharmacotherapy in older adults with major depressive disorder. We report longitudinal neurocognitive outcomes from Phase 2 of the Prolonging Remission in Depressed Elderly (PRIDE) study. METHOD: After achieving remission with RUL-UB ECT and venlafaxine, older adults (≥60 years old) were randomized to receive symptom-titrated, algorithm-based longitudinal ECT (STABLE) plus pharmacotherapy (venlafaxine and lithium) or pharmacotherapy-only. A comprehensive neuropsychological battery was administered at baseline and throughout the 6-month treatment period. Statistical significance was defined as a p-value of less than 0.05 (two-sided test). RESULTS: With the exception of processing speed, there was statistically significant improvement across most neurocognitive measures from baseline to 6-month follow-up. There were no significant differences between the two treatment groups at 6 months on measures of psychomotor processing speed, autobiographical memory consistency, short-term and long-term verbal memory, phonemic fluency, inhibition, and complex visual scanning and cognitive flexibility. CONCLUSION: To our knowledge, this is the first report of neurocognitive outcomes over a 6-month period of an acute course of RUL-UB ECT followed by one of 2 strategies to prolong remission in older adults with major depression. Neurocognitive outcome did not differ between STABLE plus pharmacotherapy versus pharmacotherapy alone over the 6-month continuation treatment phase. These findings support the safety of RUL-UB ECT in combination with pharmacotherapy in the prolonging of remission in late-life depression.

Development of Autonomic Nervous System Assays as Point-of-Care Tests to Supplement Clinical Judgment in Risk Assessment for Suicidal Behavior: A Review.

PURPOSE OF REVIEW: A biomarker point-of-care (POC) test that supplements the psychiatric interview and improves detection of patients at risk for suicide would be of value, and assays of autonomic nervous system (ANS) activity would satisfy the logistical requirements for a POC test. We performed a selective review of the available literature of ANS assays related to risk for suicide. RECENT FINDINGS: We searched PubMed and Web of Science with the strategy: "suicide OR suicidal" AND "electrodermal OR heart rate variability OR pupillometry OR pupillography." The search produced 119 items, 21 of which provided original data regarding ANS methods and suicide. These 21 studies included 6 for electrodermal activity, 14 for heart rate variability, and 1 for the pupillary light reflex. The 21 papers showed associations between ANS assays and suicide risk in a direction suggesting underlying hyperarousal in patients at risk for suicide. ANS assays show promise for future development as POC tests to supplement clinical decision making in estimating risk for suicide.

Transcranial Magnetic Stimulation Therapy of Major Depressive Disorder Improves Heart Rate Variability.

ABSTRACT: Transcranial magnetic stimulation is typically administered daily for 6 to 9 weeks with gradual resolution of major depressive disorder. However, there is little evidence to guide clinicians when clinical improvement is not forthcoming as the course proceeds. We describe a patient whose depression score remained unchanged after 10 single daily intermittent thetaburst transcranial magnetic stimulation sessions targeting F3 in the dorsolateral prefrontal cortex and our efforts to modify the technique and monitor progress with heart rate variability (HRV) measures. The motor threshold position and intensity were verified to be unchanged from the baseline visit. Stimulation of F3 and treatment target 6 cm anterior to the mapped motor cortex site seemed to slow heart rate and increase HRV equally. We increased the number of daily intermittent thetaburst pulse trains for the remainder of the treatment course, targeting the 6-cm target. Our patient subsequently improved, and we observed concurrent changes in HRV suggestive of enhanced parasympathetic activity. These improvements were found to be durable at 10-week follow-up.

A proposal for a novel approach to reduce burdens of care for people with dementia: A hypothesis.

Cognitive impairment of dementia patients affects their ability to communicate and cooperate with care. Dementia patients need a specialized communication to increase their cooperation during daily care and a scale to measure cooperation with care. To improve communication, we created and applied a digital communication platform (DCP) in an observational study. To measure cooperation with care, we created and tested psychometric properties of the Cooperation with Care Scale-Revised (CWCS-R) in an institutional review board-approved 6-week prospective study. DCP intervention was associated with decreased agitation and use of psychotropic medications for nursing home (NH) dementia patients. CWCS-R is both a reliable and valid tool to measure cooperation with care in NH dementia patients. Innovations in communication with dementia patients and a scale to measure cooperation with care could reduce burdens of care and improve quality of life for patients, their family members, and staff. It may potentially help decrease cost of dementia care.

Blinding and bias in a hypnotic clinical trial.

OBJECTIVES: Information is lacking regarding how commonly unblinding of treatment assignment occurs in hypnotic randomized clinic trials (RCTs). We now report the "best guesses" of clinical trial participants, versus study coordinators, versus study physicians in the study Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT). METHODS: REST-IT, a, 8-week double-blind RCT, compared zolpidem extended-release (ER) versus placebo at bedtime in 103 adults with major depressive disorder with insomnia and suicidal ideation, and who received open label selective serotonin reuptake inhibitors. At the conclusion of study participation, 89 of the participants in this study, the study coordinators, and the study physicians each independently recorded their "best guess" of the treatment assigned. RESULTS: Patients guessed correctly 58.4% of the time, coordinators 53.9% of the time, and physicians 49.4% of the time, and none were different from chance alone. Agreement between patient/coordinator, patient/doctor, and coordinator/doctor dyads were 75%-78% with no significant differences in agreement between the dyads. CONCLUSIONS: "Best guesses" of all parties were not different from chance, suggesting that the blind was maintained and that assessment bias was minimized in this RCT of zolpidem ER versus placebo. Our results may not apply to other hypnotics or other RCT designs.

Is There Evidence That Stimulus Parameters and Electrode Placement Affect the Cognitive Side Effects of Electroconvulsive Therapy in Patients With Schizophrenia and Schizoaffective Disorder?: A Systematic Review.

ABSTRACT: Seventy percent of patients with treatment-resistant schizophrenia do not respond to clozapine. Electroconvulsive therapy (ECT) can potentially offer significant benefit in clozapine-resistant patients. However, cognitive side effects can occur with ECT and are a function of stimulus parameters and electrode placements. Thus, the objective of this article is to systematically review published clinical trials related to the effect of ECT stimulus parameters and electrode placements on cognitive side effects. We performed a systematic review of the literature up to July of 2020 for clinical studies published in English or German examining the effect of ECT stimulus parameters and/or electrode placement on cognitive side effects in patients with schizophrenia or schizoaffective disorder. The literature search generated 3 randomized, double-blind, clinical trials, 1 randomized, nonblinded trial, and 1 retrospective study. There are mixed findings regarding whether pulse width and stimulus dose impact on cognitive side effects. One study showed less cognitive side effect for right unilateral (RUL) than bitemporal (BT) electrode placement, and 2 studies showed a cognitive advantage for bifrontal (BF) compared with BT ECT. Only 1 retrospective study measured global cognition and showed post-ECT cognitive improvement with all treatment modalities using Montreal Cognitive Assessment in comparison to pre-ECT Montreal Cognitive Assessment scores. Current data are limited, but evolving. The evidence suggests that RUL or BF ECT have more favorable cognitive outcomes than BT ECT. Definitive larger clinical trials are needed to optimize parameter and electrode placement selection to minimize adverse cognitive effects.

Safe Administration of ECT in a Suicidal Patient With a Space-Occupying Astrocytoma.

ABSTRACT: Electroconvulsive therapy (ECT) can be lifesaving for patients suffering from treatment-resistant psychiatric conditions, especially acute suicidality or depression. However, space-occupying lesions pose risks associated with ECT use due in part to seizure-induced escalations in blood pressure with corresponding increases in cerebral blood flow and possibly intracranial pressure, subsequently increasing the risk of brain herniation. Here, we present the case of a patient with a left medial temporal lobe astrocytoma, worsening epileptic seizures, and nonepileptic seizures who underwent ECT for major depressive disorder and suicidality. The patient had improvement of depressive symptoms, resolution of suicidality, and brief cessation of nonepileptic seizures. Brief anterograde amnesia contributed to the termination of treatment. This case adds to the growing literature about the feasibility of ECT treatment in cerebral lesions prone to changes in intracranial pressure, such as the usually cystic astrocytomas.

The Effects of Focal Electrically Administered Seizure Therapy Compared With Ultrabrief Pulse Right Unilateral Electroconvulsive Therapy on Suicidal Ideation: A 2-Site Clinical Trial.

BACKGROUND: Preliminary data suggest that focal electrically administered seizure therapy (FEAST) has antidepressant effects and less adverse cognitive effects than traditional forms of electroconvulsive therapy (ECT). This study compared the impact of FEAST and ultrabrief pulse, right unilateral (UB-RUL) ECT on suicidal ideation. METHODS: At 2 sites, patients in a major depressive episode were treated openly with FEAST or UB-RUL ECT, depending on their preference. The primary outcome measure was scores on the Beck Scale for Suicide Ideation (SSI). Scores on the suicide item of the Hamilton Rating Scale for Depression (HRSD-SI) provided a secondary outcome measure. RESULTS: Thirty-nine patients were included in the intent-to-treat sample (FEAST, n = 20; UB-RUL ECT, n = 19). Scores on both the SSI and HRSD-SI were equivalently reduced with both interventions. Both responders and nonresponders to the interventions showed substantial reductions in SSI and HRSD-SI scores, although the magnitude of improvement was greater among treatment responders. CONCLUSIONS: Although limited by the open-label, nonrandomized design, FEAST showed comparable effects on suicidal ideation when compared with routine use of UB-RUL ECT. These results are encouraging and support the need for further research and a noninferiority trial.

Achieving Equity in Informed Consent: A Culturally-Informed Perspective for the Consideration and Consent of Minority Patients for Electroconvulsive Therapy.

Electroconvulsive therapy (ECT) is highly efficacious to treat severe depression in older adults. Yet, patients of ethnic and racial minorities are consistently underrepresented amongst those who receive ECT across all age groups. One strong hypothesis to explain this disparity is that minority patients are less likely to trust medical professionals and are therefore less likely to consent for ECT. Increasing participation of depressed, elderly, minority patients is uniquely challenging. Senior minority individuals have survived decades of medical and social injustices that no other demographic, specifically younger minorities or clinically-matched Caucasian peers, can truly comprehend from a first-hand perspective. This article provides a perspective based in cultural translational science to conversations of informed consent for ECT that removes our self-imposed stigma against discussing past and ongoing injustices with minority patients. Reducing disparities to geriatric minorities through equity of informed consent means that clinicians must validate the unique minority experience in medicine as it pertains to agreeing to a treatment modality as emotionally, socially, and historically laden as ECT.

Neurocognitive Effects of Combined Electroconvulsive Therapy (ECT) and Venlafaxine in Geriatric Depression: Phase 1 of the PRIDE Study.

OBJECTIVE: There is limited information regarding the tolerability of electroconvulsive therapy (ECT) combined with pharmacotherapy in elderly adults with major depressive disorder (MDD). Addressing this gap, we report acute neurocognitive outcomes from Phase 1 of the Prolonging Remission in Depressed Elderly (PRIDE) study. METHODS: Elderly adults (age ≥60) with MDD received an acute course of 6 times seizure threshold right unilateral ultrabrief pulse (RUL-UB) ECT. Venlafaxine was initiated during the first treatment week and continued throughout the study. A comprehensive neurocognitive battery was administered at baseline and 72 hours following the last ECT session. Statistical significance was defined as a two-sided p-value of less than 0.05. RESULTS: A total of 240 elderly adults were enrolled. Neurocognitive performance acutely declined post ECT on measures of psychomotor and verbal processing speed, autobiographical memory consistency, short-term verbal recall and recognition of learned words, phonemic fluency, and complex visual scanning/cognitive flexibility. The magnitude of change from baseline to end for most neurocognitive measures was modest. CONCLUSION: This is the first study to characterize the neurocognitive effects of combined RUL-UB ECT and venlafaxine in elderly adults with MDD and provides new evidence for the tolerability of RUL-UB ECT in an elderly sample. Of the cognitive domains assessed, only phonemic fluency, complex visual scanning, and cognitive flexibility qualitatively declined from low average to mildly impaired. While some acute changes in neurocognitive performance were statistically significant, the majority of the indices as based on the effect sizes remained relatively stable.

Treating Posttraumatic Stress Disorder Symptoms With Low Amplitude Seizure Therapy (LAP-ST) Compared With Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial.

OBJECTIVES: An important barrier to further studying electroconvulsive therapy (ECT) in posttraumatic stress disorder (PTSD) is the cognitive adverse effects. However, recent data suggest that low amplitude seizure therapy (LAP-ST) has no or minimal cognitive adverse effects. The aims of this report were to examine the efficacy of LAP-ST in PTSD and to compare LAP-ST with standard right unilateral (RUL) ECT using a pilot randomized clinical trial. METHODS: Patients were randomized to LAP-ST or RUL ECT. Posttraumatic stress disorder was assessed using clinical interview based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and symptom severity with PTSD Checklist (PCL). The scores pertaining to PCL were analyzed using descriptive analysis for this pilot study. RESULTS: Eleven patients consented to be enrolled. Seven were randomly allocated to LAP-ST or RUL ECT. Five completed the study and had completed PCL before and after the course. In both groups, PTSD symptoms showed fast improvement. The effect size of improvement seems promising. The mean baseline PCL score for patients in the LAP-ST group was 42.5 (SD = 16.26) and the mean end point PCL score after treatment was 31 (SD = 15.56). The mean baseline PCL score for patients in the standard RUL ECT group was 64.7 (SD = 1.15) and the mean end point was 41 (SD = 15.62). CONCLUSIONS: Both LAP-ST and standard RUL ECT showed reduction in PTSD symptoms with fast improvement. This first PTSD LAP-ST study adds support to the prior LAP-ST proof-of-concept clinical trial that LAP-ST can produce effective therapeutic outcomes. Replication of this trial is warranted in larger clinical trials (ClinicalTrials.gov ID: NCT02583490).

Revising rapid-onset dystonia-parkinsonism: Broadening indications for ATP1A3 testing.

BACKGROUND AND OBJECTIVES: Rapid-onset dystonia-parkinsonism (RDP) is caused by mutations in the ATP1A3 gene, which codes for the α-3 subunit of the Na+ /K+ ATPase. It has been characterized by rapid-onset bulbar dysfunction, limb dystonia, bradykinesia, and a rostrocaudal spatial gradient of expression, usually after a physiologic trigger. We reexamined whether these features were in fact characteristic. METHODS: We characterized phenotypic variation within a cohort of 50 ATP1A3 mutation-positive individuals (carriers) and 44 mutation-negative family members (noncarriers). Potential participants were gathered through referral for clinical suspicion of RDP or alternating hemiplegia of childhood. Inclusion criteria were having a ATP1A3 mutation or being a family member of such an individual. RESULTS: We found RDP is underdiagnosed if only "characteristic" patients are tested. Rapid onset and bulbar predominance were not universally present in carriers. Among those with at least mild symptoms of dystonia, rostrocaudal severity gradient was rare (7%). Symptoms began focally but progressed to be generalized (51%) or multifocal (49%). Arm (41%) onset was most common. Arms and voice were typically most severely affected (48% and 44%, respectively). Triggers preceded onset in 77% of the participants. Rapid onset, dystonia, parkinsonism, bulbar symptoms, headaches, seizures, frontal impairment, and a history of mood disorder and a history of psychosis were more common in carriers. Approximately half of the proband mutations occurred de novo (56%). CONCLUSIONS: Our findings suggest that patients should not be excluded from ATP1A3 testing because of slow onset, limb onset, absent family history, or onset in middle adulthood. RDP should be strongly considered in the differential for any bulbar dystonia. © 2019 International Parkinson and Movement Disorder Society.