The effect of zolpidem-CR on the suicide item of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia and suicidal ideation: Lessons learned.

The REST-IT study found the addition of zolpidem-controlled release (CR) provided a significant reduction in observer-rated measurement of suicidal ideation (the Columbia Suicide Severity Rating Scale) in 103 depressed outpatients with insomnia and suicidal ideation, but without significant change in a self-report measure of suicidal ideation (the Scale for Suicide Ideation). This secondary analysis of the REST-IT data examined the suicide item of another observer-rated scale, the Hamilton Rating Scale for Depression (HRSD), further clarifying the impact of insomnia-focused treatment on suicidal ideation. This analysis established a significant advantage for zolpidem-CR compared with placebo on the HRSD suicide item.

A review of clinical studies of electrodermal activity and transcranial magnetic stimulation.

There is a growing body of evidence indicative of changes in autonomic nervous system (ANS) activity in patients with disorders of the central nervous system (CNS). Non-invasive measures of the ANS, including heart rate variability (HRV), electrodermal activity (EDA), and pupillary light reflex (PLR) may have value as markers of symptom severity, subtype, risk profile, and/or treatment response. In this paper we provide an introduction into the anatomy and physiology of EDA and review the literature published after 2007 in which EDA was an outcome measure of cortical stimulation with transcranial magnetic stimulation (TMS). Eleven studies were included and considered regarding the potential of EDA as an outcome measure reflecting ANS activity in TMS research and treatment. These studies are summarized according to study population, experimental methodology, cortical region targeted, and correlation with other measures of ANS activity. Results indicate that EDA changes vary with the frequency and target of TMS. Inhibitory TMS to the dorsolateral prefrontal cortex (dlPFC) was the most common paradigm in these studies, consistently resulting in decreased EDA.

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.

Daytime autonomic nervous system functions differ among adults with and without insomnia symptoms.

STUDY OBJECTIVES: We gathered data to determine whether daytime assays of the autonomic nervous system would differ between persons with no vs modest insomnia symptoms and would correlate with the severity of insomnia symptoms in patients. METHODS: This report is composed of 2 studies. Study 1 conducted pupillary light reflex (PLR) measurements in community volunteers who were not seeking medical care. Study 2 contrasted PLR and heart rate variability in a different sample of community volunteers and a comparison sample of adults seeking outpatient care for insomnia and psychiatric problems. All measurements were taken between 3 and 5 pm. RESULTS: In Study 1, volunteers with modest insomnia symptom severity had a more rapid PLR average constriction velocity compared with those with no symptoms. In Study 2, lower heart rate variability, indicating higher levels of physiologic arousal, generally were in agreement with faster PLR average constriction velocity, both of which indicate higher levels of arousal. Insomnia symptom severity was highly correlated with faster average constriction velocity in the patient sample. CONCLUSIONS: These studies suggest that (1) daytime measurements of the autonomic nervous system differ between persons with modest vs no insomnia symptoms and (2) insomnia symptom severity is highly correlated with PLR. Daytime measurement of autonomic nervous system activity might allow for daytime point-of-care measurement to characterize the level of physiologic arousal to define a hyperarousal subtype of insomnia disorder. CITATION: McCall WV, Looney SW, Zulfiqar M, et al. Daytime autonomic nervous system functions differ among adults with and without insomnia symptoms. J Clin Sleep Med. 2023;19(11):1885-1893.

Reproducibility of the pupillary light reflex over short intervals in psychiatric patients and community volunteers.

The pupillary light reflex (PLR) is a method for measuring dynamic responses within the autonomic nervous system, and would have potential value as a point-of-care test in a psychiatry clinic if reproducible results could be obtained in a short period of time. We collected PLR from adult community volunteers and depressed outpatients with the purpose of demonstrating (1) that valid data could be obtained >90% of the time from both the community volunteers and the patients, and (2) that reproducible results could be obtained with repeated measurement over short periods of time. Valid data were captured for 90.3% of 76 participants, allowing for two attempts of the PLR per participant. Success rates were similar for depressed patients and community volunteers. Eighteen of these 76 participants provided repeated paired measurements after 5 and 10 min of dark adaptation, producing high correlations for maximum constriction velocity (MCV) between assay 1 and 2 (Pearson's r = 0.71, p < 0.001), but there was a significant 8% increase in velocity for MCV between assay 1 and 2 (∆ = 0.34 ± 0.59 mm/s, p < 0.05). In contrast, PLR measurements were stable when tested in a separate cohort of 21 additional participants at 10 and 15 min of dark adaptation with an MCV Pearson's correlation of r = 0.84, p < 0.001, with a nonsignificant 1% difference between the two time points. These findings indicate an acceptable rate of collecting valid and reproducible PLR data when contrasting two measurements of PLR after 10 or 15 min of dark adaptation in depressed and suicidal patients.

Electroconvulsive therapy for super refractory status epilepticus in pregnancy: case report and review of literature.

OBJECTIVE: We aim to describe use of electroconvulsive therapy (ECT) to treat super refractory status epilepticus (SRSE) in pregnancy and review the literature regarding utility and safety of ECT in refractory status epilepticus. BACKGROUND: Status epilepticus (SE) is a commonly encountered emergency in neuro-critical care world. Pharmacotherapy of status epilepticus in pregnancy is very challenging given the effect of the majority of antiepileptic drugs (AEDs) on fetal development. Although there has been growing evidence for use of ECT in status epilepticus, data about its utility in pregnancy is lacking. DESIGN/METHOD: A twenty-one year old Caucasian female with history of epilepsy presented at 8 weeks of gestation as status epilepticus (SE) after abrupt discontinuation of her AEDs. Treatment was initiated with standard regimen of benzodiazepine and levetiracetam, which was progressively expanded to include approximately 10 anti-epileptic drugs over the course of 30 days. The status epilepticus was super refractory to sedation. She underwent ECT on day 31 with remarkable improvement in electroencephalogram (EEG) pattern and resolution of status epilepticus following a single ECT session. We reviewed PubMed and collated case reports involving the use of ECT in status epilepticus with emphasis on differences in various confounding factors esp. etiology of status and age group. CONCLUSION: Our case is the first reported case of ECT for successful treatment of SRSE in pregnancy. While majority AEDs pose a significant maternal and fetal risk during pregnancy, ECT could be a potential frontline therapy for SE in pregnancy.

Impact of suboptimal or inappropriate treatment on healthcare resource use and cost among patients with uncomplicated urinary tract infection: an analysis of integrated delivery network electronic health records.

BACKGROUND: Although uncomplicated urinary tract infections (uUTIs; occurring in female patients without urological abnormalities or history of urological procedures or complicating comorbidities) are one of the most common community infections in the United States (US), limited data are available concerning associations between antibiotic resistance, suboptimal prescribing, and the economic burden of uUTI. We examined the prevalence of suboptimal antibiotic prescribing and antibiotic resistance and its effects on healthcare resource use and costs. METHODS: This retrospective cohort study utilized electronic health record data from a large Mid-Atlantic US integrated delivery network database, collected July 2016-March 2020. Female patients aged ≥ 12 years with a uUTI, who received ≥ 1 oral antibiotic treatment within ± 5 days of index uUTI diagnosis, and had ≥ 1 urine culture with antimicrobial susceptibility test, were eligible for inclusion in the study. The study examined the proportion of antibiotics that were inappropriately or suboptimally prescribed among patients with confirmed uUTI, and total healthcare costs (all-cause and UTI-related) within 6 months after a uUTI, stratified by antibiotic susceptibility and/or inappropriate or suboptimal treatment. Patient outcomes were assessed after 1:1 propensity score matching of patients with antibiotic-susceptible versus not-susceptible isolates and then by other covariates (e.g., demographics and recent healthcare use). A similar propensity score calculation was used to analyze the effect of inappropriate/suboptimal treatment on health outcomes. Costs were adjusted to 2020 US dollars ($). RESULTS: Among 2565 patients with a uUTI included in the analysis, the most commonly prescribed antibiotics were nitrofurantoin (61%), trimethoprim-sulfamethoxazole (19%), and ciprofloxacin (15%). More than one-third of the sample (40.2%) had isolates that were not-susceptible to ≥ 1 antibiotic indicated for treating patients with uUTI. Two-thirds (66.6%) of study-eligible patients were prescribed appropriate treatment; 29.9% and 11.9% were prescribed suboptimal and/or inappropriate treatment, respectively. Inappropriate or suboptimally prescribed patients had greater all-cause and UTI-related costs compared with appropriately prescribed patients. Differences were most striking among patients with antibiotic not-susceptible isolates. CONCLUSIONS: These findings highlight how the increasing prevalence of antibiotic resistance combined with suboptimal treatment of patients with uUTI increases the burden on healthcare systems. The finding underlines the need for improved prescribing accuracy by better understanding regional resistance rates and developing improved diagnostic tests.

Economic burden of antibiotic-not-susceptible isolates in uncomplicated urinary tract infection: Analysis of a US integrated delivery network database.

BACKGROUND: Uncomplicated urinary tract infections (uUTIs) are one of the most common bacterial infections in the United States (US). Contemporary data are important for understanding the health economic impact of antimicrobial-resistant uUTIs. We compared the economic burden among patients with uUTI isolates susceptible or not-susceptible to the initial antibiotic prescription. METHODS: This retrospective cohort study utilized electronic health record data (1 July 2016-31 March 2020) from a large Mid-Atlantic US integrated delivery network database. Patients were females aged ≥ 12 years with a uUTI, who received oral antibiotic treatment and had ≥ 1 urine culture within ± 5 days of diagnosis. The primary outcome was the difference in healthcare resource use and costs (all-cause, urinary tract infection [UTI]-related) among patients with susceptible versus not-susceptible isolates during the 6 months after the index uUTI diagnosis. Secondary outcomes included: pharmacy costs, hospital admissions and emergency department visits, as well as the probability of uUTI progressing to complicated UTI (cUTI) between patients with susceptible and not-susceptible isolates. Patient outcomes were compared using 1:1 propensity score matching. Winsorized costs were adjusted to 2020 quarter 1 US dollars ($). RESULTS: A total of 2565 patients were eligible for analysis. The propensity score-matched sample comprised 2018 patients, with an average age of 44.0 and 41.0 years for the susceptible and not-susceptible populations, respectively. In the 6 months post-index uUTI event, patients with not-susceptible isolates had significantly more all-cause prescriptions orders (+ 1.41 [P = 0.001]), UTI-related prescriptions orders (+ 0.26 [P < 0.001]) and a higher probability of all-cause inpatient (+ 1.4% [P = 0.009]), outpatient (+ 6.1% [P = 0.006]), or UTI-related outpatient (+ 3.7% [P = 0.039]) encounters. Patients with a uUTI and an antibiotic-not-susceptible isolate were significantly more likely to progress to cUTI than those with susceptible isolates (odds ratio: 2.35 [confidence interval: 1.66-3.33; P < 0.001]). Over 6 months, patients with not-susceptible versus susceptible isolates had significantly higher all-cause costs (+ $426 [P = 0.031]) and UTI-related costs (+ $157 [P = 0.034]). CONCLUSIONS: Patients with a uUTI caused by antibiotic-not-susceptible isolates had higher healthcare resource usage, costs, and increased likelihood of progressing to cUTI than those with antibiotic-susceptible isolates.

Role of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia in Forensic Psychiatry.

ABSTRACT: Long-term institutionalization of the forensic psychiatry patient population places a psychological burden on patients and family members as well as a financial burden on the health care system at large. Although electroconvulsive therapy is a well-established tool for patients with treatment-resistant schizophrenia, it is infrequently used in the forensic setting. This review serves to demonstrate an example of electroconvulsive therapy in combination with clozapine as a means of reducing length of hospitalization in a forensic psychiatric patient. Furthermore, this review will discuss factors limiting the prescribing of electroconvulsive therapy to this patient population including ethical considerations and availability.

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.

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.

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.

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.

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.

Clinicians' Racial Bias Contributing to Disparities in Electroconvulsive Therapy for Patients From Racial-Ethnic Minority Groups.

Patients from racial-ethnic minority groups undergo disparate electroconvulsive therapy (ECT) treatment compared with Caucasian peers. One leading hypothesis is that clinicians may unknowingly display racial bias when considering ECT for patients of color. Studies have consistently shown that patients of color face numerous racially driven, provider-level interpersonal and perceptual biases that contribute to clinicians incorrectly overdiagnosing them as having a psychotic-spectrum illness rather than correctly diagnosing a severe affective disorder. A patient's diagnosis marks the entry to evidence-based service delivery, and ECT is best indicated for severe affective disorders rather than for psychotic disorders. As a consequence of racially influenced clinician misdiagnosis, patients from racial-ethnic minority groups are underrepresented among those given severe affective diagnoses, which are most indicated for ECT referral. Evidence also suggests that clinicians may use racially biased treatment rationales when considering ECT after they have given a diagnosis of a severe affective or psychotic disorder, thereby producing secondary inequities in ECT referral. Increasing the use of gold-standard treatment algorithms when considering ECT for patients of color is contingent on clinicians transcending the limitations posed by aversive racism to develop culturally unbiased, clinically indicated diagnostic and treatment rationales.

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.