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).

A Pilot, Randomized Clinical Trial of Bedtime Doses of Prazosin Versus Placebo in Suicidal Posttraumatic Stress Disorder Patients With Nightmares.

PURPOSE/BACKGROUND: Observational studies show an association between nightmares and suicide. Prazosin is proposed as a nightmare treatment. This pilot, randomized clinical trial tested whether treatment of nightmares with prazosin would reduce suicidal ideas in suicidal posttraumatic stress disorder (PTSD) patients. METHODS/PROCEDURES: Twenty adult, suicidal PTSD patients with nightmares were blindly and randomly assigned 1:1 to escalating doses of prazosin versus placebo at bedtime only for 8 weeks. All participants had comorbid mood disorders and received stable doses of mood disorder medication. Outcomes of interest were measured weekly and included severity of suicidal ideation, nightmares, PTSD, insomnia, and depression. Longitudinal mixed-effects models assessed change in outcomes over time. FINDINGS/RESULTS: All psychometric measures improved over 8 weeks. However, nighttime measures of nightmares and insomnia showed significantly less improvement in the prazosin group, whereas there was no significant change in daytime measures of suicidal ideation and daytime-only PTSD symptoms. Two patients required emergency psychiatric hospitalization, but there were no suicide attempts and no deaths. IMPLICATIONS/CONCLUSIONS: This study confirmed an effect of nighttime-only prazosin on nighttime symptoms of insomnia and nightmares in suicidal PTSD patients who are experiencing nightmares. Surprisingly, the effect was in the direction opposite of what we expected. Furthermore, prazosin showed no signal on daytime measures including suicidal ideation. The results do not support a larger study of nighttime-only prazosin in suicidal PTSD patients but leave open the possibility of benefit from daytime administration of prazosin.

A multi-site randomized clinical trial to reduce suicidal ideation in suicidal adult outpatients with Major Depressive Disorder: Development of a methodology to enhance safety.

BACKGROUND/AIMS: Suicide is a major public health concern, yet there are very few randomized clinical trials that have been conducted to reduce suicidal ideation in patients at risk of suicide. We describe the rationale and refinements of such a trial that is designed to assess the effect of a hypnotic medication on suicidal ideation in adult outpatients currently experiencing suicidal ideation. METHODS: "Reducing Suicidal Ideation Through Insomnia Treatment" is a multi-site randomized clinical trial that includes three recruiting sites and one data management site. This 4-year study is in its second year of recruitment. The purpose of the study is to compare hypnotic medication versus placebo as an add-on treatment to a selective serotonin reuptake inhibitor as a means of reducing suicidal ideation in depressed adult outpatients with insomnia and suicidal ideation. The safety features of the study follow the 2001 National Institutes of Health guidelines for studies that include patients at risk of suicide. RESULTS: In total, 584 potential participants have undergone telephone screening; 67% of these failed the phone screen, most often due to an absence of expressed suicidal ideation (26% of the telephone screen fails). A total of 115 people appeared for a face-to-face baseline assessment, and 40 of these had completed a taper off of their ineffective psychotropic medications before the baseline assessments. In all, 64% of those who completed baseline assessments failed to proceed to randomization, most commonly because of no clinically significant suicidal ideation (51% of those excluded at baseline). One participant was offered and accepted voluntary psychiatric hospitalization in lieu of study participation. Thus far, 40 participants have been randomized into the study and 88.7% of scheduled visits have been attended, with 93.8% adherence to the selective serotonin reuptake inhibitor and 91.6% adherence to the randomized hypnotic versus placebo. None of the randomized participants have required hospitalization or had a suicide attempt. CONCLUSION: By carefully considering the inclusion and exclusion criteria and other safety features, the safe conduct of randomized clinical trials in suicidal adult patients is possible, including the inclusion of participants who have undergone a prescribed tapering off of psychotropic medications prior to baseline assessment.

Insomnia and the effect of zolpidem-extended-release on the sleep items of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia, and suicidal ideation: Relationship to patient age.

BACKGROUND: There are limited data regarding gamma-aminobutyric acid (GABA) allosteric modulator sleep-aid medications in persons with depression, insomnia, and suicidal ideation (SI). AIMS: This secondary analysis examined the relationship of age to insomnia and the impact of age on the treatment of insomnia with zolpidem extended-release (zolpidem-ER) in depressed suicidal patients. A prior report found that the addition of zolpidem-ER promoted significantly superior reductions in global severity of insomnia in depressed outpatients with insomnia and SI over 8 weeks, but here we report the differences among early, middle, and late insomnia. METHODS: This secondary analysis examined the three early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD) and their relationship to age and responsiveness to treatment with zolpidem-ER. One hundred and three patients with major depression, SI, and insomnia received open-label serotonin reuptake inhibitors and were randomly allocated 1:1 to receive zolpidem-ER or placebo at bedtime. Results: Older age at baseline was associated with worse middle and late insomnia, but not with early insomnia. Subsequent treatment with zolpidem-ER produced superior improvement in early and middle insomnia, but not late insomnia. CONCLUSIONS: These findings are consistent with the known age-related advancement of sleep timing in the general population and depressed outpatients and with the expected effects of a short half-life GABA allosteric modulator sleep aid. By implication, prescribers of pharmacologic treatment of insomnia in depressed patients should consider an alternative to zolpidem-ER when late insomnia is a concern.Trial registration number: ClinicalTrials.gov Identifier: NCT01689909.

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.

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.

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.

Double-Blinded Randomized Pilot Clinical Trial Comparing Cognitive Side Effects of Standard Ultra-Brief Right Unilateral ECT to 0.5 A Low Amplitude Seizure Therapy (LAP-ST).

BACKGROUND: Concerns over cognitive side effects (CSE) of electroconvulsive therapy (ECT) still limit its broader usage for treatment-resistant depression (TRD). The objectives of this study were to (1) examine the CSE of Low Amplitude Seizure Therapy (LAP-ST) at 0.5 A compared to Ultra-brief Right Unilateral (UB-RUL) ECT using Time to Reorientation (TRO) as the main acute primary outcome, and (2) to compare effects on depressive symptoms between the two treatment groups. METHODS: Participants were referred for ECT, consented for the study, and were randomized to a course of LAP-ST or standard UB-RUL ECT. TRO and depression were measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Eleven patients consented. Of these, eight with a current major depressive episode (MDE) of unipolar or bipolar disorders were randomized. TRO was faster for the LAP-ST (mean = 6.8 min; SE = 4.9) than standard RUL ECT (mean = 15.5 min; SE = 6.5). Depression improved similarly in the two arms of the study from baseline (MADRS: LAP-ST = 41.0; SE = 2.0, RUL = 39.0; SE = 3.8) to endpoint (MADRS score: LAP-ST = 8.0; SE7.2, RUL = 9.5; SE = 3.8). CONCLUSIONS: This pilot, randomized and blinded clinical trial, suggests that the LAP-ST (at 0.5 A) has faster reorientation and possibly lower CSE compared to standard RUL-UB ECT. Caution is advised in interpreting these results due to the small sample size of this pilot study. Thus, future studies with similar design are warranted for replicating these findings.

A two-site, open-label, non-randomized trial comparing Focal Electrically-Administered Seizure Therapy (FEAST) and right unilateral ultrabrief pulse electroconvulsive therapy (RUL-UBP ECT).

BACKGROUND: Focal Electrically-Administered Seizure Therapy (FEAST) is a form of electroconvulsive therapy (ECT) that spatially focuses the electrical stimulus to initiate seizure activity in right prefrontal cortex. Two open-label non-comparative studies suggested that FEAST has reduced cognitive side effects when compared to historical data from other forms of ECT. In two different ECT clinics, we compared the efficacy and cognitive side effects of FEAST and Right Unilateral Ultrabrief Pulse (RUL-UBP) ECT. METHODS: Using a non-randomized, open-label design, 39 depressed adults were recruited after referral for ECT. Twenty patients received FEAST (14 women; age 45.2 ± 12.7), and 19 received RUL-UBP ECT (16 women; age 43.2 ± 16.4). Key cognitive outcome measures were the postictal time to reorientation and the Columbia University Autobiographical Memory Interview: Short-Form (CUAMI-SF). Antidepressant effects were assessed using the Hamilton Rating Scale for Depression (HRSD24). RESULTS: In the Intent-to-treat sample, a repeated measures mixed model suggested no between group difference in HRSD24 score over time (F1,35 = 0.82, p = 0.37), while the response rate favored FEAST (FEAST: 65%; RUL-UBP ECT: 57.9%), and the remission rate favored RUL-UBP ECT (FEAST: 35%; RUL-UBP ECT: 47.4%). The FEAST group had numeric superiority in average time to reorientation (FEAST: 6.6 ± 5.0 min; RUL-UBP ECT: 8.8 ± 5.8 min; Cohens d = 0.41), and CUAMI-SF consistency score (FEAST: 69.2 ± 14.2%; RUL-UBP ECT: 63.9 ± 9.9%; Cohens d = 0.43); findings that failed to meet statistical significance. CONCLUSIONS: FEAST exerts similar efficacy relative to an optimal form of conventional ECT and may have milder cognitive side effects. A blinded, randomized, non-inferiority trial is needed.

Bedtime doses of prazosin do not affect daytime salivary amylase markers in PTSD.

Overactivity of the noradrenergic (NE) system within the central nervous system (CNS) has been postulated as a key pathophysiology of posttraumatic stress disorder (PTSD). The activity of the enzyme salivary α-amylase (sAA) has been proposed as an indirect measure of CNS NE activity, and sAA is elevated in PTSD. As an antagonist of the α-1 NE receptor, prazosin would be expected to alter sAA values in PTSD patients. However, given its short half-life, it is not clear whether bedtime doses would have an effect on daytime sAA. In the present study, we assayed daytime sAA in 20 suicidal PTSD patients who were randomized to prazosin versus placebo at bedtime-only, and found no effect in daytime sAA. These findings are consistent with studies showing an advantage for twice daily dosing of prazosin in PTSD.

Magnitude of Reduction and Speed of Remission of Suicidality for Low Amplitude Seizure Therapy (LAP-ST) Compared to Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial.

Background: Although treatment guidelines support use of electroconvulsive therapy (ECT) for acute suicidality, it is associated with cognitive side effects. The effect of Low Amplitude Seizure Therapy (LAP-ST) on suicidality is unknown. Our prior precision LAP-ST (pLAP-ST) performing titrating in the current domain has provided initial proof of concept data in humans of its advantage in terms of reduction of cognitive side effects. The aims of this report are to: 1) compare LAP-ST (at 500mA) versus standard Right Unilateral (RUL) ECT (at 900 mA) in terms of magnitude of remission of suicidality in a randomized allocation and 2) compare the speed of remission of suicidality between LAP-ST versus RUL ECT. Methods: Patients were randomized to either LAP-ST or RUL ECT. The scores pertaining to the suicidal ideation (SI) item on the Montgomery-Åsberg Depression Rating Scale (MADRS) were analyzed using descriptive analysis and no confirmatory statistical analysis was performed due to a priori sample size limitations for this pilot study. SI item remission was defined as 2 or below on this item. Results: Eleven patients with major depressive episode (MDE) of mainly unipolar or bipolar disorders signed consent. Of these, 7 were eligible and were randomized and included in the analysis; all were actively suicidal at baseline (suicide item above 2), except 1 patient who had suicide item at 2 in the RUL ECT group. Suicidality remitted on average by session 3 and remission occurred for all patients by session 4. The SI mean score improvement from baseline to endpoint for LAP-ST was 5.1 and for RUL ECT was 3.0. Conclusions: LAP-ST has larger effect size and speed of remission of suicidality compared to standard RUL ECT. Future studies are warranted for replicating these findings. (ClinicalTrials.gov ID: NCT02583490).

Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT): A Randomized Clinical Trial.

OBJECTIVE: The authors sought to determine whether targeted treatment of insomnia with controlled-release zolpidem (zolpidem-CR) in suicidal adults with insomnia would provide a reduction in suicidal ideation superior to placebo. METHODS: Reducing Suicidal Ideation Through Insomnia Treatment was an 8-week three-site double-blind placebo-controlled parallel-group randomized controlled trial of zolpidem-CR hypnotic therapy compared with placebo, in conjunction with an open-label selective serotonin reuptake inhibitor. Participants were medication-free 18- to 65-year-olds with major depressive disorder, insomnia, and suicidal ideation. Suicidal ideation was the main outcome, measured first by the Scale for Suicide Ideation and second by the Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: A total of 103 participants were randomly assigned to receive zolpidem-CR (N=51) or placebo (N=52) (64 women and 39 men; mean age=40.5 years). Zolpidem-CR had a robust anti-insomnia effect, especially in patients with the most severe insomnia symptoms. No significant treatment effect was observed on the Scale for Suicide Ideation (least squares mean estimate=-0.56, SE=0.83, 95% CI=-2.19, 1.08), but the reduction in scores was significantly positively related to improvement in insomnia after accounting for the effect of other depression symptoms. The C-SSRS indicated that zolpidem-CR had a significant treatment effect (least squares mean estimate=-0.26, SE=0.12, 95% CI=-0.50, -0.02). The advantage for zolpidem-CR in reducing suicidal ideation on the C-SSRS was greater in patients with more severe insomnia. No deaths or suicide attempts occurred. CONCLUSIONS: Although the results do not support the routine prescription of hypnotic medication for mitigating suicidal ideation in all depressed outpatients with insomnia, they suggest that coprescription of a hypnotic during initiation of an antidepressant may be beneficial in suicidal outpatients, especially in patients with severe insomnia.

Effects of continuation electroconvulsive therapy on quality of life in elderly depressed patients: A randomized clinical trial.

We examined whether electroconvulsive therapy (ECT) plus medications ("STABLE + PHARM" group) had superior HRQOL compared with medications alone ("PHARM" group) as continuation strategy after successful acute right unilateral ECT for major depressive disorder (MDD). We hypothesized that scores from the Medical Outcomes Study Short Form-36 (SF-36) would be higher during continuation treatment in the "STABLE + PHARM" group versus the "PHARM" group. The overall study design was called "Prolonging Remission in Depressed Elderly" (PRIDE). Remitters to the acute course of ECT were re-consented to enter a 6 month RCT of "STABLE + PHARM" versus "PHARM". Measures of depressive symptoms and cognitive function were completed by blind raters; SF-36 measurements were patient self-report every 4 weeks. Participants were 120 patients >60 years old. Patients with dementia, schizophrenia, bipolar disorder, or substance abuse were excluded. The "PHARM" group received venlafaxine and lithium. The "STABLE + PHARM" received the same medications, plus 4 weekly outpatient ECT sessions, with additional ECT session as needed. Participants were mostly female (61.7%) with a mean age of 70.5 ± 7.2 years. "STABLE + PHARM" patients received 4.5 ± 2.5 ECT sessions during Phase 2. "STABLE + PHARM" group had 7 point advantage (3.5-10.4, 95% CI) for Physical Component Score of SF-36 (P < 0.0001), and 8.2 point advantage (4.2-12.2, 95% CI) for Mental Component Score (P < 0.0001). Additional ECT resulted in overall net health benefit. Consideration should be given to administration of additional ECT to prevent relapse during the continuation phase of treatment of MDD. CLINICAL TRIALS.GOV: NCT01028508.

Effects of a Course of Right Unilateral Ultrabrief Pulse Electroconvulsive Therapy Combined With Venlafaxine on Insomnia Symptoms in Elderly Depressed Patients.

OBJECTIVE: Antidepressant medications have a variety of effects on sleep, apart from their antidepressant effects. It is unknown whether electroconvulsive therapy (ECT) has effects on perceived sleep in depressed patients. This secondary analysis examines the effects of ECT on perceived sleep, separate from its antidepressant effects. METHODS: Elderly patients with major depressive disorder, as defined by DSM-IV, received open-label high-dose, right unilateral ultrabrief pulse ECT, combined with venlafaxine, as part of participating in phase 1 of the National Institute of Mental Health-supported study Prolonging Remission in Depressed Elderly (PRIDE). Phase 1 of PRIDE participant enrollment period extended from February 2009 to August 2014. Depression severity was measured with the Hamilton Depression Rating Scale-24 item (HDRS24), and measures of insomnia severity were extracted from the HDRS24. Participants were characterized at baseline as either "high-insomnia" or "low-insomnia" subtypes, based upon the sum of the 3 HDRS24 sleep items as either 4-6 or 0-3, respectively. Insomnia scores were followed during ECT and were adjusted for the sum of all the HDRS24 non-sleep items. Generalized linear models were used for longitudinal analysis of insomnia scores. RESULTS: Two hundred forty patients participated, with 48.3% in the high-insomnia and 51.7% in the low-insomnia group. Although there was a reduction in the insomnia scores in the high-insomnia group, only 12.4% of them experienced remission of insomnia after a course of ECT, despite an increase in utilization of sleep aids across the course of ECT, from 8.6% to 23.2%. The degree of improvement in insomnia symptoms paralleled the degree of improvement in non-insomnia symptoms. A "low" amount of improvement on the sum of the HDRS non-insomnia items (HDRS-sleep) was accompanied by a "low" amount of improvement in insomnia scores (change of -1.6 ± 1.2, P < .0001), while a "high" amount of improvement on the sum of the HDRS non-insomnia items was accompanied by a "higher" amount of improvement in insomnia scores (change of -3.1 ± 1.6, P < .0001). After adjustment for non-insomnia symptoms, there was no change in insomnia in the low-insomnia group. CONCLUSIONS: We found that ECT, combined with venlafaxine, has a modest anti-insomnia effect that is linked to its antidepressant effect. Most patients will have some degree of residual insomnia after ECT, and will require some consideration of whether additional, targeted assessment and treatment of insomnia is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01028508.

Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.

OBJECTIVE: Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. METHOD: This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. RESULTS: Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. CONCLUSIONS: The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.

Effects of a right unilateral ultrabrief pulse electroconvulsive therapy course on health related quality of life in elderly depressed patients.

INTRODUCTION: Patients with Major Depressive Disorder (MDD) referred for electroconvulsive therapy (ECT) have poorer Health Related Quality of Life (HRQOL), compared with other patients with MDD, but ECT is associated with significant and durable improvement in HRQOL. However, no prior research has focused exclusively on elderly patients with MDD receiving ECT. METHODS: HRQOL data from 240 depressed patients over the age of 60 was measured with the Medical Outcomes Study Short Form 36 (SF-36). The SF-36 was measured before and after a course of acute ECT. Predictors of change in HRQOL scores were identified by generalized linear modeling. RESULTS: At baseline, participants showed very poor HRQOL. After treatment with ECT, the full sample showed marked and significant improvement across all SF-36 measures, with the largest gains seen in dimensions of mental health. Across all participants, the Physical Component Summary (PCS) score improved by 2.1 standardized points (95% CI, 0.61,3.56), while the Mental Component Summary (MCS) score improved by 12.5 points (95% CI, 7.2,10.8) Compared with non-remitters, remitters showed a trend toward greater improvement in the PCS summary score of 2.7 points (95%CI, -0.45, 5.9), while the improvement in the MCS summary score was significantly greater (8.5 points, 95% CI, 4.6,12.3) in the remitters than non-remitters. Post-ECT SF-36 measurements were consistently and positively related to baseline scores and remitter/non-remitter status or change in depression severity from baseline. Objective measures of cognitive function had no significant relationships to changes in SF-36 scores. LIMITATIONS: This study's limitations include that it was an open label study with no comparison group, and generalizability is limited to elderly patients. DISCUSSION: ECT providers and elderly patients with MDD treated with ECT can be confident that ECT will result in improved HRQOL in the short-term. Attaining remission is a key factor in the improvement of HRQOL. Acute changes in select cognitive functions were outweighed by improvement in depressive symptoms in determining the short term HRQOL of the participants treated with ECT.

Reduced pulmonary endothelium-bound angiotensin converting enzyme activity in diabetic rabbits.

We examined the effects of diabetes on pulmonary capillary endothelial cell (EC) function in diabetic rabbits. One, three and six weeks after alloxan treatment, rabbits were anesthetized and pulmonary endothelium-bound angiotensin converting enzyme (ACE) activity was estimated from the single-pass transpulmonary hydrolysis of benzoyl-Phe-Ala-Pro (BPAP), an ACE specific substrate. ACE activity significantly decreased in 1- and 3-week diabetic rabbits and returned to control levels at 6 weeks. Capillary dilation, parenchymal hemorrhage and erythrocyte clumping were maximal in 3-week diabetic rabbits. We conclude that in the alloxan-diabetic rabbit, there are transient functional and more persistent morphological alterations.

Asenapine-induced restless legs syndrome: differentiation from akathisia.

Akathisia and restless legs syndrome (RLS) share some common clinical features and a common relationship with dopamine dysfunction. However, the underlying causes and appropriate treatments for akathisia and RLS are different. Herein we describe a case of RLS that was precipitated by a single dose of asenapine, which is an atypical antipsychotic, and dissect the features that support the contention that this was indeed a case of RLS and not akathisia.

Knowledge of hereditary prostate cancer among high-risk African American men.

PURPOSE/OBJECTIVES: To measure knowledge of hereditary prostate cancer in a group of high-risk African American men. DESIGN: Cross-sectional, correlational pilot study. SETTING: Four geographic sites: Detroit, MI; Houston, TX; Chicago, IL; and Columbia, SC. SAMPLE: 79 men enrolled in the African American Hereditary Prostate Cancer Study. METHODS: Telephone interviews. MAIN RESEARCH VARIABLES: Knowledge of hereditary prostate cancer. FINDINGS: Knowledge of hereditary prostate cancer was low. CONCLUSIONS: The high percentage of incorrect responses on questions that measure genetic testing, prevention, and risk based on a positive family history highlights educational needs. IMPLICATIONS FOR NURSING: A critical need exists for nurses to educate high-risk African American men about hereditary prostate cancer.

beta-hydroxybutyrate induces acute pulmonary endothelial dysfunction in rabbits.

The authors examined the effects of high ketone body and glucose concentrations on endothelial cell (EC) function in perfused rabbit lungs. beta-Hydroxybutyrate (beta OHB), at 5 mM, decreased endothelial angiotensin-converting enzyme (eACE) activity, whereas 25 mM glucose (HG), 1 mM beta OHB, or 10 mM acetoacetate (AcAc) did not. Dry to wet weight ratios were also reduced in lungs perfused with 5 mM beta OHB, but not with AcAc. beta OHB, at 5 mM, caused massive hemorrhage and interstitial and alveolar neutrophil infiltration; AcAc only produced engorgement of septal capillaries. Thus, pulmonary EC dysfunction occurs in rabbit lungs acutely perfused with beta OHB, but not with AcAc or glucose.