Search

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. McCall reports royalties from Wolters Kluwer and payments from Carelon and Idorsia as a scientific advisor. Dr. Krystal reports consultancy to Axsome Therapeutics, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage, Takeda. Research support from Janssen Pharmaceuticals, Axsome Pharmaceutics, Attune, Harmony, Neurocrine Biosciences, Reveal Biosensors, The Ray and Dagmar Dolby Family Fund, and the National Institutes of Health. Stock options from Neurawell, Big-Health. Dr. Benca reports consultancy to Eisai, Idorsia, Genentech, Jazz, Merck, and Sage. Research support from Eisai.

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., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Published by Elsevier Inc.)

Introduction: Progress reducing suicide death will require randomized clinical trials (RCTs) specifically targeting suicide risk. Even large RCTs may not stipulate suicide death as the primary outcome, as suicide death is relatively uncommon. Therefore, RCTs may need to specify suicidal ideation as a proxy indicator of risk. There is no consensus on the best tool for measuring suicidal ideation within RCTs. We contrasted the psychometric performance of three suicidal ideation measures to address this need., Methods: We applied item response theory to the Beck Scale for Suicide Ideation (BSSI), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the suicide item of the Hamilton Rating Scale for Depression (HRSD) for 101 outpatients with depression and suicidal ideation participating in a RCT with suicidal ideation as the primary outcome., Results: All measures of suicidal ideation were equally able to detect low and very high levels of suicidal ideation., Conclusions: The choice of the specific measure of suicidal ideation in a clinical trial may be dictated by time and financial resources versus the need for granularity in the interpretation of the scores., (© 2021 The American Association of Suicidology.)

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., Competing Interests: Supported in part by an unrestricted educational grant from the MECTA Corporation. The MECTA Corporation also provided custom-modified MECTA spECTrum 5000Q devices for the delivery of FEAST. The MECTA was not involved in study design, data analysis, or data interpretation. N.A.Y. received research support from Department of Veteran Affairs, Augusta Biomedical Research Corporation, MECTA Corporation, and Merck (but not salary support). N.A.Y. also received Speaker CME honoraria from the Georgia Department of Behavioral Health and Developmental Disabilities and Psychiatric Annals for unrelated CME topics. W.V.M. receives research support from MECTA, Vistagen, and Merck. W.V.M. receives royalties from Wolters Kluwer and is a scientific adviser for Jazz, Sage, and Janssen Pharmaceuticals. H.A.S. is the inventor on a patent for FEAST (US8712532 B2), titration in the current domain in electroconvulsive therapy (US9789310), and the adjustment of current in electroconvulsive therapy devices (US10583288), each held by the MECTA Corporation. H.A.S. is also the originator of magnetic seizure therapy and serves as a consultant to the MECTA Corporation, Neuronetics, Inc, and LivaNova LPC. The other authors have no conflicts of interest or financial disclosures to report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2020 John Wiley & Sons Ltd.)

Background: Electroconvulsive therapy (ECT) is usually reserved for treatment of severe major depressive disorder (MDD), but may be equally effective in the treatment of moderate-severity MDD. This possibility, however, has only been studied to a very limited extent. We therefore investigated the efficacy of ECT after stratifying patients into severe MDD and moderate-severity MDD., Methods: We used data from the Prolonging Remission in Depressed Elderly (PRIDE) study, in which 240 patients (≥60 years) with MDD were treated with right unilateral ultrabrief pulse ECT, combined with venlafaxine. We used the six-item core depression subscale (HAM-D 6 ) of the Hamilton Depression Rating Scale to define depression severity. Participants with baseline total scores ≥12 on the HAM-D 6 were considered to have severe MDD, while those with HAM-D 6 total scores <12 were considered to have moderate-severity MDD., Results: Among the participants with severe MDD and moderate-severity MDD, the mean change in the HAM-D 6 total score from baseline to endpoint was -8.2 (95% confidence interval (95%CI) = -7.5; -9.0, paired t-test: p < 0.001) and -5.9 (95%CI = -5.1; -6.6, paired t-test: p < 0.001), respectively. A total of 63% of those with severe MDD and 75% of those with moderate-severity MDD achieved remission (HAM-D 6 total score ≤4) (Pearson's 2-sample chi-squared test of difference between groups: p = 0.27)., Limitations: The PRIDE study was not designed to address this research question., Conclusions: ECT combined with venlafaxine appears to be an effective treatment for moderate-severity MDD. It may be appropriate to expand the indications for ECT to include patients with moderate-severity MDD., Competing Interests: Declaration of Competing Interest Dr. Østergaard and Dr. Speed report no conflicts of interest. Dr. Kellner has previously received grant support from the National Institute of Mental Health; he receives fees from UpToDate, Psychiatric Times and Northwell Health; he receives royalties from Cambridge University Press. Dr. McClintock has received research support from the National Institutes of Health and he is a consultant to Pearson. Dr. Husain reports research grant support from: the National Institute of Health, the National Institute of Mental Health, the National Institute of Drug Abuse, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the National Alliance for Research on Schizophrenia, Stanley Medical Foundation, Cyberonics, Neuronetics (past), and St. Jude Medical/Abbott. Dr. Petrides reports grants from the National Institute of Mental Health and support for clinical trials from St. Jude Medical, Alkermes, Lundbeck, Proteus, and the Stanley Foundation. Dr. McCall receives research support from MECTA Corp, Vistagen, Merck and PCORI, is a paid scientific advisor for Sage, Jazz, and Janssen pharmaceutical companies and receives royalties from Wolters Kluwer. Dr. Lisanby has received grant support from the Brain and Behavior Research Foundation, the Stanley Medical Research Foundation, Neosync, Nexstim, NIH, and Brainsway. The opinions expressed in this article are the author's own and do not reflect the views of the National Institutes of Health, the Department of Health and Human Services, or the United States government., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Electroconvulsive therapy (ECT) technique is often changed after insufficient improvement, yet there has been little research on switching strategies., Objective: To document clinical outcome in ECT nonresponders who were received a second course using high dose, brief pulse, bifrontotemporal (HD BP BL) ECT, and compare relapse rates and cognitive effects relative to patients who received only one ECT course and as a function of the type of ECT first received., Methods: Patients were classified as receiving Weak, Strong, or HD BP BL ECT during three randomized trials at Columbia University. Nonresponders received HD BP BL ECT. In a separate multi-site trial, Optimization of ECT, patients were randomized to right unilateral or BL ECT and nonresponders also received further treatment with HD BP BL ECT., Results: Remission rates with a second course of HD BP BL ECT were high in ECT nonresponders, approximately 60% and 40% in the Columbia University and Optimization of ECT studies, respectively. Clinical outcome was independent of the type of ECT first received. A second course with HD BP BL ECT resulted in greater retrograde amnesia immediately, two months, and six months following ECT., Conclusions: In the largest samples of ECT nonresponders studied to date, a second course of ECT had marked antidepressant effects. Since the therapeutic effects were independent of the technique first administered, it is possible that many patients may benefit simply from longer courses of ECT. Randomized trials are needed to determine whether, when, and how to change treatment technique in ECT., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

In this paper, we report the rate of previously undiagnosed obstructive sleep apnea (OSA) in a randomized clinical trial (RCT) of suicidal patients with major depressive disorder (MDD). One hundred and twenty-five suicidal adults with MDD were recruited into a RCT. None were suspected to have OSA. Fourteen percent met diagnostic criteria for OSA. The Apnea Hypopnea Index (AHI) was predicted by increasing age, male sex, and higher Body Mass Index. However, neither the degree of daytime sleepiness nor the degree of insomnia predicted AHI severity. A high degree of suspicion is warranted for OSA in suicidal patients with MDD, and for patients with treatment-resistant depression. ClinicalTrials.gov identifier: NCT01689909., (Copyright © 2019 Elsevier Ltd. All rights reserved.)