Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report.

BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. METHODS: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). RESULTS: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. CONCLUSIONS: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03887715.

Bilateral rTMS Shows No Advantage in Depression nor in Comorbid Depression and Anxiety: A Naturalistic Study.

The objective was to determine if adding low-frequency right-sided rTMS treatment to the standard high-frequency left-sided treatment (LUL), referred to as sequential bilateral treatment (SBT), confers additional benefit for depression or anxiety outcomes. A retrospective chart review from January 2015 through December 2018 yielded 275 patients, all of whom were treated with a figure-8 coil for a major depressive episode. Their protocol was either LUL or SBL. Outcome measures were the Generalized Anxiety Disorder 7-item scale (GAD-7) and the Patient Health Questionnaire (PHQ-9). There was no significant difference in GAD-7 change scores between patients who had LUL or SBL (4.2 vs 4.8). This was also true when the sample was restricted to only patients who started with high GAD-7 scores. There was likewise no significant difference in PHQ-9 change scores between patients who had LUL or SBL (6.8 vs 5.1). Patients switching from LUL to SBL mid-course had poorer overall outcomes as compared to patients who stayed with the same protocol throughout treatment. This large naturalistic study shows no advantage for SBL treatment any group or condition examined. The results of this study have clinical applicability and sound a cautionary note regarding the use of combination rTMS protocols.

Could bipolar depressed patients respond better to rTMS than unipolar depressed patients? A naturalistic, observational study.

Previous studies of rTMS for bipolar depressed (BD) patients have yielded mixed results. In this retrospective, naturalistic, observational study, we reviewed charts of 317 patients undergoing rTMS treatment between 1/2015-2/2018, yielding 283 unipolar depressed (UD) and 34 BD patients. All were treated with a figure-of-8 coil, with either high-frequency (HF) left-sided, sequential bilateral (HF left-sided and low-frequency right-sided), or mixed protocols (switched from unilateral to bilateral mid-course).  Outcomes were the Generalized Anxiety Disorder scale (GAD-7) and Patient Health Questionnaire (PHQ-9). Total number of treatments and initial PHQ-9 scores did not differ between groups. BD patients had greater PHQ-9 change by treatment conclusion than UD patients. GAD-7 changes showed no between-group differences overall. PHQ-9 changes differences between groups were only seen with unilateral treatment, not with bilateral or mixed protocols. Unilateral treatment resulted in 45% remission (9/20) for BD patients vs. 15% (24/160) for UD patients by treatment end. Response was seen in 80% (16/20) of the unilaterally-treated BD patients vs. 39% (62/160) in UD patients. Regression analyses within BD patients found that unilateral treatment, use of non-lithium mood stabilizers, male sex, and number of treatments predicted PHQ-9 improvement.

Proceedings of the Sleep and Epilepsy Workgroup: Section 2 Comorbidities: Sleep Related Comorbidities of Epilepsy.

Epilepsy is a chronic disease with multiple, complex comorbidities. Bidirectional relationships exist among seizures, sleep, circadian rhythms, and diseases within and outside of the central nervous system. Seizures fragment sleep and can contribute to development of sleep disorders, which in turn leads to worse overall health and more seizures. Moreover, treatment options are often limited by interactions with anti-seizure medications. Advances in the fields of epilepsy and in sleep medicine have been made separately, and therefore treating patients with these comorbidities necessitates interdisciplinary approach. The focus of this section of the Sleep and Epilepsy Workgroup was to identify methods of collaboration and outline investigational, educational, and treatment priorities to mutually advance what we consider a combined field.

Sleep in psychogenic nonepileptic seizures and related disorders.

Psychogenic nonepileptic seizures (PNES), a form of functional neurological symptom disorder (FNSD), are very rarely seen in genuine, electroencephalography (EEG)-confirmed sleep. However, they are more commonly reported as a nocturnal occurrence, likely from a state that is misidentified as sleep (termed by some as "pseudosleep"). Sleep state can be helpful to distinguish FNSD from other neurological disorders. Pseudo-cataplexy, a form of "psychogenic" narcolepsy, "pseudo-parasomnia" and PNES can have a similar presentation. PNES and posttraumatic stress disorder (PTSD) frequently share previously experienced psychological trauma, and therefore the sleep abnormalities found in PTSD may be similarly present in PNES. Future research should use EEG monitoring to evaluate the sleep physiology of patients with FNSD such as PNES, as insights into sleep abnormalities may enable further understanding of the etiology and manifestations of PNES.

The degree of charge transfer in ground and charge-separated states revealed by ultrafast visible pump/mid-IR probe spectroscopy.

We demonstrate a new femtosecond visible pump/mid-IR probe spectroscopic approach to assess directly the ground- and excited-state degrees of charge transfer (CT) in donor-spacer-acceptor (D-Sp-A) structures. Two classes of (porphinato)zinc(II) (PZn)-based D-Sp-A compounds with either quinonyl (Q) or N-(N'-octyl)pyromellitic diimide (PI) electron acceptors were interrogated. Carbonyl antisymmetric stretching mode frequency domain transient-IR spectra of these species were recorded and analyzed for the Q/PI moieties. These data show that the acceptor mode frequency shift, DeltanuA, determined by this method provides a more accurate measure of the degree of CT in ground and charge-separated states relative to other techniques which rely on the ground-state frequency shift alone. This approach enables determination of new experimental benchmarks to test the power of complimentary computational methods and provides a means to probe the degree of CT in transitions that either overlap strongly with other bands or possess low oscillator strength.

Ultrasonographic screening in infants with isolated spinal strawberry nevi.

OBJECT: The authors performed spinal ultrasonography and/or magnetic resonance (MR) imaging in 20 consecutive newborns with spinal strawberry nevi. METHODS: In 15 patients the strawberry nevi were isolated and in five they were associated with other cutaneous markers of occult spinal dysraphism (OSD). In four of five patients with additional cutaneous markers, but in none of those without, MR imaging and surgical exploration demonstrated OSD. The authors found that strawberry nevi in isolation do not appear to indicate underlying dysraphic states. The sparse clinical literature on this topic, which is reviewed, confirms an association between OSD and strawberry nevi presenting in conjunction with other cutaneous signatures. By contrast, spinal strawberry nevi occurring alone may not indicate the presence of underlying dysraphism. CONCLUSIONS: A prospective study of larger numbers of patients with isolated strawberry nevi, undergoing MR imaging evaluation, is necessary to determine whether neuroimaging screening in these patients is indicated.