Vagus nerve stimulation: An update on a novel treatment for treatment-resistant depression.

In this review, we provide an overview of essential clinical trials examining the effect of vagal nerve stimulation (VNS) in treatment-resistant depression (TRD), the applicable neuroanatomy of the vagus nerve, and the proposed mechanism of action (MOA) of VNS in TRD. Vagal nerve stimulation (VNS) is currently the only FDA-approved neurostimulation treatment for severe treatment-resistant depression (TRD). The implanted VNS device sends electrical impulses to the left cervical vagus nerve, resulting in stimulation of afferent vagal brainstem pathways known to be associated with mood regulation. Within the last decade, several clinical trials have attempted to further elucidate this effect specifically in TRD. Early clinical trials including the D01, D02, and D03 trials showed promising evidence of the antidepressant efficacy and durability of VNS as a treatment for TRD. Later trials comparing VNS and treatment-as-usual (TAU) resulted in similar findings regarding antidepressant efficacy and durability. VNS was additionally found to be beneficial in improving quality of life and suicidality among unipolar TRD patients and depression among bipolar TRD patients. Ongoing and future studies such as the RECOVER trial continue to investigate the psychiatric benefits of VNS within the TRD population. Although the MOA of VNS in TRD is still not fully understood, recent brain imaging studies and animal studies have proven instrumental in addressing this knowledge gap.

Enhancing Cognition in Older Persons with Depression or Anxiety with a Combination of Mindfulness-Based Stress Reduction (MBSR) and Transcranial Direct Current Stimulation (tDCS): Results of a Pilot Randomized Clinical Trial.

Objectives: Individuals with subjective memory complaints and symptoms of depression and/or anxiety are at high risk for further cognitive decline, and possible progression to dementia. Low-burden interventions to help slow or prevent cognitive decline in this high-risk group are needed. The objective of this study is to assess the feasibility of combining Mindfulness-Based Stress Reduction (MBSR) with transcranial direct current stimulation (tDCS) to increase putative benefits of MBSR for cognitive function and everyday mindfulness in depressed or anxious older adults with subjective cognitive decline. Methods: We conducted a two-site pilot double-blind randomized sham-controlled trial, combining active MBSR with either active or sham tDCS. The intervention included weekly in-class group sessions at the local university hospital and daily at-home practice. Anodal tDCS was applied for 30 min during MBSR meditative practice, both in-class and at-home. Results: Twenty-six individuals with subjective cognitive complaints and symptoms of depression and/or anxiety were randomized to active (n = 12) or sham tDCS (n = 14). The combination of MBSR and tDCS was safe and well tolerated, though at-home adherence and in-class attendance were variable. While they were not statistically significant, the largest effect sizes for active vs. sham tDCS were for everyday mindfulness (d = 0.6) and social functioning (d = 0.9) (F (1,21) = 3.68, p = 0.07 and F (1,21) = 3.9, p = 0.06, respectively). Conclusions: Our findings suggest that it is feasible and safe to combine tDCS with MBSR in older depressed and anxious adults, including during remote, at-home use. Furthermore, tDCS may enhance MBSR via transferring its meditative learning and practice into increases in everyday mindfulness. Future studies need to improve adherence to MBSR with tDCS. Trial Registration: ClinicalTrials.gov (NCT03653351 and NCT03680664). Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-021-01764-9.

iTBS to Relieve Depression and Executive Dysfunction in Older Adults: An Open Label Study.

BACKGROUND: Executive Function Deficits (EFD) accompany depression and are associated with poor outcomes in older adults. We examined whether Intermittent Theta Burst Stimulation (iTBS) could improve depression with EFD. METHODS: Thirteen geriatric patients with depression and EFD were enrolled. Open label iTBS was delivered bilaterally over the dorso-lateral-prefrontal-cortex for four weeks. RESULTS: Montgomery Asberg Depression Scale scores improved significantly from baseline to treatment-end, mean change in score = 11.82 points, 95% CI = 8.3, 15.4. The Flanker Inhibitory control and attention test showed significant improvement in executive function from baseline to treatment-end, mean change in score = -7.73, 95% CI ( -13.54, -1.92). Side effects included twitching in facial muscles (n = 11), headaches (n = 10) and stimulation discomfort (n = 4). LIMITATIONS: Small sample size and lack of a sham comparator. CONCLUSION: iTBS improved depression with EFD in older adults. Side effects appeared higher than in previous iTBS studies.

A Novel Deletion in the RPL5 Gene in a Lebanese Child With Diamond Blackfan Anemia Unresponsive to Steroid Treatment.

Diamond-Blackfan Anemia (DBA) is a rare inherited form of pure red cell aplasia that usually manifests in infancy or early childhood, and is characterized by normochromic macrocytic anemia and bone marrow erythroblastopenia. The majority of DBA cases are associated with mutations in ribosomal protein genes. Here, we describe a Lebanese girl with RPL5-mutated DBA unresponsive to steroid treatment who died from complications following late hematopoietic stem cell transplantation performed at the age of 15 years.