[Posted 1/Apr/2024]

AUDIENCE: Neurology, Internal Medicine

KEY FINDINGS: GPi-DBS increases metabolic activity at the stimulation site and sensorimotor network. The clinical benefit and adverse effects are mediated by modulation of specific networks.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a highly efficacious treatment for cervical dystonia, but its mechanism of action is not fully understood. Here, we investigate the brain metabolic effects of GPi-DBS in cervical dystonia.

DETAILS: Eleven patients with GPi-DBS underwent brain 18F-fluorodeoxyglucose positron emission tomography imaging during stimulation on and off. Changes in regional brain glucose metabolism were investigated at the active contact location and across the whole brain. Changes in motor symptom severity were quantified using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), executive function using trail making test (TMT) and parkinsonism using Unified Parkinson's Disease Rating Scale (UPDRS). The mean (SD) best therapeutic response to DBS during the treatment was 81 (22)%. The TWSTRS score was 3.2 (3.9) points lower DBS on compared with off (p=0.02). At the stimulation site, stimulation was associated with increased metabolism, which correlated with DBS stimulation amplitude (r=0.70, p=0.03) but not with changes in motor symptom severity (p>0.9). In the whole brain analysis, stimulation increased metabolism in the GPi, subthalamic nucleus, putamen, primary sensorimotor cortex (PFDR0.05). Acute improvement in TWSTRS correlated with metabolic activation in the sensorimotor cortex and overall treatment response in the supplementary motor area. Worsening of TMT-B score was associated with activation of the anterior cingulate cortex and parkinsonism with activation in the putamen.

Copyright © BMJ Publishing Group Ltd. All rights reserved.

Source: Honkanen E. A., Rönkä J., Pekkonen E., et al. (2024). GPi-DBS-Induced Brain Metabolic Activation in Cervical Dystonia. Journal of Neurology, Neurosurgery & Psychiatry. 2024; 95(4): 300-308. Published: April, 2024. DOI: 10.1136/jnnp-2023-331668.

A Randomized, Double-Blind, Placebo-Controlled Trial

[Posted 1/Jul/2026]

AUDIENCE: Psychiatry, Neurology

KEY FINDINGS: This randomized controlled trial provides the first evidence that a pharmacological intervention, buprenorphine, significantly sustains and enhances the antisuicidal effects of ketamine in MDD. These findings offer a potentially scalable and safe therapeutic option for a population at risk of suicide.

BACKGROUND: Ketamine rapidly reduces suicidal ideation in major depressive disorder (MDD), but its effects are transient. Preclinical and clinical studies suggest that ketamine’s antidepressant and antisuicidal effects may be partly mediated by mu-opioid receptor (MOR) modulation. The authors investigated the efficacy and safety of low-dose sublingual buprenorphine, a partial MOR agonist, as a follow-on treatment to prolong the effects of intravenous ketamine.

DETAILS: This was a randomized, double-blind, placebo-controlled trial conducted at a single outpatient center in the United States. Adults with MDD and a total score >=6 on the Scale for Suicide Ideation (SSI) were randomly assigned in a 1:1 ratio to receive either sublingual buprenorphine (0.2 to 0.8 mg/day) or a matched placebo for 4 weeks, beginning 48 hours after a single open-label intravenous ketamine infusion (0.5 mg/kg over 40 minutes). The primary outcome was the change in SSI total score, assessed weekly from day 1 through day 31. From November 2020 to March 2025, 50 participants (68% female) received ketamine, of whom 45 completed at least 1 week of follow-on treatment. Both groups showed significant reductions in SSI total scores, with greater improvement in the buprenorphine group (mean change, -11.6, SD=5.8; N=23) than the placebo group (mean change, -6.3, SD=7; N=22) (Glass delta=0.76, 95% CI=0.11, 1.39). Mixed-effects modeling showed a significant time-by-treatment interaction (p0.001). Depression scores did not differ significantly between groups. No serious treatment-related adverse events occurred.

Copyright © American Psychiatric Association. All rights reserved.

Source: Tucciarone, J. M., Bandeira, I. D., Blasey, C., et al. Low-Dose Buprenorphine Following Ketamine Treatment for Suicidal Ideation in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial. American Journal of Psychiatry. 2026; 183(6): 409-419. Published: June, 2026. DOI: 10.1176/appi.ajp.202508

[Posted 24/Jun/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS:

• FDA approved the first generic form of baloxavir marboxil tablets.
• Approved for patients aged 5 years and older.
• Indications include acute uncomplicated influenza treatment and post-exposure prophylaxis.
• Treatment eligibility requires symptom duration of no more than 48 hours.
• Contraindicated in patients with hypersensitivity to baloxavir marboxil or formulation ingredients.
• Common adverse effects: diarrhea, bronchitis, nausea, sinusitis, and headache.
• In the U.S., nine out of 10 prescriptions filled are for generic drugs.
• Approval granted to Norwich Pharmaceuticals, Inc.

BACKGROUND: The U.S. Food and Drug Administration (FDA) announced approval of the first generic version of baloxavir marboxil tablets, previously marketed as Xofluza. This approval introduces the first single-dose generic option for both treatment and post-exposure prophylaxis of influenza. The approval was issued ahead of the 2026–2027 influenza season with the objective of expanding access to generic medications and supporting public health preparedness.

DETAILS: Generic baloxavir marboxil tablets are approved for use in patients aged 5 years and older. Indications include treatment of acute uncomplicated influenza in individuals who have experienced symptoms for no more than 48 hours and who are either otherwise healthy or at elevated risk for influenza-related complications. The medication is also approved for post-exposure prophylaxis following contact with an infected individual.

The drug is contraindicated in patients with known hypersensitivity to baloxavir marboxil or any formulation components. Safety considerations include warnings regarding increased incidence of treatment-emergent resistance in patients younger than 5 years of age.

Common adverse effects reported include diarrhea, bronchitis, nausea, sinusitis, and headache.

FDA approval of generic baloxavir marboxil provides an additional therapeutic option for influenza management through a single-dose regimen. Increased availability of generic alternatives may support broader patient access and affordability while maintaining treatment availability before the upcoming flu season.

Copyright © Skyscape Editorial Team. All rights reserved.

Source: News Release: FDA Approves First Single-Dose Generic Treatment for Influenza.. FDA. Published: June 17, 2026.

Clinical Characteristics and Neurodevelopmental Outcomes in 30 Patients

[Posted 19/Jun/2026]

AUDIENCE: Neurology, Neonatology

KEY FINDINGS: KCNQ2-related neonatal epilepsy shows robust, topology-dependent genotype-phenotype correlations with prognostic utility: early EEG patterns flag risk; transmembrane missense variants are associated with DEE, whereas single-allele truncating/NMD variants are associated with SeL(F)NE. Apparent benefits of oxcarbazepine reflect associations in an observational cohort and should not be interpreted as causal; prospective, phenotype-stratified studies are warranted. Long-term developmental surveillance remains essential, particularly for individuals with DEE and those with severe early EEG patterns or variants in transmembrane/pore regions.

BACKGROUND: The aim of this study was to characterize clinical features, genetic architecture, treatment responses, and neurodevelopmental outcomes in neonatal epilepsy associated with KCNQ2 variants and to delineate genotype-phenotype correlations.

DETAILS: Authors conducted a retrospective, two-center study of 30 neonates from 2019 to 2024. All patients underwent whole-exome sequencing with Sanger confirmation and, at last follow-up, were classified, according to International League Against Epilepsy criteria as having self-limited (familial) neonatal epilepsy (SeL[F]NE) or developmental and epileptic encephalopathy (DEE). Primary outcomes were seizure freedom by 6 months and milestone-based three-level neurodevelopment (normal/mild/severe). Clinical/EEG/MRI features and variant class/topology were compared across phenotypes. Most infants presented in the first week of life (median 3 days), typically with focal tonic seizures. EEG abnormalities were common (90%); burst-suppression/profound discontinuity consistently signaled adverse neurodevelopment. MRI was often normal (53%) or nonspecific. Authors identified 29 distinct variants (32 occurrences) across 30 patients. Twenty-eight carried a single heterozygous variant, and 2 carried 2 heterozygous variants (phase not determined); missense variants predominated (21/30, 70%). Clear topology-phenotype patterns emerged: transmembrane missense variants—especially S5-pore-S6—were enriched in DEE, whereas C-terminal/nontransmembrane variants were associated with SeL(F)NE and benign outcomes. At the last follow-up, SeL(F)NE accounted for 63% and DEE 37%. Seizure freedom reached 93%. Oxcarbazepine was often associated with seizure control after phenobarbital nonresponse, but this observational signal should not be interpreted as causal. Neurodevelopment was normal in 63%; delays occurred only within the DEE cohort. All 5 single-allele truncating/NMD lesions (CNV deletion, canonical splice-site, 2 nonsense, 1 frameshift) aligned with SeL(F)NE, whereas the 2 individuals with 2 heterozygous variants were classified as DEE with marked impairment; however, phase was not determined and 1 recurrent variant (p.E515D) was classified as likely benign, precluding inference of 2 pathogenic alleles.

Copyright © American Academy of Neurology. All Rights Reserved.

Source: Li, Y., Li, J., Li, L., et al. KCNQ2 Variants in Neonatal Epilepsy: Clinical Characteristics and Neurodevelopmental Outcomes in 30 Patients. Neuro Genetics. 2026; 12(3): e200380. Published: June, 2026. 12(3): e200380. DOI: 10.1212/NXG.0000000000200380.

[Posted 15/Jun/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.

BACKGROUND: Influenza outbreaks in nursing homes (NHs) pose a substantial threat to older adults, often resulting in morbidity and mortality. The Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America (IDSA) recommend prompt postexposure prophylaxis, also termed chemoprophylaxis or prophylaxis with oseltamivir, for all residents who are not ill to limit influenza spread in NHs. Purpose of the study is to examine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days.

DETAILS: Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018-May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026.

Exposures: Intensive antiviral chemoprophylaxis with oseltamivir (>=70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents).

Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs).

Among 404 outbreaks in 318 NHs, 35,086 resident-trial observations (29,683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17,155 observations; 17,931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of -0.06% (95% CI, -0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of -0.96% (95% CI, -1.78% to -0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization. At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death.

Copyright © American Medical Association. All Rights Reserved.

Source: Silva, J. B. B., Hsieh, H. T., Howe, C. J., et al. Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks. JAMA Internal Medicine.. 2026; 186(6): 714-722. Published: June, 2026. DOI: 10.1001/jamainternmed.2026.0401

A Multisite Phase 3 Randomized Clinical Trial

[Posted 9/Jun/2026]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: In this parallel-group randomized clinical trial, mirtazapine delivered in routine clinical practice reduced methamphetamine use in adults with methamphetamine use disorder. No unexpected safety concerns delivering mirtazapine in this setting were found; this finding has important clinical implications in the absence of any approved pharmacotherapies for methamphetamine use disorder.

BACKGROUND: Methamphetamine use disorder is a global health challenge for which there are no approved pharmacotherapies. The safety and effectiveness of mirtazapine, a promising candidate for methamphetamine use disorder, has not been established in routine clinical practice. Purpose is to determine the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder in routine clinical practice.

DETAILS: This phase 3, parallel-group, double-blind, placebo-controlled randomized clinical trial was conducted between November 16, 2022, and May 1, 2025, at 6 outpatient alcohol and other drug clinics in Australia among adults with moderate to severe methamphetamine use disorder. Data analysis was conducted from May to September 2025. The primary end point was the change in days of methamphetamine use in the past 28 days from baseline to week 12. Secondary end points were depression, insomnia, HIV risk behavior, quality of life, and methamphetamine-negative oral fluid samples. Of 344 participants randomized, 339 participants received the intervention (167 in the placebo group and 172 in the mirtazapine group). Mean (SD) age was 42.0 (8.6) years, 126 participants (37.2%) were female, and participants had used methamphetamine for a median (IQR) of 24 days (17-28) of the past 28 days at baseline. The mean reduction in days of methamphetamine use from baseline to week 12 was greater in the mirtazapine group (7.0 days of 28 days) than in the placebo group (4.8 days of 28 days; mean difference, 2.2 days; 95% CI, -4.2 to -0.2 days; P = .02). More participants in the mirtazapine group reported drowsiness (47% vs 33%) and weight gain (10% vs 3%). Forty participants (23%) discontinued mirtazapine due to adverse events compared to 25 participants (15%) in the placebo group. No significant effects of mirtazapine on secondary end points were found.

Copyright © American Medical Association. All Rights Reserved.

Source: McKetin, R., Shoptaw, S., Saunders, L., et al. Mirtazapine for Methamphetamine Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2026; 83(6):581-589. Published: June, 2026. DOI: 10.1001/jamapsychiatry.2026.0159.