Benzodiazepines Tied to Worse Outcomes in Progressive Supranuclear Palsy

Of us with innovative supranuclear palsy (PSP) who were prescribed benzodiazepine derivatives had a sooner decline in PSP Rating Scale (PSPRS) rankings than of us who didn’t maintain benzodiazepines, a publish hoc diagnosis confirmed.

In a secondary diagnosis of concomitant remedy aged in a phase II/III scientific trial, most efficient one medication class — benzodiazepine derivatives, alongside side lorazepam, clonazepam, alprazolam, and diazepam — was related with more instant worsening of PSPRS rankings (P<0.001), reported Anne-Marie Wills, MD, MPH, of Massachusetts Accepted Effectively being facility in Boston, and co-authors.

Then all over again, benzodiazepine-related remedy equivalent to zolpidem, zopiclone, and eszopiclone were not related with worsening PSPRS rankings, they wrote in a JAMA Neurology learn letter.

“This explore is the main to search out out about on the consequences of medicines which can maybe well be aged clinically to treat PSP,” Wills suggested MedPage On the present time.

“We stumbled on that benzodiazepines are related with worthy sooner disease progression,” she said. “Here is main because these medicines are continuously prescribed to sufferers with PSP for insomnia and scare, among other indications.”

The findings counsel there can even very smartly be other modifiable elements that can have an effect on PSP progression, Wills added.

The researchers assessed 305 contributors within the phase II/III randomized trial of davunetide for PSP. For the reason that trial reported no treatment carry out, every the davunetide and placebo groups were integrated.

More than half of trial contributors were females (53%) and the suggest age at screening was about 68. Of 305 contributors, 44 (14.43%) took benzodiazepines and 38 (12.46%) took benzodiazepine-related remedy.

The explore spanned 52 weeks except November 2012. Its main consequence integrated repeated PSPRS measures, which assessed incapacity across six domains with a most accept of 100. Increased rankings indicated more disease worsening.

A major disagreement emerged between contributors not taking versus taking benzodiazepines at week 39 (7.52 vs 12.10 PSPRS points, P<0.001) and week 52 (10.02 vs 16.69 PSPRS points, P<0.001).

After adjusting for baseline disease severity and for benzodiazepine indications treasure insomnia, scare, sleep disturbance, confused out legs syndrome, and despair, contributors taking benzodiazepines experienced a median worsening of 17.1 PSPRS points per year, compared with 9.9 points per year for those not taking benzodiazepines.

“There was no disagreement between contributors prescribed benzodiazepines before versus within the course of the explore, arguing in opposition to sooner PSP progression main to benzodiazepine prescription,” Wills and co-authors noticed.

“Duration and dose of benzodiazepine publicity did not seem like related with the tempo of alternate in PSPRS, presumably because of the the exiguous sample dimension,” they added.

See limitations embody confounding by unmeasured variables and susceptibility to bias in a retrospective observational diagnosis, the researchers acknowledged. “We were unable to put any causal relationship between benzodiazepines and worsening disease,” they wrote. “In addition, infrequent explore visits precluded our ability to avoid losing in thoughts acute symptomatic effects of benzodiazepines.”

The davunetide trial enrolled most efficient of us with Richardson’s syndrome (primarily the most overall scientific presentation of PSP), and the findings of this secondary diagnosis should not generalizable to other PSP variants, they pointed out. The sample dimension of the benzodiazepine neighborhood and the pretty instant prepare-up within the trial are also limitations.

  • Judy George covers neurology and neuroscience files for MedPage On the present time, writing about mind rising old, Alzheimer’s, dementia, MS, rare ailments, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, worry, and more. Apply


This explore was supported by the Geraldine Dolce Fund for Progressive Supranuclear Palsy at Massachusetts Accepted Effectively being facility and a grant from the Nationwide Institute on Increasing old (NIA).

Wills reported receiving NIA grants and serving on the steerage committee for Amylyx Pharmaceuticals. Co-authors reported relationships with AbbVie, AFFiRis, Alector, Amylyx, APRINOIA, Biogen, BioAdvance, Biohaven, BioVie, BlueRock, Bristol Myers Squibb, Cavion, CoA Therapeutics, Denali, Janssen, Jazz, Eli Lilly, Novartis, Paladin, Pharma Two B, PsychoGenetics, Roche, Solar Pharma, UCB, Allon, AI Therapeutics, Ferrer, IQVIA, Mitochon, Switch, CurePSP, NIH, Rainwater Charitable Foundation, Regeneron, Arvinas, Alzprotect, Modalis, Merck, Oligomerix, Oscotec, and Transposon. Some co-authors also reported patents or book royalties.

Critical Provide

JAMA Neurology

Provide Reference: Iyer JM, et al “Concomitant medicines for innovative supranuclear palsy: a secondary diagnosis of a randomized scientific trial” JAMA Neurol 2024; DOI: 10.1001/jamaneurol.2023.5215.

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