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People with progressive supranuclear palsy (PSP) who were prescribed benzodiazepine derivatives had a faster decline in PSP Rating Scale (PSPRS) scores than those who didn't have benzodiazepines, a post hoc analysis showed.

In a secondary analysis of concomitant drugs used in a phase II/III clinical trial, only one medication class -- benzodiazepine derivatives, including lorazepam, clonazepam, alprazolam, and diazepam -- was associated with more rapid worsening of PSPRS scores (P<0.001), reported Anne-Marie Wills, MD, MPH, of Massachusetts General Hospital in Boston, and co-authors.

However, benzodiazepine-related drugs such as zolpidem, zopiclone, and eszopiclone were not associated with worsening PSPRS scores, they wrote in a research letter.

"This study is the first to look at the effects of medications that are used clinically to treat PSP," Wills told MedPage Today.

"We found that benzodiazepines are associated with much faster disease progression," she said. "This is important because these medications are commonly prescribed to patients with PSP for insomnia and anxiety, among other indications."

The findings suggest there may be other modifiable factors that can affect PSP progression, Wills added.

The researchers assessed 305 participants in the phase II/III randomized for PSP. Because the trial reported , both the davunetide and placebo groups were included.

More than half of trial participants were women (53%) and the mean age at screening was about 68. Of 305 participants, 44 (14.43%) took benzodiazepines and 38 (12.46%) took benzodiazepine-related drugs.

The study spanned 52 weeks until November 2012. Its main outcome included repeated measures, which assessed disability across six domains with a maximum score of 100. Higher scores indicated more disease worsening.

A significant difference emerged between participants 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 like insomnia, anxiety, sleep disturbance, restless legs syndrome, and depression, participants taking benzodiazepines experienced a mean worsening of 17.1 PSPRS points per year, compared with 9.9 points per year for those not taking benzodiazepines.

"There was no difference between participants prescribed benzodiazepines before versus during the study, arguing against faster PSP progression leading to benzodiazepine prescription," Wills and co-authors observed.

"Duration and dose of benzodiazepine exposure did not appear to be associated with the rate of change in PSPRS, perhaps due to the limited sample size," they added.

Study limitations include confounding by unmeasured variables and susceptibility to bias in a retrospective observational analysis, the researchers acknowledged. "We were unable to establish any causal relationship between benzodiazepines and worsening disease," they wrote. "In addition, infrequent study visits precluded our ability to evaluate acute symptomatic effects of benzodiazepines."

The davunetide trial enrolled only people with Richardson's syndrome (the most common clinical presentation of PSP), and the findings of this secondary analysis are not generalizable to other PSP variants, they pointed out. The sample size of the benzodiazepine group and the relatively short follow-up in the trial also are limitations.

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