Dextroamphetamine Fails to Improve Post-Stroke Motor Recovery

Larry B. Goldstein, MD, the chair of the Department of Neurology and co-director of the Kentucky Neuroscience Institute

Larry B. Goldstein, MD

Dextroamphetamine in combination with physiotherapy failed to improve motor recovery in patients who had strokes.

Despite animal models revealing task-relevant training combined with dextroamphetamine facilitated recovery after a focal brain injury, clinical trials in patients post-stroke have been inconclusive. This trial, led by Larry B. Goldstein, MD, the chair of the Department of Neurology and co-director of the Kentucky Neuroscience Institute, found that there were no significant differences in the change in Fugl-Meyer motor scores from baseline to 3 months.¹

“One or 2 [clinical trials] have shown positive effects, whereas the others didn’t,” Goldstein said in an interview with JAMA Neurology.² “There are a variety of potential reasons for that related to drug dose, timing, combination with physical therapy, among others, that may have explained that. This study was really aimed at trying to better understand some of those factors.”

The pilot, double-blind, block-randomized trial included 64 patients with cortical or subcortical ischemic stroke and moderate to severe motor deficits to either 10 mg dextroamphetamine (n = 32) or placebo (n = 32) in combination with 1-hour physical therapy sessions to begin 1 hour post-administration every 4 days for 6 sessions, in addition to standard rehabilitation. The mean (SE) change in Fugl-Meyer motor scores at 3 months was —18.65 (2.27) with dextroamphetamine compared to –20.83 (2.94) with placebo (P = .58).

Among subgroups, the results were similar. For those with cortical ischemic stroke and severe symptoms, the mean changes were —19.63 (3.64) with dextroamphetamine and –13.50 (5.07) with placebo (P = .35). For those with subcortical stroke and severe symptoms, the mean change was —14.55 (2.28) with the drug and –21.18 (4.55) with placebo (P = .39). For those with moderate symptoms and cortical or subcortical stroke, the respective rates of change for dextroamphetamine were —14.17 (1.96) and –29.3 (8.88), compared to the respective changes with placebo of –34.75 (7.60; P = .054) and —14.80 (3.92; P = .36).

“Of course, we were disappointed,” Goldstein said. “The whole purpose of this study was really to lead to the development of a new therapeutic approach for patients who have had motor deficits after stroke. This is based on extensive animal data over many, many decades now, as well as some preliminary clinical data, so the hope was that we’d have an overall effect, or at least an overall effect in the subgroup of patients we thought was most likely to benefit, but we didn’t find that.”

In terms of adverse events (AEs), there were 5 patients that did not complete the protocol in the placebo group, none of which were due to a protocol-specified cause. No treatment-associated serious AEs occurred.

Goldstein and colleagues noted that possibly, a different amphetamine dose, different administration schedule, or a modified patient population could possibly show a benefit, though further research would need to evaluate this. Additionally, they acknowledged that since the study was conducted, acute thrombectomy was shown to be an effective treatment and physiotherapeutic methods may have evolved—both which could influence the effect of drugs such as dextroamphetamine during functional recovery after stroke.

“I think there’s a lot that we can continue to explore, and again, this was an exploratory pilot trial, although we powered it for a clinically significant effect,” Goldstein said. “Given the diverse patient population even though it was fairly highly selective, it’s not totally surprising that we didn’t see that effect. But even in the animal models, there are a number of very important variables that need to be better understood.”

REFERENCES:

1. Goldstein LB, Lennihan L, Radbadi M, et al. Effect of dextroamphetamine on poststroke motor recovery: a randomized clinical trial. JAMA Neurol. Epub August 27, 2018. doi: 10.1001/jamaneurol.2018.2338

2. JAMA Neurology. Effect of Dextroamphetamine on Poststroke Motor Recovery. JAMA Network. jamanetwork.com/learning/audio-player/16722472. Published August 27, 2018. Accessed August 28, 2018.