Exploratory analysis of pregabalin clinical trials

Pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury: an exploratory analysis of pregabalin clinical trials | J Pain Res. 2016 | free full-text PMC article

Characterizing relationships between pain relief and function can inform patient management decisions. This analysis explored graphically the relationship between pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury in two clinical trials of pregabalin.

This was a post hoc analysis of two randomized, double-blind, clinical trials in patients who were treated with pregabalin (n=181) or placebo (n=172) for neuropathic pain associated with spinal cord injury.

Greater functional improvements were generally achieved at higher levels of clinically significant pain reduction. Pregabalin resulted in shifts from placebo toward greater functional improvement with greater pain relief.  

Why does it require high-level scientific research to determine that people are more functional if they have less pain. I can’t think of anyone this wouldn’t hold true for.

Introduction

Recent estimates suggest that as many as 273,000 individuals in the US have spinal cord injury (SCI), with ~12,000 new cases of SCI occurring annually.1

Among these individuals, ~40% also have chronic central neuropathic pain (NeP), a complication of SCI resulting from a lesion of the somatosensory pathways within the central nervous system.

The presence of pain in patients with SCI further

  • compromises function,
  • increases disability,
  • reduces quality of life, and
  • has been reported to be a contributory factor to unemployment and depression.

This sounds like an argument FOR opioids, since they are the most effective pain relievers for most people.

In particular, SCI-associated NeP has been shown to be associated with

  • a substantial socioeconomic burden, with
  • higher health care resource utilization and costs and
  • lower health status and productivity

observed at increasing levels of pain.

Again, these are good reasons to use whatever method is most effective in the patient to reduce their pain.

fewer days in rehabilitation and less rehabilitation treatment time were reported among patients with the highest pain severity levels relative to those with no pain and lower pain levels.

When pain is present, a core element of SCI management is pain reduction to a level that the patient considers acceptable, as complete relief is rarely possible.

A variety of pharmacologic interventions are available for SCI pain, and those especially used for NeP include

  • antidepressants,
  • antiepileptic drugs,
  • opioids, and
  • various intrathecal medications.

Currently, only pregabalin has received US Food and Drug Administration approval in the US for treatment of NeP associated with SCI.

With regard to function, moderate-to-strong correlations have been observed between pain intensity and interference with daily activities using various versions of the Brief Pain Inventory (BPI); higher levels of pain intensity consistently resulted in greater interference.

Unlike so much evidence for the restrictions of the CDC guidelines, there is good evidence of the harms resulting from chronic pain.

the goal of the current study was to explore the relationships between improvement in pain and changes in function among patients treated with pregabalin or placebo in the two clinical trials.

A broad definition of function was applied in order to encompass body functions, activity, and participation as described in the International Classification of Functioning, Disability, and Health.

I’ve left out the “Methods” and “Results” portions of the article which contain all the technical details.

Discussion

While similar trends in the association between pain reduction and function were observed both for pregabalin- and placebo-treated patients, suggesting robustness of the observations, the magnitude of the effects was consistently greater with pregabalin.

These results also support the concept that those who benefit in terms of pain relief also benefit in other areas.

However, the small incremental improvements in function are all that could be reasonably expected to be demonstrated, given the overall severe multiple SCI-related contributors to impairments in function

Overall, the most consistent relationship between pain and function appeared to be for sleep

Notably, only sleep outcomes appeared to show a linear progression across pain relief thresholds in the linear trend analysis.

For other functional outcomes, although statistical significance was shown in the linear trend analysis, this significance was primarily driven by the large change at ≥50% pain relief, with less distinction at the lower thresholds.

This matches my experience: there is a threshold of pain above which I cannot ignore it and can only lie down in misery and wait for my opioids to take effect (45-150min for me).

Below that threshold, pain no longer overwhelms my brain (thoughts and both physical and emotional feelings) and my focus changes back to “getting things done” and productive activity.

An important limitation of this analysis is that it was based on results from clinical trials, and thus may not be representative of clinical practice. Generalizability may also be limited since the population was predominantly male and comprised primarily of patients who were Whites or Asians

For patients with SCI-related NeP in two clinical trials of pregabalin, greater improvements in several functional domains associated with daily activities and quality of life were achieved at higher levels of pain reduction.

Only a scientist wouldn’t find this conclusion obvious. Perhaps doctors need to be reminded of this as well.

While the greatest improvements were experienced by patients who obtained the highest level of pain relief regardless of treatment allocation, pregabalin resulted in a shift to more pain relief and better function relative to placebo.

Since pain relief correlates with functionally, it makes even more sense to treat patients with whatever works best, even if that is opioids.

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