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, 12, 2577-2587
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The Relationship Between the Reporting of Euphoria Events and Early Treatment Responses to Pregabalin: An Exploratory Post-Hoc Analysis

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The Relationship Between the Reporting of Euphoria Events and Early Treatment Responses to Pregabalin: An Exploratory Post-Hoc Analysis

Bruce Parsons et al. J Pain Res.

Abstract

Background: Euphoria is a complex, multifactorial problem that is reported as an adverse event in clinical trials of analgesics including pregabalin. The relationship between the reporting of euphoria events and pregabalin early treatment responses was examined in this exploratory post-hoc analysis.

Methods: Data were from patients with neuropathic or non-neuropathic chronic pain enrolled in 40 randomized clinical trials, who received pregabalin (75-600 mg/day) or placebo. Reports of treatment-emergent euphoria events were based on the Medical Dictionary of Regulatory Activities preferred term "euphoric mood". Prevalence rates of euphoria events overall and by indication were assessed. Post-treatment endpoints included ≥30% improvements in pain and sleep scores up to 3 weeks as well as a ≥1-point improvement in daily pain score up to 11 days after treatment.

Results: 13,252 patients were analyzed; 8,501 (64.1%) and 4,751 (35.9%) received pregabalin and placebo, respectively. Overall, 1.7% (n=222) of patients reported euphoria events. Among pregabalin-treated patients, a larger proportion who reported euphoria events achieved an early pain response compared with those who did not report euphoria (30% pain responders in week 1 with euphoria events [43.0%], without euphoria events [24.2%]). Results were similar for weeks 2 and 3. For Days 2-11, a larger proportion of pregabalin-treated patients with (relative to without) euphoria events were 1-point pain responders. Findings were similar in pregabalin-treated patients for sleep endpoints (30% sleep responders in week 1 with euphoria events [50.7%], without euphoria events [36.1%]). Similar results were found for weeks 2 and 3. Patients who received placebo showed similar patterns, although the overall number of them who reported euphoria events was small (n=13).

Conclusion: In patients who received pregabalin for neuropathic or non-neuropathic chronic pain, those who experienced euphoria events may have better early treatment responses than those who did not report euphoria events.

Keywords: euphoria; pain; pregabalin; sleep.

Conflict of interest statement

RF reports consultancy and speaker fees in the past 2 years from AOP Orphan Pharmaceuticals, Eli Lilly, Grünenthal, Merck Selbstmedikation, Mitsubishi Tanabe Pharma, Pfizer Inc., and Scilex Pharmaceuticals, outside of the submitted work. SS is an employee of the University of Western Australia (UWA); within the last 2 years his employer has received honoraria, consulting fees and travel support from Andros Pharmaceuticals, Aspen, bioCSL, Eli Lilly, Grünenthal, Invidior, Janssen, Luye Pharma, Mundipharma, Pfizer Inc., Pierre Fabre, Seqirus, and iX Biopharma. BP, EW, MO, PBB, and LK are employees of Pfizer and have stock or stock options with Pfizer. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Proportion of 30% pain responders in pregabalin-treated patients who did and did not report euphoria events. Patients were classified as 30% pain responders if they had a ≥30% improvement in pain score (11-point NRS) from baseline. Number of patients who did and did not report euphoria events are shown for each week. Abbreviation: NRS, numeric rating scale.
Figure 2
Figure 2
Proportion of 1-point pain responders in pregabalin-treated patients who did and did not report euphoria events. Patients were classified as 1-point pain responders if they had a ≥1-point improvement in pain score (11-point NRS) from baseline. The number of patients who did and did not report euphoria events are shown for each day. Abbreviation: NRS, numeric rating scale.
Figure 3
Figure 3
Change in mean pain score from baseline for days euphoria events were reported. Data were determined only in those patients who reported euphoria events. Change in mean pain score was calculated as the difference between baseline pain score and daily pain score for each patient. If no end date of the euphoria event was reported, the last dosing date was used. Solid lines are the change in mean pain scores, dotted lines are the number of patients for each day for each treatment. The horizontal dotted line indicates zero change in mean pain score. Values below zero represent improvements in pain, those above zero represent worsening of pain.
Figure 4
Figure 4
Proportion of 30% sleep responders in pregabalin-treated patients who did and did not report euphoria events. Patients were classified as 30% sleep responders if they had a ≥30% improvement in sleep score from baseline. Data from studies that used PRSI or NRS sleep quality score are combined. Number of patients who did and did not report euphoria events are shown for each week. Abbreviations: NRS, numeric rating scale; PRSI, pain-related sleep interference.

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