Effectiveness and Safety of Tapentadol Prolonged Release (PR) Versus a Combination of Tapentadol PR and Pregabalin for the Management of Severe, Chronic Low Back Pain With a Neuropathic Component: A Randomized, Double-blind, Phase 3b Study

Pain Pract. 2015 Jun;15(5):455-70. doi: 10.1111/papr.12200. Epub 2014 Apr 17.


Objective: To evaluate the effectiveness and tolerability of tapentadol PR monotherapy versus tapentadol PR/pregabalin combination therapy for severe, chronic low back pain with a neuropathic component.

Methods: Eligible patients had painDETECT "unclear" or "positive" ratings and average pain intensity ≥ 6 (11-point NRS-3 [average 3-day pain intensity]) at baseline. Patients were titrated to tapentadol PR 300 mg/day over 3 weeks. Patients with ≥ 1-point decrease in pain intensity and average pain intensity ≥ 4 were randomized to tapentadol PR (500 mg/day) or tapentadol PR (300 mg/day)/pregabalin (300 mg/day) during an 8-week comparative period.

Results: In the per-protocol population (n = 288), the effectiveness of tapentadol PR was clinically and statistically comparable to tapentadol PR/pregabalin based on the change in pain intensity from randomization to final evaluation (LOCF; LSMD [95% CI], -0.066 [-0.57, 0.43]; P < 0.0001 for noninferiority). Neuropathic pain and quality-of-life measures improved significantly in both groups. Tolerability was good in both groups, in line with prior trials in the high dose range of 500 mg/day for tapentadol PR monotherapy, and favorable compared with historical combination trials of strong opioids and anticonvulsants for combination therapy. The incidence of the composite of dizziness and/or somnolence was significantly lower with tapentadol PR (16.9%) than tapentadol PR/pregabalin (27.0%; P = 0.0302).

Conclusions: Tapentadol PR 500 mg is associated with comparable improvements in pain intensity and quality-of-life measures to tapentadol PR 300 mg/pregabalin 300 mg, with improved central nervous system tolerability, suggesting that tapentadol PR monotherapy may offer a favorable treatment option for severe low back pain with a neuropathic component.

Keywords: chronic pain; combination therapy; low back pain; neuropathic pain; randomized controlled trial; tapentadol prolonged release.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analgesics / administration & dosage
  • Chronic Pain / diagnosis
  • Chronic Pain / drug therapy
  • Delayed-Action Preparations / administration & dosage
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Internationality
  • Low Back Pain / diagnosis
  • Low Back Pain / drug therapy*
  • Male
  • Middle Aged
  • Neuralgia / diagnosis
  • Neuralgia / drug therapy*
  • Pain Management / methods*
  • Phenols / administration & dosage*
  • Pregabalin / administration & dosage*
  • Severity of Illness Index*
  • Tapentadol
  • Treatment Outcome


  • Analgesics
  • Delayed-Action Preparations
  • Phenols
  • Pregabalin
  • Tapentadol