Effect of Gabapentin vs Pregabalin on Pain Intensity in Adults With Chronic Sciatic

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Robertson K, Marshman LAG, Plummer D, Downs E. Effect of Gabapentin vs Pregabalin on Pain Intensity in Adults With Chronic Sciatica: A Randomized Clinical Trial. JAMA Neurol. 2019; 76: 28-34.

Clinical Question

In patients with chronic sciatica, is pregabalin more effective at reduction of pain and adverse effects than gabapentin?

Bottom Line

In patients with chronic sciatica, both gabapentin and pregabalin were beneficial, but gabapentin was more effective than pregabalin in reducing pain and had less severe adverse reactions with a NNH equaling 1. (19% vs. 81%)

Major Points

Chronic sciatica is defined as sciatic pain lasting longer than 3 months. It is often resistant to simple treatment regimens so anticonvulsant medications are added to those regimens. These medications most commonly include gabapentin and pregabalin. Overall, gabapentin and pregabalin decrease neurotransmitter release that is associated with neuropathic pain of chronic sciatica. The optimal treatment for chronic sciatica is unclear even though gabapentin and pregabalin are the go-to medications. This trial was used to determine whether gabapentin or pregabalin was the more efficient option for treating chronic sciatica.

In a randomized clinical trial, eighteen patients received either pregabalin for 8 weeks followed by gabapentin for 8 weeks with a one week wash out in between or gabapentin for 8 weeks followed by pregabalin with a one week wash out in between. It was seen that gabapentin was more successful at relieving chronic sciatica pain then pregabalin as well as having less adverse events.

Some criticisms for the study were the short amount of time on each drug. Some can say 8 weeks is an insufficient trial. The drugs also had to be titrated up to 300 mg twice daily for pregabalin and 800 three times daily for gabapentin. This can lead to an overestimate of adverse events due to the inability to titrate slowly. The trial only included 18 people.


Guidelines

No Guidelines

Design

  • Randomized Clinical Trial
  • Prospective, single-center, double-blind, randomized, double-dummy, crossover in patients with CS
  • Number of patients randomized = 18
  • Number of patients given gabapentin followed by pregabalin = 8
  • Number of patients given pregabalin followed by gabapentin = 10
  • Setting: Single center, tertiary referral public hospital
  • Enrollment: 18 weeks
  • Mean follow-up: none
  • Analysis: intention-to-treat
  • Primary outcome: leg pain intensity using the visual analog scale, patients rated their average leg pain out of 10 with 0 representing no pain and 10 representing worst pain imaginable

Population

  • Baseline Demographics: Patients with unilateral chronic sciatica
    • Total population: 18 (100%)
    • Age: 57 (16.5%)
    • Smokers: 5 (28%)
    • Alcohol intake: 12 (67%)
    • Men: 11 (61%)
    • Women: 7 (39%)
    • Adverse events: 12 (67%)
    • Efficacy: 18 (100%)
    • Concomitant medications:
      • Nonsteroidal anti-inflammatory drugs: 3 (17%)
      • Acetaminophen (+/- codeine): 10 (56%)
      • Opioid: 6 (33%)
      • Antiepileptic/anticonvulsant: 1 (5%)

Inclusion Criteria

  • Patients who have not used Gabapentin and pregabalin
  • Patients 18 years or older
  • Sufficient understanding of English


Exclusion Criteria

  • Pregnant, breastfeeding, women planning conception
  • History suggesting neuropathy due to genetics or other causes
  • Major organ system disease
  • Cardiovascular autonomic neuropathy
  • Baseline postural hypotension of more than 20 mm Hg
  • Contraindication to GBP or PGB (allergy or renal impairment)
  • Cancer, dementia, severe mental illness
  • Those unlikely to comply to procedures (high opiate tolerance)


Interventions

Randomly assigned participants received GBP (400 mg to 800 mg 3 times a day) then PGB (150 mg to 300 mg twice daily) or vice versa, each taken for 8 weeks. Crossover followed a 1-week washout


Outcomes

Primary Outcome

  • Primary: Leg Pain intensity at baseline and 8 weeks. (10-point visual analog scale)
    • Significant pain intensity VAS reduction was recorded at the end of an 8 week treatment period for GBP (mean (SD), 7.54 (1.39) to 5.82 (1.72); P < .001) and PGB (mean (SD), 7.33 (1.30) to 6.38 (1.88); P = .002)
    • GBP proved superior compared to PGB when compared for the reduction in Pain intensity VAS head to head.

Secondary Outcomes

  • Secondary: Disability and severity/ frequency of adverse events (Oswestry disability Index). The Scores ranged from 0 to 100, with higher scores indicating greater disability.
    • Significant ODI reduction was observed at 8 weeks for GBP (mean (SD), 59.22 (16.88) to 48.54 (15.52); P < .001) and PGB (mean (SD), 59.22 (13.24) to 50.44 (16.58); P < .001)

Adverse Events

  • Dizziness (13%), Drowsiness (13%), Nausea (11%). This were mostly associated with PGB compared to GBP. (81% vs 19%, P = .002, NNH=1.)

Criticisms

  • There is low recruitment for the study due to finding people with chronic sciatica who were not already prescribed gabapentin or pregabalin.
  • The participants were only on each medication for 8 weeks and this could be considered insufficient.
  • The study can overestimate adverse events due to the inability of slow titration.


Funding

This trial was funded by an internal grant received from the Townsville Hospital Study, Research and Education Trust Account. The funds were used to purchase consumables. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. There was no involvement with drug companies in reference to drug supply, trial conduct or manuscript review.

Further Reading

Robertson K, Marshman LAG, Plummer D, Downs E. Effect of Gabapentin vs Pregabalin on Pain Intensity in Adults With Chronic Sciatica: A Randomized Clinical Trial. JAMA Neurol. 2019; 76: 28-34.