Anti-convulsants in the Treatment of Low Back Pain and Lumbar Radicular Pain: A Systematic Review and Meta-analysis

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SCIENCE
Anti-convulsants in the Treatment of Low Back Pain and Lumbar Radicular Pain: A Systematic Review and Meta-analysis
Key Take-Away: 

There is moderate-to high-quality evidence that anticonvulsants are ineffective for the treatment of low back pain or lumbar radicular pain. There is high-quality evidence that gabapentinoids have a higher risk of adverse events.

Globally, millions of people are suffered from low back pain (LBP) and become a major cause of disability than any other health complication. It is predicted that about 5% to 10% of patients with LBP have sciatica and followed by leg pain.

ABSTRACT: 
Background: 

Globally, millions of people are suffered from low back pain (LBP) and become a major cause of disability than any other health complication. It is predicted that about 5% to 10% of patients with LBP have sciatica and followed by leg pain. Few of the patients have also reported having neurogenic claudication, which is characterised by leg pain spinal stenosis and symptoms are worsened with physical activities (e.g., walking) and relieved by flexion (e.g., sitting).

Nonpharmacologic interventions and nonopioid analgesics are mostly recommended by the clinical guidelines for the treatment of LBP, rather than the potent painkillers such as anticonvulsants drugs.

The analgesic action of anticonvulsant medicines acts by limiting neuronal excitation and enhancing inhibition. Anticonvulsant drugs such as gabapentin and pregabalin, also known as gabapentinoids, have been reported to be beneficial in neuropathic pain conditions such as diabetic peripheral neuropathy. However, the none of the studies cleared the efficacy and safety of anticonvulsants in LBP and lumbar radicular pain. Therefore, the present systematic review aimed to evaluate the effectiveness and tolerability of anticonvulsants for the management of LBP and lumbar radicular pain.

Rationale behind research

  • None of the previous studies determined the safety and efficacy of gabapentinoids against LBP and lumbar radicular pain and also these studies were limited only to populations with chronic back pain
  • Therefore, Oliver Enke conducted this systematic review to evaluate the effectiveness and safety of anticonvulsant drugs for the management of LBP and lumbar radicular pain compared with placebo.

Objective

To determine the efficacy and tolerability of anticonvulsants in the treatment of low back pain and lumbar radicular pain compared with placebo. 

Methods: 

 

 

Study outcomes:

  • Primary outcomes: Pain and disability outcomes
  • Secondary outcomes: Safety outcomes
  • Risk of bias: Two reviewers (O.E., H.A.N.) individually evaluated the risk of bias using the 11-item Physiotherapy Evidence Database (PEDro) scale with disagreements resolved by consensus.
  • Assessment of heterogeneity: Heterogeneity was assessed by undertook pooling if heterogeneity was acceptable (e.g., I 2 < 75%) using a random-effects model.
  • Grading of evidence: The overall quality of evidence was assessed by using a Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which considered study design, the risk of bias, imprecision and inconsistency. For each domain the quality of evidence was downgraded by 1 or 2 levels, depending on whether a serious or a severe flaw was present. GRADE was applied in panel discussions, and the consensus was used to resolve any disagreement         
  • Time period: 2 weeks, 7 weeks, 6 months and 12 months
Results: 

 

Outcomes

  • Efficacy of anticonvulsants for low back pain with or without radiating leg pain: There was the high quality of evidence were found with no effect for pain in the short term (pooled MD –0.0, 95% CI –0.8 to 0.7 on a 0- to 10-point NPRS, 3 studies). Similarly, there was low quality of evidence for the treatment effect for pain in the intermediate term (MD –0.1, 95% CI –1.4 to 1.2 on a 0- to 10-point NPRS, 1 study). In case of disability, one study showed no treatment effect in the short term (MD –0.2, 95% CI –5.9 to 5.5 on a 100-point Oswestry Disability Index) with high-quality evidence.

One trial reported the topiramate as a small, clinically worthwhile treatment for pain in the short term (MD –11.4, 95% CI –16.7 to –6.1 on a 78-point pain scale), but in case of disability, showed no treatment effect in the short term (MD –4.9, 95% CI –19.4 to 9.6 on a 100-point Oswestry Disability Index).

  • Efficacy of anticonvulsants for lumbar radicular pain: Out of four studies, three studies provided data for inclusion in the forest plot. There was high-quality evidence of no effect on pain in the immediate (pooled MD –0.1, 95% CI –0.7 to 0.5 on a 0- to 10-point NPRS, 2 studies), intermediate (MD –0.1, 95% CI –0.9 to 0.7 on a 0- to 10-point NPRS, 1 study) and long-term (MD 0.4, 95% CI –0.5 to 1.3 on a 0- to 10-point NPRS, 1 study) respectively. There was also high-quality evidence of no effect for disability in the immediate (pooled SMD –0.1, 95% CI –0.3 to 0.2, 2 studies), short-term (MD 0.6, 95% CI –1.5 to 2.7) intermediate-term (MD –1.4, 95% CI –3.6 to 0.8) and long-term (MD 0.8, 95% CI –1.5 to 3.1).

There was the deficient quality of evidence of topiramate for pain (MD –0.7, 95% CI –2.1 to 0.6 on a 0- to 10-point NPRS)and disability (MD –2.0, 95% CI –10.0 to 6.0 on a 100-point Oswestry Disability Index).

  • Adverse events: Results of the current review collected the high-quality evidence that reported the high risk of adverse events with gabapentinoids as compared with placebo (pooled risk ratio [RR] 1.4, 95% CI 1.2 to 1.7, 6 studies). One study reported a total of 19 and 13 adverse events associated with gabapentin and placebo respectively used for chronic LBP. Drowsiness or sleepiness, dizziness and nausea were the most common adverse events reported in participants taking a gabapentinoid.

In the case of topiramate, out of 2 studies, one active placebo study showed the risk of adverse events (RR 1.2, 95% CI 0.9 to 1.6).

  • Other analyses: Only one study was included for the subgroup analysis, which included the patients with acute and chronic symptoms. When the impact of pregabalin was examined individually on the sciatica patients, there was no treatment effect for pain or disability.
Conclusion: 

This meta-analysis found moderate to the high-level quality of evidence reported the anticonvulsant as nonbeneficial for the treatment of LBP or lumbar radicular pain.

CMAJ. 2018 Jul 3;190(26):E786-93.
Therapeutic, Low back pain, Lumbar Radicular Pain, Back pain, Acute, Chronic, Pregabalin, Gabapentinoids, Anti-convulsants, Systematic Review, Meta-analysis, Efficacy, Safety,
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