PLoS Medicine · August 15, 2017
Authors: Harsha Shanthana et al
Background And Objective
Chronic Low Back Pain (CLBP) is very common, with a lifetime prevalence between 51% and 80%. In majority, it is nonspecific in nature and multifactorial in etiology. Pregabalin (PG) and Gabapentin (GB) are gabapentinoids that have demonstrated benefit in neuropathic pain conditions. Despite no clear rationale, they are increasingly used for nonspecific CLBP. They necessitate prolonged use and are associated with adverse effects and increased cost. Recent guidelines from the National Health Service (NHS), England, expressed concerns on their off-label use, in addition to the risk of misuse. We aimed to assess the effectiveness and safety of gabapentinoids in adult CLBP patients.
Electronic databases of MEDLINE, EMBASE, and Cochrane were searched from their inception until December 20th, 2016. We included randomized control trials reporting the use of gabapentinoids for the treatment of CLBP of >3 months duration, in adult patients. Study selection and data extraction was performed independently by paired reviewers. Outcomes were guided by Initiative on Methods, Measurement and Pain Assessment in Clinical Trials guidelines, with pain relief and safety as the primary outcomes. Meta-analyses were performed for outcomes reported in 3 or more studies. Outcomes were reported as mean differences (MDs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs), and I2 in percentage representing the percentage variability in effect estimates that could be explained by heterogeneity. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of evidence.
Out of 1,385 citations, eight studies were included. Based on the interventions and comparators, studies were analyzed in 3 different groups. GB compared with placebo (3 studies, n = 185) showed minimal improvement of pain (MD = 0.22 units, 95% CI [−0.5 to 0.07] I2 = 0%; GRADE: very low). Three studies compared PG with other types of analgesic medication (n = 332) and showed greater improvement in the other analgesic group (MD = 0.42 units, 95% CI [0.20 to 0.64] I2 = 0; GRADE: very low). Studies using PG as an adjuvant (n = 423) were not pooled due to heterogeneity, but the largest of them showed no benefit of adding PG to tapentadol. There were no deaths or hospitalizations reported. Compared with placebo, the following adverse events were more commonly reported with GB: dizziness-(RR = 1.99, 95% CI [1.17 to 3.37], I2 = 49); fatigue (RR = 1.85, 95% CI [1.12 to 3.05], I2 = 0); difficulties with mentation (RR = 3.34, 95% CI [1.54 to 7.25], I2 = 0); and visual disturbances (RR = 5.72, 95% CI [1.94 to 16.91], I2 = 0). The number needed to harm with 95% CI for dizziness, fatigue, difficulties with mentation, and visual disturbances were 7 (4 to 30), 8 (4 to 44), 6 (4 to 15), and 6 (4 to 13) respectively. The GRADE evidence quality was noted to be very low for dizziness and fatigue, low for difficulties with mentation, and moderate for visual disturbances. Functional and emotional improvements were reported by few studies and showed no significant improvements.
Conclusions And Relevance
Existing evidence on the use of gabapentinoids in CLBP is limited and demonstrates significant risk of adverse effects without any demonstrated benefit. Given the lack of efficacy, risks, and costs associated, the use of gabapentinoids for CLBP merits caution. There is need for large high-quality trials to more definitively inform this issue.
Why Was This Study Done?
Chronic low back pain (CLBP) is widely prevalent, and in majority it is nonspecific (no clear etiology) in nature. Among chronic conditions, CLBP is noted to be the leading cause of years lived with disability.
Gabapentin (GB) and Pregabalin (PG) have been shown to be helpful in neuropathic pain conditions, such as diabetic neuropathy. Despite no clear rationale, their use for CLBP has significantly increased.
We examined the existing literature and strength of evidence to determine the usefulness of either PG or GB in decreasing pain and improving functions, and the potential adverse effects of PG and GB, in patients with predominant CLBP.
What Did The Researchers Do And Find?
We performed a systematic review and meta-analysis of randomized control studies that used either PG or GB in patients of predominant CLBP.
We identified only 8 randomized control studies that assessed the benefits of using GB or PG in CLBP.
While GB showed minimal improvement of pain compared to placebo, pain relief with PG was inferior compared to the active analgesic group. GB and PG were both associated with increased risk of dizziness compared with placebo or active comparator, respectively. GB was additionally associated with increased risk of fatigue, visual disturbances, and difficulties with mentation compared with placebo.
What Do These Findings Mean?
There is limited evidence to support the use of either PG or GB in nonspecific CLBP.
The limited and low-quality evidence suggests increased risk of adverse effects with only minimal benefit for GB compared with placebo and no evidence for benefit with PG compared with other analgesics.
Their continued use in CLBP merits caution.