Shanthanna H, Gilron I, Rajarathinam M, AlAmri R, Kamath S,
Thabane L, Devereaux PJ, Bhandari M. Benefits and safety of
gabapentinoids in chronic low back pain: A systematic review and meta-analysis of
randomized controlled trials. PLoS Med. 2017 Aug 15;14(8):e1002369.
Abstract
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.
METHODS:
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.
RESULTS:
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.
Courtesy of a colleague
No comments:
Post a Comment