OBJECTIVE: Pooled analysis of nabiximols and placebo in randomized controlled studies (RCTs) of chronic neuropathic pain.
DESIGN: Systematic review and meta-analysis.
METHODS: A systematic literature search was conducted to identify double-blind placebo-controlled RCTs of nabiximols for chronic neuropathic pain. The clinical endpoint of interest was change from baseline in mean pain score on 11-point numerical rating scales. Mean difference (MD) and standardized mean difference (SMD, Hedges' g) were calculated using fixed effect (FE) and random effects (RE) models. Strength of evidence was assessed using the Cochrane Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Risk of bias was assessed using the revised Cochrane risk-of-bias tool (RoB 2).
RESULTS: Nine RCTs with 1289 participants were included. Quality of evidence (GRADE) was moderate. One study had a high risk of bias (RoB 2) and five had some concerns. For the pooled endpoint of change from baseline in mean pain score, nabiximols was superior to placebo, with a MD of -0.40 (95% confidence interval [CI]: -.59 to -.21; FE, P < .0001) or -0.44 (95% CI: -.70 to -.19; RE, P = .0006). A SMD of -0.21 (95% CI: -.32 to -.10; FE) or -0.26 (95% CI: -.42 to -.10; RE) indicated an incremental benefit over background analgesia. Results in favor of nabiximols were maintained in sensitivity analyses.
CONCLUSIONS: Nabiximols was superior to placebo for reduction of chronic neuropathic pain, with a small effect size. Larger RCTs designed to assess the effect of nabiximols in neuropathic pain are required to reach more definitive conclusions.
Modest benefits; industry-funded studies? Sativex is not covered by the Provincial drug plan in Ontario.
This is a systematic review and meta-analysis of double-blind placebo-controlled RCTs of nabiximols for chronic neuropathic pain. Nine RCTs with 1289 participants were included. Results-Nabiximol was superior to placebo for reduction of chronic neuropathic pain. It may be newsworthy for endocrinologists, as it provides a possible new medication for management of painful diabetic neuropathy.
Relevant information with the increasing use of cannabinoids, but reported in a way that makes it difficult to adapt the results clinically. There is small effect size and poor quality data overall.
This meta-analysis was well performed but the conclusion remains that, despite possibly having an add-on effect on pain relief, larger RCTs are needed to ascertain this for specific populations. As an oncologist, I find that this review was not particularly helpful because it mainly focused on others etiologies for chronic neuropathic pain. A point of note is that, despite sound methodology, the main author seems to be an employee of a company with commercial interests in the product.