An evidence-based review of pregabalin for the treatment of fibromyalgia

<p><b>Objectives:</b> Pregabalin, an α2-δ agonist, is approved for the treatment of fibromyalgia (FM) in the United States, Japan, and 37 other countries. The purpose of this article was to provide an in-depth, evidence-based summary of pregabalin for FM as demonstrated in randomized, placebo-controlled clinical studies, including open-label extensions, meta-analyses, combination studies and post-hoc analyses of clinical study data.</p> <p><b>Methods:</b> PubMed was searched using the term “pregabalin AND fibromyalgia” and the Cochrane Library with the term “pregabalin”. Both searches were conducted on 2 March 2017 with no other date limits set.</p> <p><b>Results:</b> Eleven randomized, double-blind, placebo-controlled clinical studies were identified including parallel group, two-way crossover and randomized withdrawal designs. One was a neuroimaging study. Five open-label extensions were also identified. Evidence of efficacy was demonstrated across the studies identified with significant and clinically relevant improvements in pain, sleep quality and patient status. The safety and tolerability profile of pregabalin is consistent across all the studies identified, including in adolescents, with dizziness and somnolence the most common adverse events reported. These efficacy and safety data are supported by meta-analyses (13 studies). Pregabalin in combination with other pharmacotherapies (7 studies) is also efficacious. Post-hoc analyses have demonstrated the onset of pregabalin efficacy as early as 1–2 days after starting treatment, examined the effect of pregabalin on other aspects of sleep beyond quality, and shown it is effective irrespective of the presence of a wide variety of patient demographic and clinical characteristics.</p> <p><b>Conclusions:</b> Pregabalin is a treatment option for FM; its clinical utility has been comprehensively demonstrated.</p

Anatomical localization of significant differences in DTI and TDI measurements between UCPPS patients (<i>N = 45</i>) and HCs (<i>N = 56</i>).

<p>A) Observed differences in mean diffusivity (MD). B) Observed differences in fractional anisotropy (FA). C) Observed differences in fiber track density. D) Observed differences in generalized anisotropy (GA). Significant clusters were determined by thresholding based on level of statistical significance (<i>P < 0</i>.<i>05</i>) and cluster-based corrections using random permutation analysis. Left column illustrates differences projected onto representative white matter fiber tracts.</p

Anatomical regions and corresponding cluster volumes showing significant differences in fiber track density on TDI between UCPPS patients and HCs (HCs).

<p>Minimum cluster size = 111 uL from permutation analysis.</p

Correlation matrix between mean MD measurements and MAPP symptom scores in UCPPS patients, localized to ROIs identified as different between UCPPS and HCs on statistical parameter maps.

<p>Dendrograms on the left side of the correlation matrix show hierarchical clustering of ROIs based on the association between MD measurements and symptom scores. Images showing ROI localization are chosen for select associations. Up arrows within cells denote significantly positive correlations (<i>P<0</i>.<i>05</i>) and down arrows within cells denote significantly negative correlations (<i>P<0</i>.<i>05</i>). (Note the level of significance was not corrected for multiple comparisons in this exploratory analysis).</p

Correlation matrix between mean track density measurements and MAPP symptom scores in UCPPS patients, localized to ROIs identified as different between UCPPS and HCs on statistical parameter maps.

<p>Dendrograms on the left side of the correlation matrix show hierarchical clustering of ROIs based on the association between track density measurements and symptom scores. Images showing ROI localization are chosen for select associations. Up arrows within cells denote significantly positive correlations (<i>P<0</i>.<i>05</i>) and down arrows within cells denote significantly negative correlations (<i>P<0</i>.<i>05</i>). (Note the level of significance was not corrected for multiple comparisons in this exploratory analysis).</p

Sex differences in fiber track density within A) UCPPS patients, B) positive control patients with IBS, and C) healthy control (HC) participants.

<p>Significant clusters were determined by thresholding based on level of statistical significance (<i>P < 0</i>.<i>05</i>) and cluster-based corrections using random permutation analysis.</p

Anatomical regions and corresponding cluster volumes showing significant differences in MD between UCPPS patients and HCs (HCs).

<p>Minimum cluster size = 171 uL from permutation analysis.</p

Anatomical localization of significant differences in DTI and TDI measurements between UCPPS patients (<i>N = 45</i>) and positive control patients with IBS (<i>N = 39</i>).

<p>A) Observed differences in mean diffusivity (MD). B) Observed differences in fractional anisotropy (FA). C) Observed differences in fiber track density. D) Observed differences in generalized anisotropy (GA). Significant clusters were determined by thresholding based on level of statistical significance (<i>P < 0</i>.<i>05</i>) and cluster-based corrections using random permutation analysis. Left column illustrates differences projected onto representative white matter fiber tracts.</p

Sex differences in mean diffusivity (MD) within A) UCPPS patients, B) positive control patients with IBS, and C) healthy control (HC) participants.

<p>Significant clusters were determined by thresholding based on level of statistical significance (<i>P < 0</i>.<i>05</i>) and cluster-based corrections using random permutation analysis.</p

Anatomical regions and corresponding cluster volumes showing significant differences in FA between UCPPS patients and HCs (HCs).

<p>Minimum cluster size = 111 uL from permutation analysis.</p