Background & Aims

Neuropathic pain (NP) is ‘pain that arises as a direct consequence of a lesion or disease affecting the somatosensory system’ and is associated with unpleasant sensations that include burning, pins and needles, electric-shocks, and numbness [1, 2]. NP affects 7%-10% of the general population and has a substantial negative effect on people’s quality of life even compared to those experiencing other types of chronic pain [3, 4]. NP pharmacotherapy recommendations include gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, tramadol, lidocaine, and capsaicin [5]. Despite the existing treatment guidelines and variety of choice, several studies indicate that a large proportion of people with NP do not use the recommended medications [6, 7]. The reasons for this are unclear. Therefore, we carried out a systematic review to elucidate predictors of NP pharmacotherapy prescribing, adherence, and discontinuation.

Methods

Our protocol was registered to PROSPERO (CRD42023464307). To identify relevant studies, electronic database searches were conducted in Embase, PubMed, Web of Science, and CINAHL Plus. Studies were included if they: investigated predictors of NP pharmacotherapy prescribing, adherence, or discontinuation in adults with NP; were a cohort study, case-control study, cross-sectional study, randomised controlled trial, or review with a meta-analysis, and; were available in full-text in English. Two reviewers independently carried out the study selection, data extraction, and risk of bias assessment. Discrepancies were resolved by discussion. The extracted information included: the first author, date of publication, study design, country, source of participants, time period of when the data was collected, sample size, sample age, sample gender, medications that were investigated, NP diagnoses included in the study, type of outcome, predictors investigated, and summary of main findings.

Results

Of 6,423 identified records, 48 were included. Predictors for prescribing, adherence and discontinuation were assessed in 33, 12 and 19 studies, respectively. The studies were heterogeneous in terms of which medications were included in the analysis, which predictors were analysed, and how the outcomes were measured. Having diabetic neuropathy and white ethnicity increased the likelihood of receiving recommended NP pharmacotherapy. Better adherence was observed in those with brand-name medication, dose titration, and at least a minimally effective dose. Shorter duration to discontinuation was associated with having moderate or severe adverse events, combination pharmacotherapy, subtherapeutic dose, lacking dose titration, longer duration of pain, pain-related worrying, and not experiencing pain relief. The results also showed that most people discontinued their treatment by 3-5 months even if they belonged to a group with predictors that were associated with longer therapy duration.

Conclusions

Many of the predictors (e.g. age, sex, comorbidities) discussed in the included studies had conflicting results between studies, study cohorts, or type of assessment. The predictors that had consistent results tended to have small effect sizes. Results with large effect sizes were generally accompanied with large confidence intervals. Overall, the studies indicate that people adhere well to NP pharmacotherapy but discontinue the treatment after a few months – regardless of the presence of any predictors. The proportion of people with NP receiving recommended treatment varied greatly between the studies (30% to 75%), but again the variation by predictors was fairly small. These results suggest discontinuation may be a bigger reason for the lack of NP medication use rather than their prescribing. The current literature lacks predictors for identifying people who persist with NP pharmacotherapy for long term.

References

[1] Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson PM, Hughes R, Nurmikko TM, Serra J. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008 Apr 29;70(18):1630-5.

[2]Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114:29–36. https://doi.org/10.1016/j.pain.2004.12.010.

[3] van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: A systematic review of epidemiological studies. Pain 2014;155:654–62. https://doi.org/10.1016/j.pain.2013.11.013.

[4] Langley PC, Van Litsenburg C, Cappelleri JC, Carroll D. The burden associated with neuropathic pain in Western Europe. J Med Econ 2013;16:85–95. https://doi.org/10.3111/13696998.2012.729548.

[5]Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015;14:162–73. https://doi.org/10.1016/S1474-4422(14)70251-0.

[6] Callaghan B, Reynolds E, Banerjee M, Kerber K, Skolarus L, Burke J. Longitudinal pattern of pain medication utilization in peripheral neuropathy patients. Pain. 2019 Mar;160(3):592. https://doi.org/10.1097/j.pain.0000000000001439.

[7] Gustavsson A, Bjorkman J, Ljungcrantz C, Rhodin A, Rivano-Fischer M, Sjolund KF, Mannheimer C. Pharmacological treatment patterns in neuropathic pain—lessons from Swedish administrative registries. Pain Medicine. 2013 Jul 1;14(7):1072-80. https://doi.org/10.1111/pme.12095.

Presenting Author

Mia Koponen

Poster Authors

Mia Koponen

BSc (Hons), MSc

University of Dundee

Lead Author

Dhaneesha Senaratne

University of Dundee

Lead Author

Harry Hebert

University of Dundee

Lead Author

Blair H. Smith

University of Dundee

Lead Author

Lesley Colvin

University of Dundee

Lead Author

Topics

  • Systematic Reviews/Meta-Analysis