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Combination treatment of neuropathic pain: Danish expert recommendations based on a Delphi process

Authors Holbech JV, Jung A, Jonsson T, Wanning M, Bredahl C, Bach FW

Received 27 March 2017

Accepted for publication 22 May 2017

Published 26 June 2017 Volume 2017:10 Pages 1467—1475

DOI https://doi.org/10.2147/JPR.S138099

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 3

Editor who approved publication: Dr Michael Schatman

Jakob Vormstrup Holbech,1 Anne Jung,2 Torsten Jonsson,3 Mette Wanning,4 Claus Bredahl,5 Flemming W Bach6

1Department of Neurology, Odense University Hospital, Odense, 2Medicinsk Fælles Ambulatorium, Holbaek Hospital, 3Aleris-Hamlet Hospitaler Ringsted, 4The Private Pain Clinic, Herlev, 5Clinic Acute Orthopedic Surgical Anesthesia Section, Aalborg Universitetshospital, Aalborg, 6Department of Neurology, Aarhus University Hospital, Aarhus, Denmark

Background:
Current Danish treatment algorithms for pharmacological treatment of neuropathic pain (NeP) are tricyclic antidepressants (TCA), gabapentin and pregabalin as first-line treatment for the most common NeP conditions. Many patients have insufficient pain relief on monotherapy, but combination therapy had not been included in guidelines until recently. Based on clinical empiricism and scientific evidence, a Delphi consensus process provided a consolidated guidance on pharmacological combination treatment of NeP.
Methods: A two-round virtual internet-based Delphi process with 6 Danish pain specialists was undertaken. In the first round, questions were answered individually and anonymously, whereas in the second round, the panel openly discussed first round’s summary of outcomes. Combinations of pharmacological pain treatments, that is, pregabalin/gabapentin, TCAs, serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors, opioids, other antiepileptics and cutaneous patches, were assessed based on both scientific and clinical practice experiences. The Centers for Disease Control and Prevention (CDC) grading system was used for evidence rating.
Results: Combination of pregabalin/gabapentin with TCA is useful in patients who do not gain sufficient pain relief or tolerate either drug in high doses, or to improve sleep disturbance. Also, combination of pregabalin/gabapentin and SNRIs is reasonably well documented and experienced by some experts to result in sufficient pain relief and fewer side effects than monotherapy. Good evidence on efficacy was found for the combination of pregabalin/gabapentin or TCAs and opioids, which was also frequently used in clinical practice. The evidence for combining TCAs and SNRIs is insufficient, although sometimes used in clinical practice despite the risk of serotonin syndrome. For localized NeP, combination therapy with cutaneous patches should be considered. There was insufficient scientific evidence for any pharmacologic combination therapies with selective serotonin reuptake inhibitors – as well as for other potential combinations.
Conclusions: The study revealed that combination therapy is widely used in clinical practice and supported by some scientific evidence. However, further studies are needed.

Keywords: neuropathic pain, combination therapy, Delphi panel, recommendations, CDC grading system, clinical practice

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