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Donepezil provides positive effects to patients treated with gabapentin for neuropathic pain: an exploratory study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
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2014 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 1, 61-73 p.Article in journal (Refereed) Published
Abstract [en]

BackgroundThe first-line medication gabapentin and the acetylcholinesterase inhibitor donepezil represent a new promising combination to improve treatment outcomes for patients with severe neuropathic pain. The drugs have previously shown synergism following co-administration in nerve-injured rats. MethodsThe clinical relevance of adding donepezil to existing gabapentin treatment in patients with post-traumatic neuropathic pain was explored in this open-label study. The study comprised two consecutive periods of minimum 6 weeks: (1) titration of gabapentin to the highest tolerable dose or maximum 2400mg daily, and (2) addition of donepezil 5mg once daily to the fixed gabapentin dose. Efficacy and tolerability were assessed by ratings of pain intensity, questionnaires for pain and health-related quality of life, and reporting of adverse events. Pain scores were also analysed using mixed-effects analysis with the software NONMEM to account for intersubject variability. ResultsEight patients commenced treatment with donepezil, of which two withdrew because of adverse events. Addition of donepezil resulted in clinically relevant reductions of pain (>11 units on a 0-100 scale) and improved mental wellness in three of six patients. The remaining three patients had no obvious supplemental effect. Mixed-effects analysis revealed that pain scores were significantly lower during co-administration (P<0.0001 combination vs. monotherapy). ConclusionDonepezil may provide additional analgesia to neuropathic pain patients with insufficient pain relief from gabapentin as monotherapy. The promising results support controlled clinical trials of the drug combination. The usefulness of mixed-effects analysis in small-scale trials and/or for data with high intersubject variability was also demonstrated.

Place, publisher, year, edition, pages
2014. Vol. 58, no 1, 61-73 p.
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Medical and Health Sciences
URN: urn:nbn:se:uu:diva-215267DOI: 10.1111/aas.12218ISI: 000328156800009OAI: oai:DiVA.org:uu-215267DiVA: diva2:687139
Available from: 2014-01-13 Created: 2014-01-13 Last updated: 2014-01-13Bibliographically approved

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Butler, StephenGordh, Torsten E.
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Family Medicine and Preventive MedicineDepartment of Public Health and Caring SciencesAnaesthesiology and Intensive Care
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