Amitriptyline-perphenazine therapy for persistent idiopathic facial pain: translational perspectives from a retrospective study.

Background: Persistent idiopathic facial pain (PIFP) can be challenging, both in its diagnosis, which appears to be purely exclusionary, and in its treatment, which currently lacks a gold standard. Amitriptyline is considered a first-line therapy, although not always effective. Recent insights into the role of dopamine in facial pain suggest that a novel therapeutic approach could target the dopamine system.

Methods: This study aimed to retrospectively evaluate the efficacy of treatment with amitriptyline-perphenazine association in patients with severe PIFP. Thirty-one patients were given a regimen dose of amitriptyline-perphenazine at dosages ranging between 10/2 and 20/4 mg and were then retrospectively analyzed. We evaluated the following outcomes, referred to the last week prior to follow-up visits: NRS score for pain intensity (minimum, maximum, and average), the number of attacks, and SF-36 questionnaire for quality of life. Comparisons were made between pre- and post-treatment.

Results: Thirty-one patients over 35 were screened. At baseline, average NRS was 5 ± 0.93 (CI 95%: 4.6-5.3), and the median number of breakthrough episodes over last week was 5 ± 1.57 (CI 95%: 4-6) with a maximum NRS = 9 ± 0.89 (CI 95%: 8-9). After treatment, average NRS was 4.1 ± 0.93 (CI 95%: 3.8-4.5; p < 0.001), maximum NRS was 6.1 ± 1.60 (CI 95%: 5.5-6.6), and the median number of attacks was 4 ± 0.99 (IC 95%: 3-4) (p < 0.001). Regarding SF-36 questionnaire, the most improved parameters were quality of life related to pain (25.89 ± 12.48 vs 31.19 ± 13.44; p < 0.001) and physical function (69.56 ± 17.84 vs 84.17 ± 20.99; p < 0.001).

Conclusion: Despite limitations, the pain scores, the frequency of the attacks, and quality of life were found to be significantly improved after treatment. Although results are not broad based given the small sample size, the combination of amitriptyline and perphenazine may be an effective and well-tolerated treatment in patients with PIFP. It is abundantly clear that dopaminergic pathways play a key role in pain modulation, yet the underlying mechanisms have not been fully understood, requiring further investigation.