Introduction
The prevalence of oncologic pain ranges from 33% in patients after curative treatment to 59% in patients undergoing antitumor therapies and can reach up to 64% in patients in advanced or terminal stages. Neuropathic pain in particular poses a challenge for palliative care specialists due to the non-specificity of its clinical features.

In non-oncologic neuropathic pain tricyclic antidepressants and antiepileptic medications are adjuvant drugs with strong evidence of efficacy. However the effectiveness of these drugs in oncology patients seems to be lower. Existing literature suggests that adjuvant medications are necessary for achieving adequate pain control when a neuropathic component is present but the evidence in this regard is limited. Tricyclic antidepressants are considered first-line therapy for non-oncologic neuropathic pain. The best available evidence also supports the use of gabapentin, while there is limited data on the efficacy and safety of pregabalin due to a lack of randomized controlled studies.

Objectives

The aim of this study was to assess the efficacy of amitriptyline, gabapentin and pregabalin in the management of neuropathic pain associated with cancer.

Methods

A retrospective observational study was conducted on oncology patients aged >18 years who had initiated palliative care in a residential or home-based setting from January 2023. These patients were already receiving opioid analgesic therapy. Exclusion criteria included a Karnofsky Performance Status (KPS) score <30 and a positive history of alcohol or substance abuse. The presence of neuropathic pain was initially assessed using the DN4 screening test for neuropathic pain. Patients were divided into 3 groups based on the adjuvant medication prescribed: gabapentin (Group G), pregabalin (Group P) or amitriptyline (Group A). Dosages were adjusted for each patient based on symptom control. Gabapentin dosages ranged from a minimum of 600 mg per day to a maximum of 1200 mg per day, divided into 2 or 3 daily doses. Pregabalin dosages ranged from a minimum of 25 mg per day to a maximum of 300 mg per day, administered once or twice daily. Amitriptyline dosages ranged from a minimum of 10 mg per day to a maximum of 30 mg per day, given as a single evening dose. Oral morphine was used as a rescue analgesic for persistent pain. Pain control was assessed weekly over a total duration of 4 weeks using the Numerical Rating Scale (NRS) for pain assessment. Adverse effects were also evaluated.

Results

34 patients were included in the study, with 9 receiving amitriptyline (Group A), 11 receiving gabapentin (Group G), and 14 receiving pregabalin (Group P). After the 4-week observation period, patients in the pregabalin group exhibited a greater reduction in pain compared to those in the other 2 groups. Additionally both gabapentin and pregabalin demonstrated a significant advantage over amitriptyline in terms of reducing the need for rescue morphine. The most commonly reported adverse effects were drowsiness and dry mouth but no cases required dosage reduction or treatment discontinuation.

Conclusions

The findings of this study indicate that all the medications investigated are effective in managing difficult cancer-related pain, specifically neuropathic pain. Moreover there is evidence to suggest that pregabalin, despite limited scientific support, may be more effective than gabapentin and amitriptyline as an adjuvant treatment for cancer-related neuropathic pain.