Banerjee, M., Pal, S., Bhattacharya, B., Ghosh, B., Mondal, S., & Basu, J. (2013). A comparative study of efficacy and safety of gabapentin versus amitriptyline as coanalgesics in patients receiving opioid analgesics for neuropathic pain in malignancy. Indian Journal of Pharmacology, 45, 334–338.

To determine the comparative efficacy and safety of gabapentin and amitriptyline as coanalgesics for cancer-related pain

Patients were assigned randomly to receive oral tramadol 150–200 mg and oral gabapentin titrated from 600–1,800 mg daily, or tramadol 150–200 mg and amitriptyline titrated from 25–100 mg daily. Oral morphine or fentanyl transdermal patch were used as rescue medication. At baseline, if patients were on any coanalgesic, they were entered after a washout period. Patients were followed monthly up to six months. Patients were asked to maintain a diary used for assessment of compliance. Once a patient used rescue medication, the patient was excluded from further efficacy assessment, and last pain scores were carried forward.

• N = 76  
• MALES: 53%, FEMALES: 47%
• KEY DISEASE CHARACTERISTICS: Tumor types are not stated. Baseline pain scores were 8.425 on average.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients did not have any disorder of vital organs or bone marrow.

• SITE: Single site   
• SETTING TYPE: Outpatient   
• LOCATION: India

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

• Open-label, two-group, randomized trial

• Visual analog scale (VAS)—scored as 0, 1, or 2 if scores decreased, remained the same, or increased
• Verbal rating scale (VRS)
• Percentage of pain relief (PPR) calculated
• Global pain score calculated as the sum of changes in VAS score, VRS score, and PPR
• MD global impression of efficacy (four-point scale)

For patients receiving gabapentin, pain scores on the VAS reduced significantly between the first and second month (p < .001). The same timing and pattern of pain reduction were shown in the amitriptyline group (p < .001). No significant differences were seen between groups at any study time point. Six patients on gabapentin and eight patients receiving amitriptyline required rescue medication. Thirty percent of patients in the gabapentin group and 42% of patients in the amitriptyline group had adverse events. These were generally mild. More patients receiving amitriptyline experienced postural hypotension (p = .02) and dry mouth (p = .04). Sedation, dizziness, and dyspepsia were the most frequent side effects.

Findings suggest that gabapentin and amitriptyline can be effective as coanalgesics for neuropathic pain.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Findings not generalizable
• Subject withdrawals 10% or more
• Other limitations/explanation: Information regarding any changes in opioid medications or lack of change is not provided. No data regarding compliance are provided. Depending on the timing in which patients who used rescue medication had prior pain scores carried forward, this approach could have overestimated or underestimated results. Opioid dosage information is not provided. The sample did not appear to have any significant comorbid conditions, so applicability among patients with other chronic diseases is unclear.

Findings suggest that either gabapentin or amitriptyline can be effective coanalgesics for neuropathic pain, and professional guidelines generally have suggested consideration of such medication. The side effect profiles of the two drugs studied here were slightly different, so individual patient characteristics and risks need to be considered in medication selection. In this study, patients had no significant other disorders, so if similar results would be seen among patients with comorbid conditions is not clear.