Montelukast Versus Gabapentin for Uremic Pruritus in Twice‐Weekly Hemodialysis Patients: A 52‐Week Prospective Non‐Randomized Open‐Label Comparative Study

ABSTRACT Background Uremic pruritus (UP) remains a common and distressing complication in patients with end‐stage renal disease (ESRD) receiving maintenance hemodialysis. The burden is particularly pronounced in low‐ and middle‐income countries where twice‐weekly hemodialysis is frequently practiced because of resource limitations. Gabapentin is widely used for the treatment of uremic pruritus; however, its use is often limited by central nervous system adverse effects and poor tolerability in older dialysis populations. Montelukast, a leukotriene receptor antagonist with anti‐inflammatory properties, has been proposed as a potential alternative therapy. This study aimed to evaluate the comparative efficacy and safety of montelukast versus gabapentin for the treatment of uremic pruritus in patients receiving twice‐weekly hemodialysis, with extended follow‐up over 52 weeks. Methods This prospective, open‐label, non‐randomized comparative study enrolled 195 adult patients with refractory uremic pruritus receiving twice‐weekly hemodialysis. Participants were allocated to receive either montelukast or gabapentin based on predefined clinical and demographic criteria, including physician discretion and patient‐specific factors. Clinical follow‐up was conducted at 2, 4, 8, 12, 24, and 52 weeks. Pruritus severity was assessed using the Visual Analogue Scale (VAS). The primary outcome was change in Visual Analogue Scale score from baseline. Secondary outcomes included adverse events, treatment tolerability, need for dose escalation, and treatment discontinuation. Results A total of 176 patients completed the 52‐week follow‐up (montelukast, n  = 91; gabapentin, n  = 85). Baseline pruritus severity was comparable between the montelukast and gabapentin groups (mean VAS score 7.26 ± 1.56 vs. 7.41 ± 1.67, p  = 0.54). Both treatments produced significant reductions in Visual Analogue Scale scores from baseline throughout the 52‐week follow‐up ( p  < 0.001 for both groups). Dose escalation was required in 38 patients (44.7%) receiving gabapentin within the first 6 weeks of therapy. Adverse events occurred significantly more frequently in the gabapentin group than in the montelukast group; 6 histories of falls and 11 treatment discontinuations due to adverse effects. Frequent adverse events reported in the montelukast group were abdominal pain and headache (17 and 14 episodes, respectively); whereas in the gabapentin group the common side effects were somnolence (39 incidence), fatigue ( n  = 21), dizziness ( n  = 17), and cognitive slowing ( n  = 16). Although gabapentin achieved modestly greater reductions in Visual Analogue Scale scores at selected follow‐up time points, the absolute between‐group differences remained below the predefined minimum clinically important difference of 1.0 VAS point. Conclusions Montelukast provided sustained clinically meaningful improvement in uremic pruritus with substantially fewer treatment‐related adverse events and superior tolerability than gabapentin. Although gabapentin achieved slightly greater reductions in pruritus severity at selected time points, these differences did not exceed the predefined minimum clinically important difference of 1.0 VAS point. Montelukast represents a practical and well‐tolerated therapeutic option for patients receiving twice‐weekly hemodialysis, particularly in resource‐limited settings.