Once daily baclofen sustained release or gastro-retentive system are acceptable alternatives to thrice daily baclofen immediate release at same daily dosage in patients

Abstract

Baclofen, a GABA-agonist, is currently available as an immediate release (IR) formulation for relieving neurogenic spasticity in a variety of disorders. Baclofen IR requires to be administered three times a day which inadvertently increases the chances of medication noncompliance among patients and is also associated with side effects such as drowsiness and muscle weakness. To overcome the shortcomings of baclofen IR, two modified formulations, baclofen sustained release (SR) and gastric retentive system (GRS), have been proposed to be equivalent in efficacy to baclofen IR with the administration of a single daily dose. Ninety patients with chronic neurogenic muscular spasticity were enrolled requiring 10-20 mg of baclofen IR every eight hours. The patients were randomized to two treatment arms: SR (n = 46) or GRS (n = 44) at the same once-daily dose for four weeks. Efficacy was measured by Ashworth score for muscle tone, spasm score, reflex score, 30-item functional independence score, and patient's diary score for three most affected activities of daily life. The mean Ashworth score changed significantly (P = 0.00) for patients in the SR group from 3.03-2.69 (-0.35) and 3.07-2.70 (-0.37) for patients in the GRS group. There was no significant difference (P = 0.87) between baseline-adjusted Ashworth score reductions on SR (-0.35) and GRS (-0.37). Similar results were obtained for spasm, reflex, and functional independence scores. The mean baseline-adjusted patient-diary scores did not differ significantly between 8 am, 12 pm, 4 pm, and 8 pm (P = 0.96), either on SR (-5.3 to -6.1) or GRS (-7.3 to -8.1), indicating a uniform effect round-the-day on both. Further, sedation scores (mean +/- SEM) decreased significantly (P < 0.05) on both SR (10.36 +/- 1.37 to 6.18 +/- 0.92) and GRS (8.14 +/- 1.57 to 5.33 +/- 1.11), suggesting better toleration. Once-daily baclofen SR and GRS are efficacious, convenient, and better-tolerated alternatives to baclofen IR in patients with neurogenic spasticity.