Objective(s): Comparative in vivo studies were carried out to determine the adsorption characteristics of amitriptyline (AMT) on activated charcoal (AC) and sodium polystyrene sulfonate (SPS). AC has been long used as gastric decontamination agent for tricyclic antidepressants and SPS has showed to be highly effective on in-vitro drugs adsorption. Materials and Methods: Sprague-Dawley male rats were divided into six groups. Group I: control, group II: AMT 200 mg/kg as single dose orally, group III and IV: AC 1g/kg as single dose orally 5 and 30 min after AMT administration respectively, and group 5 and 6: SPS 1 g/kg as single dose orally 5 and 30 min after AMT administration, respectively. 60 min after oral administration of AMT (Tmax of AMT determined in rats), Cmax plasma levels were determined by a validated GC-Mass method. Results: The Cmax values for groups II to IV were determined as 1.1, 0.5, 0.6, 0.1 and 0.3 µg/ml, respectively. Conclusion: AC and SPS could significantly reduce Cmax of AMT when administrated either 5 or 30 min after AMT overdose (P