Methods for overcoming resistance to tramadol

A method for treating a disorder modulated at least in part by opiate receptor activity or monoamine activity, comprising orally administering every six hours to a subject in need thereof a pharmaceutical composition consisting of a therapeutically effective amount of an active pharmaceutical ingredient and pharmaceutically acceptable carriers in a sustained release dosage form, wherein the active pharmaceutical ingredient consists of O-desmethyltramadol (M1), or a pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable carriers consist of a polymer selected from polysaccharide, acrylic resin, polyalkylene glycol, polyvinyl acetate, polyvinylpyrrolidone, protein-derived materials, colloidal silica, and mixtures thereof, microcrystalline cellulose;

• and, optionally, one or more pharmaceutical excipients selected from the group consisting of preservatives, buffers, salts and magnesium stearate;
• and wherein the mean difference between minimum and maximum plasma concentration of M1 at steady state (ΔCss) is not more than 40 ng/ml.