Methods for overcoming resistance to tramadol

A method for treating pain in a subject who is a poor metabolizer or ultra-rapid metabolizer of tramadol or shows tramadol analgesia, comprising administering to a subject in need thereof a sustained release dosage form consisting of a therapeutically effective amount of O-desmethyltramadol, or a pharmaceutically acceptable salt thereof, 1-40 wt %, and pharmaceutical excipients, 10-90 wt %;

• wherein the O-desmethyltramadol is (1S, 2S)—O-desmethyltramadol or a combination of both (1R, 2R)—O-desmethyltramadol and (1S, 2S)—O-desmethyltramadol wherein the excipients consist of one or more polymers selected from polysaccharide, acrylic resin, polyalkylene glycol, polyvinyl acetate, polyvinylpyrrolidone, protein-derived materials, and microcrystalline cellulose;
• a buffer;
• and, optionally, talc, colloidal silica, and/or magnesium stearate;
• and wherein the sustained release dosage form produces a plasma profile of O-desmethyltramadol that substantially replicates the plasma profile of O-desmethyltramadol following administration of tramadol.

A method for treating disorders modulated at least in part by opiate receptor activity or monoamine activity, comprising orally administering to a subject in need thereof a sustained release dosage form consisting of pharmaceutical excipients, 10-90 wt %, and a therapeutically effective amount of O-desmethyltramadol, or a pharmaceutically acceptable salt thereof, 1-40 wt %;

• wherein the excipients consist of one or more polymers selected from polysaccharide, acrylic resin, polyalkylene glycol, polyvinyl acetate, polyvinylpyrrolidone, protein-derived materials, and microcrystalline cellulose;
• a buffer;
• and, optionally, talc, colloidal silica, and/or magnesium stearate;
• and wherein the sustained release dosage form produces a plasma profile of O-desmethyltramadol that substantially replicates the plasma profile of O-desmethyltramadol following administration of tramadol.