Compositions and methods for overcoming resistance to tramadol

A sustained release dosage form, comprising a therapeutically effective amount of O-desmethyltramadol, or a pharmaceutically acceptable salt thereof, and pharmaceutical excipients;

• wherein the sustained release dosage form comprises a matrix, reservoir, coated-bead or multi-particulate;
• wherein the sustained release oral dosage form has a dissolution rate consisting of
• between 15 and 74% O-desmethyltramadol released at 1 hour,
• between 28 and 91% O-desmethyltramadol released at 2 hours,
• between 38 and 101% O-desmethyltramadol released at 3 hours,
• between 47 and 105% O-desmethyltramadol released at 4 hours,
• between 59 and 105% O-desmethyltramadol released at 6 hours,
• between 68 and 105% O-desmethyltramadol released at 8 hours,
• between 75 and 105% O-desmethyltramadol released at 10 hours,
• between 79 and 105% O-desmethyltramadol released at 12 hours,
• 100% O-desmethyltramadol released at 24 hours, by weight;
• and
• wherein upon administration to a human subject delivers O-desmethyltramadol with a difference between minimum and maximum plasma concentration of O-desmethyltramadol at steady state is not more than 40 ng/mL.