This invention relates to a sustained release oral and transdermal pharmaceutical formulations and delivery systems comprising lofexidine. The invention is also directed to methods of treatment comprising administering lofexidine in a sustained release manner. Such methods can involve administration of the lofexidine containing compositions described herein. Compositions of lofexidine formulated for sustained release delivery are provided. Also provided are methods for the treatment of opiate addicts, migraine, neuropathic pain, and other therapeutic indications related to lofexidine. The methods may provide treatment for a variety of conditions amenable to amelioration by lofexidine administration. The methods utilize lofexidine compositions formulated for transdermal and sustained release oral delivery for administration of lofexidine in an amount effective for the treatment of the drug indications.