Article AbstractLetter to the Editor Sir: We appreciate the opportunity to reply to the insightful comments of Drs. Khantzian and Albanese regarding the selfmedication hypothesis and our recent findings published in August 2008. We acknowledge that addiction etiology includes a domain of psychologically distressing subjective factors such as problems regulating self-esteem, relationships, and self-care, as stated by Khantzian and Albanese. Nejtek et al. used DSM-IV criteria for all subjects. Substance "dependence" includes persistent psychological problems and impaired social, occupational, and/or interpersonal functioning. DSM-IV criteria for bipolar disorder suggest a level of severity causing "marked impairment" evident in depressive and manic symptoms such as psychomotor agitation, sleep disturbances, excessive positive or negative self-worth, or irritability creating an "unequivocal and uncharacteristic change in functioning that is observed by others."