There are three opioid maintenance treatment medications currently available and used with some regularity: methadone (a full opioid agonist), buprenorphine (an opioid mixed partial agonist-antagonist), and naltrexone (an opioid antagonist). Each has been shown in controlled clinical trials to have efficacy for the treatment of opioid dependence. However, while efficacy is a key consideration when evaluating medications, decisions about the suitability of a medication rest upon an assessment of the balance between safety and efficacy. As there are more options in opioid treatment medications, comparisons between medications with respect to safety become more salient.

The safety of a medication can be viewed as consisting of both side effects (relatively minor to moderate non-therapeutic effects of the medication that are seen as troubling to the patient or clinician), and significant adverse events (effects of a medication that may be or are harmful to the patient and necessitate a change in how the medication is used). Medications can produce side effects and significant adverse events through direct action, and can also produce such effects through interactions with drugs, medications, or other intervening conditions.

With respect to the three commonly available opioid treatment medications, side effects and adverse events have been noted but in most cases not thought to be of high clinical significance. However, potential side effects or significant adverse events for these medications can become more clinically relevant, for example, as patients age or are treated with other medications. Awareness of these risks and the relative importance of these aspects of safety relative to efficacy are important for the clinician. Continued research to determine the safety of medications, especially for special populations (e.g., older patients), when used with other medications, or in the patients with other illnesses, is needed.