ary prevention, respectively). Particular attention is given to safety considerations of immunotherapies and depot medications, recognizing that some patients will continue to abuse various psychoactive substances and that these medications may be administered to pregnant women, adolescents, or children.

The FDA clinical trials process is designed to ensure safety and efficacy for specific uses or indications for new medications but not for off-label use in new diseases or in patient populations in which the medication was never studied. This appendix reviews the four phases of the FDA clinical trials process as it is likely to be implemented for the immunotherapies and depot medications currently in clinical or preclinical development. These products include depot formulations of naltrexone for alcohol and, potentially, opioid dependence; vaccination for cocaine and nicotine dependence; and monoclonal antibodies for phencyclidine (PCP), methamphetamine, and possibly cocaine. Also reviewed are the three types of treatment protocols: overdose, relapse prevention, and protection. Overall, the purpose here is to consider what might be learned during the FDA clinical trials process to inform later applications of these therapies and postmarketing experience. The surveillance that is an intrinsic part of the postmarketing experience should help to discourage premature examination of applications that may place certain populations at unacceptable risk.


The three types of treatment protocols—overdose, relapse prevention, and protection—are most suitably tested with different types of medication approaches: active immunization, passive immunization with monoclonal antibodies, or depot medications (Klein, 1998; Blaine et al., 1994). For example, overdose protocols most usefully employ monoclonal antibodies (passive immunization), while active immunization and depot medications have, at most, a limited role for this indication. Relapse prevention protocols can usefully employ any of these medication approaches, but different limitations exist for each approach. Protection protocols are the most speculative at present but could also use any of these three approaches. However, protection protocols must consider medical safety and frequency of administration as critical issues, since the individuals intended to benefit from these treatments do not require treatment for substance dependence. In addition, not all of the three types of intervention protocols are applicable to every abused substance. Overdose and relapse prevention protocols are very likely to be studied before these agents are approved for protection, but a protocol for protection from addiction is not likely to get controlled study because of several prac-

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