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CHRONIC USE OF OPIOIDS AND ANTIPSYCHOTIC DRUGS: SIDE EFFECTS, EFFECTS ON ENDOGENOUS OPIOIDS, AND TOXICITY *

There is increasing enthusiasm, supported both by anecdotal clinical observations and various pieces of scientific information, to consider the use of natural opiates or opioids, including narcotic drugs, endogenous opioid peptides, and their synthetic congeners, in the management of specific types of psychiatric disorders. It is essential to identify the potential risks of such treatment, and to compare these risks with those encountered during chronic treatment with clinically accepted agents. Potential “risks” of a therapeutic agent such as opioids include undesirable side effects, alterations of normal physiological function, including alterations in hormonal levels, adverse reactions, and also direct drug toxicity. The side effects, the interactions with endogenous opioids, and the toxicity of opioids, antipsychotic agents, and antidepressant drugs will be the topic of this discussion. However, another area of potential risk, not to be discussed in detail, but clearly relevant to chronic opioid use, is the predictable development of tolerance to physical dependence on the drug, which may be related to the subsequent development of addiction. There is also the potential risk that any perturbation in normal physiology that might occur during chronic treatment with an opioid might return to normal very slowly or even be irreversible following cessation of treatment, and that these alterations might, in fact, be related to the processes of tolerance, dependence, and addiction. Tolerance, physical dependence, and addiction do not develop during chronic treatment with most of the antipsychotic or antidepressant drugs currently used for the management of the specific psychiatric disorders that might alternatively (or more successfully) be managed by chronic opioid treatment. If an opioid were found to be very effective in the management of any specific disorder, and if chronic treatment were indicated, the development of tolerance and physical dependence might not be considered to be major risks. “Addiction” would not be recognized unless treatment were discontinued. However, potential problems related to the development of tolerance, dependence, and addiction must be carefully considered prior to instituting shortor long-term treatment with opioids. Information concerning the side effects, adverse reactions, and toxicity of any drug is often fragmentary. Many side effects of chronic usage of a drug do not appear until after years of treatment, and a large number of patients under treatment is required to detect side effects of low or moderate frequency in their occurrence. Some so-called “side effects” of drugs are really well-known