Naltrexone and the Treatment of Autism

A paradigmatic example of a potentially useful neuropeptidergic intervention strategy (as well as the attending conceptual and pragmatic problems) can be highlighted by summarizing past attempts to utilize opiate antagonists in the treatment of autism. As already noted, the opioid linkage to autism was initially based on the striking similarities between classic autistic symptoms and those produced by injection of opioid drugs—including decreased separation distress, decreased gregariousness, decreased pain sensitivity, and increased stereotypies and rough-and-tumble play (Panksepp and Sahley, 1987).

After an initial flurry of small but promising open trials, the subsequent doubleblind, placebo-controlled trials have provided mixed evidence with the broad-spectrum opiate receptor antagonist naltrexone. Some have yielded modest benefits (e.g., Kol-men et al., 1997; Panksepp et al., 1991), especially on self-injurious behaviors and overactivity (Campbell and Harris, 1996). Subsequent trials, using rather high doses of naltrexone, yielded no benefits (Willemsen-Swinkels et al., 1996), but some have advocated the use of quite low doses infrequently (e.g., 0.25 mg/kg orally every other day) and have claimed that the quality of psychosocial contexts may be essential to support the social-motivational changes produced by naltrexone (Panksepp et al., 1991). Considering the biochemical evidence for abnormal opioid dynamics in the autistic brain and body (Bouvard et al., 1995; Gillberg, 1995) and the fact that subgroups of individuals with the most severe imbalances remain to be separately studied, clearly more research is needed not only with naltrexone, but also the more specific antagonists for the other opioid receptors. The pros and cons of evaluating every child with naltrexone have been aired, and there is only general agreement that the drug does reduce overactivity symptoms (Campbell and Harris, 1996).

In sum, the subset of children that do benefit remains hard to specify, but presumably those that exhibit an initial negative affective response, which may reflect an acute opioid withdrawal phenomenon, may be most likely to benefit with careful selection of doses (Panksepp et al., 1991). It should also be noted that dietary maneuvers (i.e., low-casein, low-gluten diets that can be sources of dietary opioids) that may have benefits by reducing opioid titers remain active areas of inquiry (Knivsberg et al., 2001, 2002).

There are a host of methodological concerns that need to be considered in future trials. First, autism is not a single brain disorder, and only a subset of children might respond to naltrexone. Thus, one should first aspire to identify drug responders and then to conduct double-blind studies on them to maximize the characterization of therapeutic trends. Further, since opiate antagonists can increase social motivation, the suggestion has been made that increased provisioning of socially sensitive and responsive environments may be important for obtaining optimal therapeutic effects. For naltrexone to work beneficially, caretakers may need to exhibit increased levels of social concern and reciprocity (Panksepp et al., 1991). If this proves to be the case in larger studies, it may highlight a new general principle of therapeutic efficacy alluded to above: Namely, certain neuropeptidergic agents that modulate specific emotional processes may need conjoint optimization of social-environmental and/or psychotherapeutic supports for maximal efficacy. So far, no neuropeptide modulator has been evaluated with such a principle in mind. Of course, the large number of therapeutic claims in the literature, especially in an area where placebo effects seem to be substantial, makes it difficult to sift substantive findings from type 1 errors (Hunsinger et al., 2000).

Funny Wiring Autism

Funny Wiring Autism

Autism is a developmental disorder that manifests itself in early childhood and affects the functioning of the brain, primarily in the areas of social interaction and communication. Children with autism look like other children but do not play or behave like other children. They must struggle daily to cope and connect with the world around them.

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