Brief report: case reports on naltrexone use in children with autism: controlled observations regarding benefits and practical issues of medication management.

Autism is a developmental disorder characterized by pervasive impairments in social interaction and communication, as well as restricted range of activities and interests. The prevalence of this neurobiologic disorder is currently estimated at 1;1000 (National Institutes of Health, 1995). Although the specific etiology for autism is unknown, it has been associated with other medical or genetic conditions in approximately 10% of cases (Bailey, Phillips, & Rutter, 1996; Rutter, Bailey, Button, & Le Couteur, 1994). Research emphasis has been on genetic, immunologic, metabolic, and neurochemical factors which may play a role in creating this spectrum disorder. Regardless of the etiology, autism has a tremendous impact on children and their families. Primary intervention for autism is currently educational and behavioral. However, medication may play an important role in the facilitation of learning and appropriate behavior. Naltrexone is a long-acting opioid antagonist proposed as an effective treatment for autism based on the theory of a dysfunctional endogenous opioid system in this disorder. Panksepp (1979) proposed that autism results from a failure of striatal beta endorphins to diminish with maturation. More recently, Chamberlain and Herman (1990) hypothesized a complex model involving dysfunction in brain melatonin, opioid precursors, and monoamines in autism. Limited objective support for endorphin dysfunction in autism has been evidenced by plasma and cerebrospinal fluid studies measuring beta endorphins in children with autism; these studies are summarized in an article by Gillberg (1995). Although the efficacy of naltrexone in the treatment of autism remains somewhat controversial, a majority of studies have indicated some beneficial effects of naltrexone in individuals with autism. Barrett, Feinstein, and Hole (1989), using a single-subject experimental design under double-blind, placebo-controlled conditions, showed a decrease in self-injurious behavior to near-zero rates for naltrexone versus naloxone. Campbell et al. (1993) studied 41 children and found significant reduction in hyperactivity but no effect on discrimination learning. Bouvard et al. (1995), in a double-blind study of 10 children with autism, demonstrated modest behavioral improvements which appeared to correlate with normalization of elevated plasma chemistries. Kolmen, Feldman, Harden, and Janosky (1997) reported the results of a double-blind, placebo-controlled crossover study and concluded that naltrexone was associated with modest improvement in behavior but no change in learning for 11 of the total 24 children studied. Willemson-Swinkels, Buitelaar, and Van Engeland (1996) completed a double-blind, placebo-controlled study of 23 children with autism in which teacher reports indicated a decrease in hyperactivity and irritability but no effect on social and stereotyped behaviors. A recent follow-up study by Willemson-Swinkels et al. (1999) indicated continued modest improvement in hyperactivity for 6 children who showed initial response to naltrexone and were monitored during a 6-month continuation treatment. Thus, previous studies have indicated that naltrexone has benefit in decreasing self-injurious behavior and hyperactivity. Indeed, Campbell (1996) has proposed that children with autism should be considered for a