Psychopharmacology notes: Pharmacotherapy in children and adolescents with pervasive developmental disorders

Journal of Child and Adolescent Psychiatric Nursing, Jan-Mar 1999 by Scahill, Lawrence, Koenig, Kathleen

Pervasive developmental disorders (PDDs) are a group of conditions characterized by impaired socialization and communication. Deficits in cognitive functioning and motor coordination also can be a part of the clinical picture. Recent developments in assessment and diagnosis of PDDs have helped delineate autism, Asperger's syndrome, childhood disintegrative disorder, Rett's syndrome, and pervasive developmental disorder-not otherwise specified (PDD-NOS) (American Psychiatric Association, 1994). Autism is a severe form of PDD that affects 3 to 5 children per 10,000 in the general population (Bryson, 1997). It is characterized by profound impairments in communication, social reciprocity, and stereotypes. Children with other PDDs, such as PDDNOS, may have autisticlike features, but may not have the same degree of impairment in social relatedness and communication seen in autism. Because it is a heterogeneous group and because the definition of PDD-NOS has recently been revised, the prevalence of PDD-NOS is not well established.

In addition to the core symptoms of delayed communication and socialization problems, children with PDDs may present with a range of problems. The symptoms most likely to prompt pharmacological intervention are aggression toward self or others, agitation, perseverative behavior, hyperactivity, or stereotypes. Target symptoms guide the choice of medication. No particular medication can effectively treat all the symptoms that may be manifested in a child with PDD. Several pharmacological agents (e.g., stimulants, neuroleptics, tricyclic antidepressants, serotonin reuptake inhibitors, clonidine, naltrexone) have been studied in children with PDD. This paper reviews the most effective medications in the treatment of PDD and offers guidelines for initiating a trial of selected medications.

Stimulants, clonidine, and naltrexone have shown limited usefulness in the treatment of PDD with mixed results. One study of methylphenidate described improvement in hyperactivity in children with PPD (Quintana et al., 1995). Increases in mood lability and negative behavior also have been reported (Strayhorn, Rapp, Donina, & Strain, 1988).

A double-blind study using clonidine showed a modest improvement in irritability and hyperactivity, but these beneficial effects tended to wane over time (Jaselskis et al., 1992). Studies of naltrexone in children with autism showed a decrease in overall severity, but no change in problem behaviors such as hyperactivity, selfinjurious behavior, or stereotypies (Campbell et al., 1990; Campbell et al.,1993).

Fenfluramine, an indirect serotonin receptor agonist, showed promise in early trials (Ritvo et al., 1984). Subsequent research, however, showed no differences between fenfluramine and placebo on the core symptoms of autism. In addition, recent data suggesting possible neurotoxicity from fenfluramine has caused declining interest in the drug (McDougle,1997).

Other medications that have shown benefit for the treatment of PDD include the tricyclic antidepressant clomipramine; the selective serotonin reuptake inhibitors (SSRIs) fluvoxamine, sertraline, and fluoxetine; and the typical neuroleptic haloperidol. Preliminary results also suggest that the atypical neuroleptic respiridone also may be useful.

In both open and double-blind studies, domi-pramine has been efficacious in reducing the core symptoms of autism, as well as in decreasing anger and uncooperative behavior (Gordon, State, Nelson, Hamburger, & Rappoport, 1993). Clomipramine is typically started at 25 mg/day with increases every 5 to 7 days as tolerated to a range of 100 to 250 mg/day. As with the other tricyclics, anticholinergic side effects are common. Other issues with clomipramine include the need for ECG monitoring (Scahill & Lynch, 1994), the lowering of seizure threshold (Gordon et al.), and the potential for drug interactions.

The SSRIs fluoxetine and fluvoxamine have showed promising results in the treatment of autism (Cook, Rowlett, Jaselskis, & Leventhal, 1992; McDougle et al., 1996). The results of these studies, however, suggest the SSRIs may not be as effective in children. As in other pediatric populations, children with PDD appear to be more likely than adults to exhibit restlessness, anxiety, agitation, and insomnia (McDougle, 1997; Scahill, 1996). Thus, SSRIs should start with low doses that are increased gradually. For an adequate trial, children should be maintained on the maximum, tolerable dose of an SSRI for at least 8 weeks.

Neuroleptics have been used cautiously in children with PDD due to concerns about side effects and possible long-term adverse effects (Campbell et al., 1997). Extrapyramidal symptoms such as dystonia, akathisia, parkinsonism, and tardive dyskinesia are well-known side effects of typical neuroleptics such as haloperidol. Despite these concerns, haloperidol has shown positive results for symptoms of aggression, stereotypies, and hyperactivity (Anderson et al., 1989). Other traditional neuroleptics have been studied, but most of these trials have been small open-label studies.