December 18, 1998

The results of the first open-label study of the atypical neuroleptic drug risperidone in children and adolescents with post-traumatic stress disorder (PTSD) show it improves severe symptoms.

Principal investigator Joseph Horrigan, M.D., presented the findings at the American Academy of Child and Adolescent Psychiatry meeting in October in Anaheim, Calif.

"The goal of the study was to investigate whether atypical neuroleptics especially risperidone, might have a role in the management of severe PTSD in children, which is characterized by aggressive and disruptive behaviors including hyperactivity and low frustration tolerance. Moreover, traditional agents such as alpha 2 agonists, anticonvulsants, tricyclics, and SSRIs have not been effective in treating severely traumatized children," said Horrigan, an assistant professor of psychiatry at the University of North Carolina at Chapel Hill.

A typical neuroleptics may also cause less cognitive dulling than typical neuroleptics as well as improve attention and concentration, which would benefit children and adolescents in academic settings, added Horrigan.

The results of his 16-week trial in 18 boys with severe PTSD treated with risperidone showed significant improvement in 50 percent of them, moderate improvement in 22 percent, and mild improvement in 11 percent on the Clinical Global Impression Scale. There was no improvement in 17 percent. Subjects were enrolled in the residential treatment center in Durham, N.C. The starting and modal dose of risperidone was 0.5 mg twice a day with the average dose being 1.3 mg daily. This is consistent with the literature, which suggests a range between 1 mg and 3 mg for children and between 3 mg and 6 mg for adults regardless of diagnoses.

Horrigan noted that higher doses of risperidone could induce extrapyramidal symptoms (EPS) such as dystonia and akinesia.

He also found a significant improvement in the pre-trial and post-trial scores on the Conners Abbreviated Teachers Ratings Scale with a mean decrease of 10 points. The scale measures behaviors commonly associated with ADHD such as impulsivity and temper tantrums.

There were no acute or chronic side effects during the trial, noted Horrigan. "Risperidone appears to be well tolerated in treatment-resistant patients and reduces positive symptoms associated with PTSD such as hypervigilance, nightmares, and flashbacks." He also recommended that risperidone be tapered when ending a trial rather than abruptly discontinued.

All 18 patients in the trial met the diagnosis for severe PTSD. In addition, 83 percent met the criteria for comorbid ADHD, 56 percent for oppositional/defiant disorder, 33 percent for bipolar disorder, 22 percent for conduct disorder, 11 percent for psychosis, and 11 percent for major depression.

This population may also be "traumagenic" because of the high incidence of physical abuse (14 patients) and sexual abuse (8 patients) suffered at the hands of their caretakers, said Horrigan. The reason may be that the "intensity of the patient's mood and behavior problems elicits strong inappropriate responses from caregivers."

Because patients with severe PTSD have high rates of comorbidity, Horrigan uses a triple drug therapy in his clinical practice. The combination includes a psycho-stimulant, mood stabilizer, and alpha 2 agonist such as clonidine. "If the alpha 2 agonist fails to hold the child together, I try an atypical neuroleptic."

Horrigan explained that he doesn't use atypical neuroleptics first because "they are still relatively new agents (risperidone was approved by the FDA in 1994) and have not been approved for pediatric indications. Moreover, controlled studies of the drug are lacking in children."

"The open-label pilot study is the first step in defining the clinical application of atypical neuroleptics in severely traumatized children and adolescents," said Horrigan.

Rigorous placebo-controlled studies are needed in multiple sites to examine the efficacy and safety profile of risperidone and other atypical neuroleptics including olanzapine and quetiapine, he noted.