Risperidone Treatment in 12 Children With Developmental Disorders and Attention-Deficit/Hyperactivity Disorder

Abstract

Background: Risperidone is a novel antipsychotic drug that has been tried in the treatment of several child psychiatric disorders. In an open clinical study, we evaluated the safety and efficacy of risperidone in children with developmental disorder and behavioral problems including attention-deficit/hyperactivity disorder (ADHD).

Method: Twelve patients aged 4 to 14 years who had a DSM-IV–diagnosed developmental disorder and ADHD in addition to other behavioral problems, in particular aggression, were treated with risperidone for a period of up to 2 years with daily doses ranging from 1 to 3 mg. Data were gathered from December 2002 to December 2004.

Results: A positive clinical response was noted in 9 of the 12 patients within 3 months of study recruitment according to the Clinical Global Impressions-Improvement scale. Risperidone was well tolerated by all 12 patients. The most commonly reported side effect was sedation, which necessitated dosage reduction in 2 patients, but not discontinuation.

Conclusions: Our findings suggest that risperidone may be an effective and safe treatment for children and adolescents with developmental disorder and disruptive behaviors.

Behavioral problems often coexist with developmental and learning disorders, and in these instances, irritability, aggression, hyperactivity, insomnia, and self-injurious behaviors are the main features. Reports have been published indicating that risperidone is effective in treating behavioral problems in patients with mental retardation^1,2 and developmental disabilities^3,4 and in children with autism and other pervasive developmental disorders.^5–8 A large double-blind, placebo-controlled study⁶ of risperidone for the treatment of autism and serious behavioral disorders published recently showed the efficacy of the drug in the treatment of tantrums, aggression, and self-injurious behavior in children with these disorders. A few other reports have suggested its usefulness in children with a wide range of behavioral problems, including aggression and self-injurious behaviors,¹ aberrant behaviors,⁹ pathologic aggression,¹⁰ explosive aggressive autism,¹¹ and comorbid attention-deficit/ hyperactivity disorder (ADHD) and conduct disorder,¹² as well as aggressive behavior in the context of mood disorders.¹³ This article reports on the open clinical experience of treating with risperidone 12 children who had a developmental disorder and comorbid ADHD.

PATIENTS AND METHODS

In this series of 12 patients, the subjects' ages ranged from 4 to 14 years (mean = 7.5 years, SD = 3.513); all patients were male with the exception of 1. All of the patients referred to the child psychiatry and neurodevelopmental clinics from the primary health and school health clinics for the Al Ain Medical District of United Arab Emirates over a period of 1 year were included in the study. Informed consent was obtained from the patients' guardians, and Declaration of Helsinki guidelines were followed. Assessments were made at the University Teaching Hospital clinics. Data were gathered from December 2002 to December 2004.

All of the children were evaluated by a child psychiatrist, and diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).¹⁴ A checklist based on the DSM-IV criteria was used, and corroborative information was obtained using the Arabic version of the Conners' Parent Rating Scale or Conners' Teacher Rating Scale¹⁵ during the initial evaluation. ADHD was present in all of the patients (8 had the “combined” subtype and 4 had the “hyperactive” subtype of ADHD) in addition to other disruptive behaviors (Table 1). The children reported here were clinically heterogeneous, with different DSM-IV diagnoses (see Table 1), but they all had a developmental disorder (6 had mental retardation, 4 had pervasive developmental disorder, and 2 had communication disorder).

Table 1.

Characteristics of Children With Developmental Disorders and Disruptive Behaviors Treated With Risperidone

Risperidone treatment was started in doses of 0.5 mg once daily and increased gradually (in increments of 0.5 mg per month) to a maximum of 3 mg per day. Clinical efficacy was assessed on a monthly basis using the Clinical Global Impressions-Improvement scale (CGI-I),¹⁶ and parents were prompted to report commonly observed side effects such as sedation, weight or appetite changes, tiredness, and extrapyramidal side effects.

RESULTS

Clinical improvement was noted in 9 patients within 3 months of recruitment into the study (Table 1): scores on the CGI-I indicated mild improvement (score of +1) in 2 patients (cases 3, 6), moderate improvement (score of +2) in 5 (cases 1, 5, 8, 11, 12), significant improvement (score of +3) in 2 (cases 7, 10), and no change (score of 0) in 1 (case 9). Symptoms were reported to be worse (score of −1) in 1 patient (case 2) and much worse (score of −2) in another (case 4). Mean CGI-I score was 1.25 (SD = 1.545). Risperidone was effective in improving ADHD, aggression, and self-injurious behaviors. Sedation was reported in 2 patients, necessitating reduction in dosage but not discontinuation. The other side effects reported included tiredness and weight gain. No patients experienced extrapyramidal symptoms. Those who showed a positive clinical response were followed up for periods ranging from 12 to 23 months.

DISCUSSION

Although psychostimulants remain the mainstay of pharmacologic treatment for ADHD, they may not be tolerated by some children, may be ineffective in some, and in yet others may exacerbate a comorbid medical condition such as seizures or tics. Furthermore, most of the conventional antipsychotics used in these situations do not combat persistent irritability, extreme aggression, and other maladaptive behaviors, which often coexist in children with developmental disorders. In our cohort, risperidone was also used for different reasons including concern about the epileptogenic potential of certain drugs in the context of nonspecific electroencephalographic changes, precipitation of tics with methylphenidate, and undesirable side effects or poor response to alternative pharmacologic interventions.

Risperidone has been noted to be useful for insomnia in pervasive developmental disorder¹⁷ and for behavioral problems in developmentally disabled children¹⁸ and in adults with profound retardation and autism.¹⁹ Our findings that risperidone was effective in improving ADHD, aggression, and self-injurious behaviors suggest that risperidone has promise for the treatment of children with developmental disorders and disruptive behaviors. Furthermore, there was improvement in coexisting sleep and appetite problems. The drug was well tolerated by the children in the dosages used (1–3 mg). The most common side effect reported was sedation in 2 patients, followed by tiredness and weight gain in 1 patient each. Earlier studies have reported weight gain,²⁰ chorea and dyskinesia,²¹ reversible withdrawal dyskinesia,²² and facial dystonia and amenorrhea²³ with the use of risperidone. However, in a study by Simon and colleagues,²⁴ traditional antipsychotics were substituted with risperidone in 10 individuals with mental retardation, and all participants evidenced improvement or resolution in side effects attributed to previous antipsychotic medication, with no worsening in behavioral or psychiatric status. Furthermore, Zuddas et al.²³ and Croonenberghs et al.²⁵ observed in their 1-year follow-up studies that risperidone is relatively safe for long-term treatment of behavioral problems.

In this study, risperidone was used for periods of up to 2 years with no undesirable effects. Because it is the usual clinical practice that children who show short-term benefit from a drug will be maintained on treatment with the medication indefinitely, it is important to evaluate the longer-term effectiveness and safety of risperidone in this population.

Drug names: carbamazepine (Carbatrol, Equetro, and others), chlor-promazine (Thorazine, Sonazine, and others), clonazepam (Klonopin and others), clonidine (Catapres, Duraclon, and others), fluoxetine (Prozac and others), haloperidol (Haldol and others), methylphenidate (Ritalin, Metadate, and others), risperidone (Risperdal).