Use of antipsychotics and psychostimulants for challenging behaviors in the intellectually disabled

Challenging behavior is a term often used in the field of the intellectually disabled (ID) to define a range of disruptive and dangerous actions.¹ Behaviors often referenced in this category include aggression, hyperactivity, impulsivity, self-injury, property destruction, and occasionally obsessive-compulsive behaviors.²³ These behaviors not only burden the individual but also increase strain on caregivers and impair social interactions. The incidence of disruptive behaviors and/or self-injury has been cited as occurring in 10–62% of individuals with ID, regardless of age, residing in institutions as well as in community settings.⁴ For children and adolescents with ID, the reported rate of impulsivity and aggression is about 20%.⁵ It should be noted both impulsivity and aggression often manifests earlier in individuals with ID than typically developing individuals. Psychotropics are used more frequently in the institutional settings, and adults are often prescribed psychotropic medications more often and at higher doses.⁴ Because of the persistent and prevalent nature of challenging behaviors, polypharmacy often becomes a factor during treatment; however, behavioral therapies should not be ignored. Due to longer periods of treatment, higher doses, and polypharmacy, individuals with ID may be predisposed to be the most overmedicated patient population.⁶

Psychotropics have a long history of being used in individuals with ID particularly for challenging or problematic behaviors. The rate at which these medications are being prescribed has been increasing over the past decade especially in mental health clinics and institutions. The prescribing rate of psychotropics for persons with ID is reported to be between 20–45% with 14–30% of patients receiving the medication to manage challenging behaviors.³⁴ Often psychiatric medications are prescribed in the absence of a diagnosed psychiatric disorder.⁷

Even across the age continuum, the medication treatment strategies for individuals with ID are relatively similar.⁴ The general mantra is “start low, go slow” when prescribing psychiatric medications in this patient population. Psychotropics are often used primarily to target challenging behaviors (e.g., aggression, impulsivity, self-injury, and property destruction). While all classes of psychotropics have been used to some extent in this group of individuals, up to two-thirds of individuals are prescribed antipsychotics with the shift from typicals to atypicals occurring within the past decade.⁸ In a survey conducted by Bramble, clinicians prescribed only one psychotropic in 71% of patients and two medications in 23% of patients.⁹ The most commonly prescribed combination cited was methylphenidate and risperidone.

Antipsychotics, particularly the atypicals, are probably the most frequently studied class of psychotropics in individuals with ID. While no antipsychotic is FDA approved for the treatment of challenging behaviors in ID, risperidone leads the pack both as the most studied and the most commonly prescribed antipsychotic for the treatment of challenging behaviors in this group of patients.³ A review of six studies concluded risperidone to be effective for the management of agitation and aggression not previously responding to non-pharmacologic interventions.¹⁰ This conclusion does not translate to all types of challenging behavior; such as self-injury. A recent meta-analysis identified three randomized, double-blind, placebo-controlled trials each with open-label extensions using risperidone for the management of problem behaviors in children and adolescents with an intelligence quotient (IQ) below 70.³

All six studies found a significant reduction in the Clinical Global Impressions (CGI) scale for the risperidone groups compared with the placebo group (p<0.05). In addition, a significant difference between the risperidone group and the placebo group was found on the Aberrant Behavior Checklist (ABC)–Irritability subscale (p<0.05) for five of the studies, while the remaining study found a significant difference from baseline to endpoint on the ABC scores within the risperidone group (p<0.05). Positive effects typically developed within the first two weeks of treatment initiation and were sustained for a long period of time.³

Adults, and especially children, with ID are often at increased risk of adverse effects even at low and typically prescribed doses.² In the setting of risperidone, several adverse effects need to be considered such as weight gain, somnolence, hyperprolactinemia, and increased extrapyramidal symptoms (EPS) especially at doses greater than 6 mg/day. It should be cautioned that the adverse effect of somnolence may compound the beneficial effects attributed to risperidone.³

Other atypical antipsychotics to mention include aripiprazole, olanzapine, quetiapine, and ziprasidone. Neither olanzapine nor quetiapine can be recommended as first-line agents based upon the results of open-label trials. While effective for hyperactivity and irritability olanzapine is not recommended mainly because of its adverse effect profile, particularly the increased risk of weight gain and hyperlipidemia.⁴ The open-label studies of quetiapine did not conclude it was effective for aggressive or hyperactive behavior and quetiapine was poorly tolerated.⁴ Aripiprazole has mainly been studied for irritability and aggression in the context of autism spectrum disorders (ASD). In the setting of ASDs, ID may occur across the entire spectrum with the exception of high-functioning autism. About 40% of patients with ASDs may exhibit severe mental retardation (MR), while mild MR may occur in up to 30% of individuals.⁴ Stingler et al. described five autistic patients during an open-label trial as improving on the CGI.¹¹ More studies are required before a definitive conclusion can be made for aripiprazole in this population. Ziprasidone, like aripiprazole, has only been studied in the pervasive developmental disorder (PDD) population. Decreased aggression and irritability were reported by McDougle et al. in a case series.¹² However, because of the lack of evidence and potential for QT-interval prolongation, ziprasidone is not recommended.

Whereas antipsychotics are the most commonly prescribed in children and adults with ID, attention deficit hyperactivity disorder (ADHD) is the most widely diagnosed psychiatric disorder. Prevalence rates can increase to between 8.7–16% among this population compared with 5% in typically developing individuals.² Methylphenidate is the most commonly prescribed psychostimulant in children and adolescents with ID. It is also the most frequently and thoroughly studied psychostimulant in this patient population. In a review of at least 20 previously published controlled studies, the response rates ranged from 45% to 66% in the ID population; however, this was still 10 to 30% lower than the typically developing group.² A meta-analysis of seven studies by Conner et al. indicated the effects of psychostimulants are as beneficial for aggression and aggression-related behaviors as for the core symptoms of ADHD, such as hyperactivity and impulsivity.¹³ Psychostimulants do not appear as effective for individuals with an IQ below 50 as positive responses decrease to less than 20%.¹⁴ Regardless of IQ, the rate of adverse effects tends to increase in individuals with ID even at smaller doses.

Many classes of psychotropic medications have been prescribed “off-label” for the use of challenging behaviors in individuals with ID. The atypical antipsychotics and psychostimulants, particularly risperidone and methylphenidate, have the most evidence with the majority of studies and case reports indicating beneficial effects and good tolerability. A few important points to remember when prescribing any medication in this patient population is that patients tend to respond to lower doses of medications and may be more susceptible to adverse effects even at lower doses. Further studies are required to determine the efficacy of additional psychiatric medications for the treatment of challenging behaviors for individuals with ID.