Abstract
To The Editor:
T
Case Report
A 20-month-old male patient was diagnosed with ASD at another center and was included in the rehabilitation program. At the age 23 months, the patient's existing irritability and hyperactivity symptoms worsened; therefore, he was admitted to our clinic. After a “risk and benefits” ratio evaluation, it was decided to start pharmacological treatment. The body weight of the patient was 13.2 kg. Therefore, a starting risperidone dose (0.25 mg/day [0.019 mg/kg]) was initiated and controlled, while a dose increase was planned. On the 3rd day of treatment, a spasm in the jaws, neck, and back was observed, and we requested a pediatric neurology consultation. The cause was determined to be extrapyramidal side effects. It was thought to be associated with risperidone and therefore, risperidone was discontinued. Immediately, aripiprazole was started (1 mg/day [0.08 mg/kg]). The dose of aripiprazole was increased every two weeks until it reached 3 mg/day (0.22 mg/kg). During the follow-up, the patient was clinically evaluated by using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC)-Irritability and Hyperactivity subscales, Clinical Global Impressions-Severity (CGI-S) Scale, and Clinical Global Impressions-Improvement (CGI-I) Scale in 2 week intervals. The CGI evaluation was based on behavioral symptoms such as irritability and hyperactivity. At the time of admission, the patient's scale scores were as follows: CARS = 39, ABC-irritability = 30, ABC-hyperactivity = 39, and CGI-S = 5 (markedly ill). By the end of the 16-week-long treatment, the patient showed significant improvements in irritability and hyperactivity symptoms. In addition, a decrease in the CARS score was also observed. The patient tolerated the 3 mg/day aripiprazole treatment well. No side effects were observed, except for moderate levels of sedation. At the end of the 16-week- long treatment, the patient's scale scores were determined as follows: CARS = 31, ABC-irritability = 9, ABC-hyperactivity = 17, CGI-S = 3 (mildly ill), and CGI-I = 2 (much improved).
Discussion
In this article, we presented a 16 week follow-up of aripiprazole treatment in a 23- month-old boy diagnosed with ASD and having symptoms such as intense irritability and hyperactivity. These behavioral issues can result in functional impairment; therefore, behavioral interventions are typically prescribed. Often, patients do not respond to these interventions and require pharmacological treatment (Myers et al. 2007). Aripiprazole is one of the two drugs that have been approved by the United States Food and Drug Administration (FDA) for the treatment of irritability in children and adolescents 6–17 years of age diagnosed with autism (Young and Findling 2015). In the literature, there are studies reporting that aripiprazole is efficient and reliable for the psychopharmacological treatment of irritability, hyperactivity, and stereotypical behavior in children diagnosed with autism. In a naturalistic, open-label study conducted on five subjects 5–18 years old and diagnosed with pervasive developmental disorders (four with autistic disorder, one with Asperger's syndrome), aripiprazole treatment (for at least 8 weeks) was shown to be well tolerated and resulted in significant improvement of CGI-I scores in all cases (Stigler et al. 2004). Findings from another prospective open-label 16-week-long study examining 25 subjects 5–17 years old diagnosed with pervasive developmental disorders (pervasive developmental disorder-not otherwise specified, Asperger's syndrome) were consistent with the previous study (Stigler et al. 2009). Moreover, another study retrospectively evaluated patients between the ages of 5 and 19. Twenty-four out of the 32 patients were diagnosed with autism, and aripiprazole treatment improved the response by 56.0% (Valicenti-McDermott and Demb 2006).
Several reports used large controlled trials and demonstrated aripiprazole to be a therapeutic modality (success rate from 50.0 to 55.0%) for irritability and disorderly behaviors in autistic patients (Marcus et al. 2009; Owen et al. 2009). Similarly, Aman and colleagues executed a line-item examination of the ABC for two placebo-controlled trials of aripiprazole and demonstrated significant improvements in outbursts or tantrums, hyperactivity, and other behaviors such as compulsive hand, body, and head movements (Aman et al. 2010).
Another long-term open-label study (conducted in 2011) evaluated 330 patients and was consistent with the aforementioned randomized controlled study (Marcus et al. 2011). In addition to these studies, there are case reports in the literature that report aripiprazole as an effective treatment of behavioral problems in children with autism (Huang et al. 2010; Kim et al. 2010).
Interestingly, Findling et al. conducted a multicenter, double-blind, randomized, placebo-controlled relapse-prevention trial with subjects 6–17 years of age diagnosed with autism, and reported that there was no significant difference between aripiprazole and placebo (Findling et al. 2014).
In our study, we observed a significant improvement in irritability and hyperactivity symptoms in our patient during aripiprazole treatment. Our findings are consistent with studies in the literature in this subject. It is noteworthy that the existing studies in the literature have generally examined the cases of children >6 years of age (Marcus et al. 2009; Owen et al. 2009; Marcus et al. 2011). The number of studies with 4–5 year-old patients was limited (Stigler et al. 2004; Masi et al. 2009; Stigler et al. 2009) and there were no studies that evaluated aripiprazole treatment in younger patients with autism. This article presents the youngest reported case with ASD whose target symptoms (irritability, hyperactivity) were successfully treated with aripiprazole.
Compared with other typical and atypical antipsychotics, aripiprazole has been associated with fewer side effects (notably, less weight gain, hyperprolactinemia, changes in the QT interval in the electrocardiogram [ECG]) (Stigler et al. 2004; Masi et al. 2009; Stigler et al. 2009; Ho et al. 2012). However, there are some studies that determined extrapyramidal symptom (EPS) rates of aripiprazole being higher than those for risperidone (Marcus et al. 2009). In our study, the patient developed dystonia during the use of risperidone. Except for moderate sedation, the patient did not develop any side effects or EPS during the use of aripiprazole. There were no significant changes in the vital signs or ECG (PR, QRS, RR, QTc).
Conclusions
In conclusion, we report that aripiprazole treatment resulted in significant improvement of irritability and hyperactivity symptoms in a 23-month-old patient with a diagnosis of ASD. Other than moderate sedation, no side effects associated with the drug were detected during the treatment. As far as we know, ours is the youngest reported patient diagnosed with ASD whose behavioral problems improved with aripiprazole treatment. We believe that our study is important in this respect. In addition, early diagnosis and effective regulation of rehabilitation combined with medical treatment (when necessary) are important in this chronic, lifelong disease that affects the quality of life of patients diagnosed with ASD as well as others around them. We believe that our report provides a benefit to treating very young patients diagnosed with ASD when behavioral intervention does not adequately achieve positive results. However, although atypical antipsychotics have been frequently shown to be effective in reducing the severity of symptoms (irritability, hyperactivity, impulsivity, and stereotypical behavior), we know that they carry a risk of several long-term side-effects including weight gain, hyperglycemia, hyperlipidemia, hyperprolactinemia, and movement disorders (Politte and McDougle 2014). Especially, possible problems that pediatric use may cause in the future are not clearly known. Therefore, clinicians should assess the risk–benefit ratio well, before considering the initiation of pharmacological treatment in young children. Considering that ASD is a chronic, lifetime disorder, there is a need for more comprehensive studies on the long-term side-effect profiles of medications.
Footnotes
Disclosures
No competing financial interests exist.