Abstract
A
An 11-year-old nonverbal boy, who had a previous diagnosis of ASD based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, was admitted to our outpatient service with complaints of refusing to eat and drink, irritability, aggression, self-mutilation, and sleep disturbance. His mother reported that, because of the RRBs related to the feeding procedures, he had been refusing to eat or drink during the previous 12 days. He was also reported to have difficulty sleeping because of his RRBs. His mother reported that he had been making various hand, head, and trunk movements. These included touching his hands to his head and to the plate of food, and ultimately performing these together with various meaningless voices and swinging. He had been eating after making these ritualistic behaviors for 5–6 years before the admission. However, because these behaviors had increased over the previous 3 months, the child began to eat over longer time periods. After these behaviors worsened, the child refused to eat beginning 12 days before his admission. His mother described the eating ritual as: “He sits at the table to eat and begins making his ritual movements. After making these movements for about 30 minutes, and because he could not begin eating, he gets angry and gets up from the table.” His sleep had worsened within 3 months of the period in which the RRBs had intensified. He had been making similar repetitive movements before going to sleep, and his mother described his recent difficulty in falling asleep as being due to an increase in repetitive behaviors.
In the psychiatric evaluation, the child was nonverbal and showed serious RRBs and social deficits, including an absence of eye contact and a reluctance to attend to social interactions. The RRBs observed during the psychiatric evaluation included touching his ear with his hands and hurting himself (slapping). He was also irritable, aggressive, and made meaningless and disturbing noises during the examination. Aripiprazole (5 mg/day) and mirtazapine (15 mg/day) were started to target his RRBs, self-mutilative and aggressive behaviors, and sleep and food intake problems. Because the patient needed an urgent intervention that would protect the child from possible detrimental effects of starvation, we decided to give two medications together to provide an effective treatment. After starting the medication, the patient's aggression, irritability, sleep problems, and RRBs decreased gradually and he began to eat and drink during the first week of treatment. His family reported no problems related to eating and sleep 4 weeks after starting the medications. Although the RRBs did not disappear, the child could eat, drink, and sleep after making RRBs for shorter periods of time. He had no problems related to eating, sleeping, or behavioral issues during the 7 months of follow-up. At the seventh month of treatment, the plan was to lower the doses of the two drugs and discontinue them consecutively. Thus, we planned to terminate mirtazapine first because of its disturbing side effects, which included sedation. However, when the dose was lowered to 7.5 mg/day, the self-injurious behaviors and irritability began again within a week. The dose was then increased to 15 mg/day and the symptoms disappeared again.
Here, we report the case of a nonverbal boy with ASD whose eating and sleeping problems were reduced after aripiprazole and mirtazapine treatments, which were used to reduce his severe RRBs. Treatment of RRBs in children with ASD, which may impair their lives (Gabriels et al. 2005; Harrop 2015), is a complicated issue and no specific treatment method has been suggested on this issue. Various types of antipsychotics (e.g., haloperidol, risperidone, and aripiprazole), serotonin reuptake inhibitors (e.g., fluoxetine and clomipramine), and divalproex have been reported to improve the RRBs in children with ASD (McDougle et al. 2000; Hollander et al. 2004, 2006; Soorya et al. 2008). Aripiprazole is an atypical antipsychotic drug that has a partial agonistic activity on D2 and 5-HT1A receptors, and an antagonistic activity on 5-HT2A receptors. It was approved for the treatment of irritability in children and adolescents with ASD by the Food and Drug Administration (FDA) after two placebo-controlled studies (Marcus et al. 2009; Owen et al. 2009). In addition, it has been reported that aripiprazole is useful in reducing RRBs and irritability in a variety of open-label studies in children with ASD (Stigler et al. 2009). RRBs have been described as compulsive features that have similarities with obsessive compulsive disorder (OCD) (Zandt et al. 2009). Aripiprazole has been proposed for adjunctive treatment with selective serotonin reuptake inhibitors (Masi et al. 2010), or for single-use treatments in OCD patients (Sertdemir and Akça 2017). Mirtazapine is an antidepressant that has been shown to have antagonistic activities on serotonergic (i.e., 5-HT3), histaminergic (i.e., H1), and alpha adrenergic (i.e., α2) receptors (Stimmel et al. 1997). It has various side effects including an increase in appetite, weight gain, and sedation (Stimmel et al. 1997). In our case, mirtazapine treatment may have been helpful for the sleep and appetite problems. In addition, an open-label trial and two case reports have described the efficacy of mirtazapine in hypersexual and self-injurious behaviors, irritability, and aggression (Nguyen and Murphy 2001; Posey et al. 2001; Coskun et al. 2009). In our present case, after the treatment of mirtazapine was stopped, the self-injurious behaviors began again. However, when we started mirtazapine treatment a few days later, these behaviors disappeared again. This suggests that mirtazapine can be helpful in treating the aggression and irritability symptoms of children with ASD. In this case report, we presented a child with ASD whose eating and sleeping problems, which were related to RRBs, improved with aripiprazole and mirtazapine treatments. Further studies are needed to improve our knowledge on this topic.
Footnotes
Disclosures
The authors do not have any actual or potential conflict of interest including any financial, personal, or other relationship with other people or organizations that could inappropriately influence or be perceived to influence.