Atomoxetine-induced mania with auditory hallucination in an 8-year-old boy with attention-deficit/hyperactivity disorder and tic disorder.

Abstract

[Author Affiliation]Chia-Chien Liu. 1 Department of Psychiatry, National Yang-Ming University Hospital, Yilan, Taiwan, Republic of China.Chen-Chia Lan. 2 Department of Psychiatry, Taipei Municipal Gan-Dau Hopsital, Taipei, Taiwan, Republic of China.Ying-Sheue Chen. 3 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.Address correspondence to: Ying-Sheue Chen, MD, Department of Psychiatry, Taipei Veterans General Hospital, Taiwan, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, ROC, E-mail: moominess@gmail.comTo The Editor:The prevalence rate of attention-deficit/hyperactivity disorder (ADHD) is ∼5.9-7.1% among children and adolescents (Willcutt 2012). Tic disorder is a common comorbid disorder in patients with ADHD (Gau et al. 2010). Central nervous system (CNS) stimulants such as methylphenidate are the first line treatment for ADHD, but have the potential to worsen tics in individual patients with comorbid tic disorder (Pringsheim and Steeves 2011). Atomoxetine is considered a reasonable alternative, in that it may not exacerbate tics, while improving ADHD symptoms (Bloch et al. 2009). Atomoxetine-induced psychiatric adverse effects have been reported in adult (Steinberg and Chouinard 1985) and adolescent patients (Henderson 2004; Tang, et al. 2009; Bahali et al. 2013; Guney and Uneri 2014). We hereby report an 8-year-old boy with ADHD and comorbid tic disorder, who developed mania and auditory hallucinations (AH) after increased doses of atomoxetine. Important clinical differences with previous cases, possible mechanisms, risk factors, and practical management issues are also discussed.Case ReportAn 8-year-old boy had been diagnosed at 6 years of age with ADHD, combined type, and chronic motor tic disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria (American Psychiatric Association 2000). His older sister had ADHD with comorbid Tourette's disorder. The patient had received atomoxetine 25 mg/day (1.1 mg/kg/day) for ADHD, and aripiprazole 10 mg/day for tic disorder, with obvious clinical improvement. At age 7, atomoxetine was increased to 40 mg/day (1.7 mg/kg/day) because the patient was inattentive and impatient doing homework, in addition to exhibiting hyperactive symptoms such as hopping around and fidgeting in class. After 3 weeks of increasing doses, the patient developed AH: A male voice calling his name. He responded to it frequently by turning his body, walking toward the voice, gesturing, and talking back. Elevated and irritable mood, decreased need of sleep, excessive talking, racing thoughts, and frequent arguments with classmates were also noted. Atomoxetine was decreased to 25 mg/day, with aripiprazole maintained at 10 mg/day, and the manic symptoms, and AH gradually subsided within 2 weeks.At age 8, atomoxetine was increased to 25 mg/40 mg every other day for ADHD symptoms of inattention, fooling around, and completing assignments slowly at school and at home. After the dosage adjustment, ADHD symptoms improved without obvious side effects. Six months later, the patient's parents accidentally increased the dose to 40 mg every day, and once again, manic-like symptoms including being hypertalkative, and having increased thought content and a decreased need of sleep developed within 2 weeks. However, no AH were noted this time. Atomoxetine was shifted back to 25 mg/40mg every other day and the abovementioned symptoms resolved within 1 week.Because of the development and resolution of psychotic symptoms closely followed the increasing and decreasing of atomoxetine dosage, atomoxetine-induced mania and AH were highly suspected.DiscussionThis 8-year-old boy is the youngest case of atomoxetine-induced mania and AH ever reported. Atomoxetine is a norepinephrine reuptake inhibitor and exerts its therapeutic effect by increasing norepinephrine concentration in the brain (Christman et al. …