Atomoxetine Induced Obsessive-Compulsive Disorder

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Introduction
Attention deficit and hyperactivity disorder (ADHD), a common neurodevelopmental disorder, is being diagnosed with gradually increasing frequency.It is reported at the rate of 5% in children.The clinical picture of ADHD manifests itself with inattention and hyperactivityimpulsivity that disturb the functionality or development of an individual. 1 Since the symptoms affect social and academic achievement and physical condition, treatment is often required; pharmacological agents, both stimulants and nonstimulants, are frequently used in its treatment. 2tomoxetine is a selective, presynaptic, norepinephrine reuptake inhibitor also known as a NET inhibitor.It was the first non-stimulant medication to receive FDA approval for the treatment of ADHD. 3 In this article, a case in which atomoxetine was initiated due to ADHD and OCD developed during the treatment is reported.

Case Presentation
An 11-year-old male patient was brought to our polyclinic by his family with complaints of school failure, hyperactivity, and attention deficit.As a result of a psychiatric evaluation, he was diagnosed with "ADHD, mixed type".The patient's family history revealed that his mother had an anxiety disorder, his aunt had a diagnosis of obsessive-compulsive disorder (OCD), and both had received drug treatment.The patient had a height of 140 cm, body weight of 25 kg, and blood pressure of 100/65 mm Hg.His routine laboratory and cardiac evaluations were found to be normal.Long-acting methylphenidate at a dose of 18 mg/d was initiated for the patient but discontinued because the patient had intense agitation, anorexia, retreating, and paranoid thoughts after methylphenidate treatment.Treatment with 10 mg/day atomoxetine was initiated one month later, after the disappearance of these symptoms.An atomoxetine dose of 18 mg/d was initiated upon the absence of any side effect and the partial reduction of symptoms in the first-month control.In the control performed 1 month later, the patient complained of being unable to be sure, having obsessive thoughts of being seriously ill and dying, needing constant suggestions, asking repeated questions, and receiving only temporary relief when answers were given that started 3 days after the dose of atomoxetine was increased.The patient's mother indicated that these complaints intensified especially in the evening hours and lasted for many hours.Based on DSM-5 criteria, the patient was diagnosed with OCD attributed to atomoxetine, and the drug treatment was discontinued.
The treatment of 10 mg atomoxetine was again initiated for the patient whose OCD symptoms improved markedly 1 week after drug discontinuation.One month later, during the control of the patient, the partial regression of ADHD symptoms and no OCD symptoms were observed.

Discussion
ADHD is a neurodevelopmental disorder frequently seen in children and adolescents.Previous studies have reported that it coexists with many psychiatric diseases and that this coexistence may be due to common structural and functional disorders. 4,5One of the most common disorders coexisting with ADHD is special learning disorder. 6These two disorders have been reported to originate from the same specific gene. 5Furthermore, ADHD, OCD, autism, and schizophrenia are also described as neurodevelopmental frontostriatal disorders due to the presence of common functional and structural abnormalities in cortico-striatal ami-cortical structures. 7he amount of evidence regarding the coexistence of ADHD and sleep disorder has recently been increasing. 4herefore, ADHD should not be considered as a single disease but as a complex disorder associated with other potential psychiatric disorders.Atomoxetine, a nonstimulant drug used in the treatment of ADHD, is the selective blocker of presynaptic norepinephrine carriers in the central nervous system. 3[10] The use of atomoxetine is known to cause side effects such as headache, sleep disorders, increases in blood pressure, cardiac problems, suicidal tendencies, and restlessness. 8,11owever, in the literature, only 1 case report has indicated that atomoxetine causes OCD.In that case, OCD symptoms did not occur at 25 mg/d and 40 mg/d doses of atomoxetine; it was observed only when the dose was increased to 60 mg/d.OCD symptoms continued although a 40 mg/d dose of atomoxetine was initiated for the patient, and it was reported that OCD symptoms disappeared with the discontinuation of atomoxetine. 12OCD symptoms were also observed in the current case as a result of dose increase similar to the previously reported case; however, unlike the previously reported case, OCD was observed at a very low dose (18 mg/d), and the symptoms were not repeated with dose reduction.
In OCD patients, an increased dopaminergic function was detected in the brain. 13Atomoxetine is a noradrenaline reuptake (NET) inhibitor.It also increases extracellular levels of dopamine in the prefrontal cortex, believed to result from NET inhibition. 14Studies have reported the coexistence of OCD and ADHD to be common. 15In the present case, a child with ADHD who may be predisposed to OCD, atomoxetine, which is the NET inhibitor, may have triggered OCD symptoms by increasing dopaminergic activity in the prefrontal cortex.

Conclusion
The case reported herein is the second one caused by the use of atomoxetine.When these two cases are evaluated, OCD development due to atomoxetine may occur at different doses, and when OCD develops, dose reduction may be the solution, or the discontinuation of atomoxetine may be necessary.Clinicians should be careful when considering an atomoxetine-OCD association.