ATOMOXETINE FOR HOARDING DISORDER: A PRECLINICAL AND CLINICAL INVESTIGATION

Abstract

Purpose of the study Hoarding disorder is a mental disorder that has been newly included in the DSM-5 into the obsessive-compulsive and related disorders chapter. To date only two open studies investigated the pharmacological management of hoarding disorder and its management remains controversial. Despite some studies suggested that childhood attention-deficit hyperactivity disorder (ADHD) and inattention symptoms may be related to hoarding [1], only a small case series study investigated the effectiveness of ADHD medications (metilphenidate) in hoarding disorder [2]. The aim of the present study was to evaluate the preclinical and clinical effectiveness of atomoxetine, a noradrenaline reuptake inhibitor approved for childhood and adulthood ADHD, in an animal model of compulsive-like behaviors (marble burying test) and in two patients with a primary diagnosis of hoarding disorder. Methods We performed a preclinical investigation assessing the effects of atomoxetine on the marble burying behavior test in mice. During the test, mice were placed individually in a clear plastic box containing 24 black marbles (1 cm diameter), evenly spaced on 5 cm sawdust. The number of marbles buried (to at least 60% of the depth of the sawdust) within 30 min in vehicle and atomoxetine treated groups was measured. Atomoxetine (10, 30 and 60 mg kg-1) was administered per os 30 min before the test. Subsequently, we conducted a clinical investigation on two patients fulfilling the DSM-5 criteria for hoarding disorder. These patients were treated with atomoxetine 40-100 mg for 12 weeks. A history of adult or childhood ADHD was excluded through the diagnostic interview DIVA 2.0. No changes of the ongoing medications or psychotherapy were allowed during the treatment period. To measure the severity of hoarding, the Saving Inventory-Revised (SI-R) and the UCLA Hoarding Severity Scale (UHSS) were administered before and after the treatment. Response was defined as a more of 30% decrease in UHSS and SI-R scores and at least “much improved” on the Clinical Global Impression/Improvement (CGI-I) scale. Results Atomoxetine significantly reduced the number of buried marbles in a dose dependent manner in comparison to control mice, without affecting the locomotor activity. Atomoxetine (30 and 60 mg kg-1) significantly reduced the number of buried marbles in a dose dependent manner (12.3 ± 1.0 and 10.0 ± 1.8, respectively) in comparison to control mice (19.3 ± 1.0), without affecting the locomotor activity. Atomoxetine 10 mg kg-1 was not effective (21.3 ± 0.9). Atomoxetine-treated patients were both classified as treatment responders after 12 weeks of treatment. Atomoxetine was well tolerated during all the treatment period. Furthermore, both patients as were still classified responders at the 6 months follow-up visits. Conclusions These preclinical and clinical data suggest that atomoxetine may be considered as a potentially effective compound for hoarding disorder. Therefore, atomoxetine should be considered for future controlled trials in hoarding disorder.