The purpose of this study was to conduct a systematic review of the pharmacological options available to treat patients diagnosed with attention-deficit hyperactivity disorder and anxiety disorder, for generating evidence on the safest, most-effective and tolerable pharmacotherapy. To this end, a systematic search was performed in three electronic databases (Medline, Scopus and Directory of Open Access Journals; December 2017). Randomized, double-blind, parallel-design clinical trials evaluating the efficacy, safety or tolerability of therapies for attention-deficit hyperactivity disorder and anxiety disorder in children and adolescents or adults were considered. A total of 1960 articles were retrieved from the databases, of which five studies were included in the qualitative synthesis. Two of these studies evaluated the drug atomoxetine, another study evaluated desipramine, and the remaining two studies evaluated methylphenidate, with fluvoxamine being associated with methylphenidate in one of the trials. Owing to the high heterogeneity among studies, it was not possible to combine data for meta-analyses. Although only few studies have been evaluated in this systematic review, the results point to a more significant benefit of atomoxetine. This is probably because this drug was studied in a wider age range and evaluated by more specific scales for both disorders. To further strengthen this evidence, randomized, controlled and multicenter clinical trials with larger sample sizes should be conducted.

Attention-deficit/hyperactivity disorder (ADHD) is a clinical syndrome characterized by persistent inattention, impulsivity and hyperactivity. It is most commonly encountered in children and adolescents, but may persist into adulthood. A variety of psychostimulant and non-psychostimulant medications have proven to be successful in reducing inattention, impulsivity and hyperactivity in those with ADHD. Psychostimulants used to treat ADHD include methylphenidate and related drugs and various amphetamine preparations. Non-psychostimulant medications used to treat ADHD include atomoxetine and two alpha-2 adrenergic agonists; guanfacine extended-release and clonidine extended-release. The psychostimulants and atomoxetine have been shown, on average, to increase heart rate by 3-10 beats/min, systolic blood pressure by 3-8 mmHg, and diastolic blood pressure by 2-14 mmHg. These drugs may also delay ventricular repolarization. The alpha-2 adrenergic agonists may reduce heart rate and blood pressure. For these reasons, there is concern about the safety of psychostimulant and non-psychostimulant medications in patients with ADHD. In Part 1 of this 2 part review we discuss the epidemiology and natural history of ADHD, describe the pharmacology of drugs used to treat ADHD, and discuss in detail studies assessing the effects of ADHD drugs on blood pressure, heart or pulse rate and electrocardiographic indices of ventricular repolarization.

The human brain is able to flexibly adapt its information processing capacity to meet a variety of cognitive challenges. Recent evidence suggests that this flexibility is reflected in the dynamic reorganization of the functional connectome. The ascending catecholaminergic arousal systems of the brain are a plausible candidate mechanism for driving alterations in network architecture, enabling efficient deployment of cognitive resources when the environment demands them. We tested this hypothesis by analyzing both resting-state and task-based fMRI data following the administration of atomoxetine, a noradrenaline reuptake inhibitor, compared with placebo, in two separate human fMRI studies. Our results demonstrate that the manipulation of central catecholamine levels leads to a reorganization of the functional connectome in a manner that is sensitive to ongoing cognitive demands.

Attention Deficit Hyperactivity Disorder (ADHD) causes impaired visuospatial working memory (VWM), which primarily maps to the prefrontal cortex. However, little is known about the synaptic processes underlying cognitive loss in ADHD, or those ultimately involved in the preventive effect observed through the clinical use of Atomoxetine (ATX). To investigate the plasticity underlying ADHD related cognitive loss, and that potentially involved in the preventive action of Atomoxetine, allocentric VWM was assessed, as well as the dendritic spine number and proportional density on pyramidal neurons in the prefrontal cerebral cortex layer III of neonatal 6-hydroxydopamine-lesioned rats. The effect of acute ATX treatment was also assessed at 28 days of age. 6-OHDA induced lesions produced increased motor activity and a loss of VWM, concomitant with a reduction in thin spine density. ATX administration reversed cognitive loss, in conjunction with a decrease in thin spines and an increase in mushroom spines. A reduction in the proportion of spines involved in learning in hyperactive animals could account for the loss in cognitive function observed. Considering thin spine density was also reduced after ATX administration, we hypothesized that the restoration in cognitive function recorded could be brought about by an increase in memory related mushroom spines.

The case describes an adult diagnosed with attention deficit hyperactivity disorder and treated with atomoxetine who quickly developed a florid case of delusional infestation. The patient described very distressing experiences that were significantly impacting her daily life. The symptoms improved with the withdrawal of atomoxetine and resolved completely with antipsychotic medications. Atomoxetine is proposed as the putative causative agent in this case.