A Systematic Review of Combination Therapy with Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder, Including Patient Characteristics, Treatment Strategies, Effectiveness, and Tolerability

Abstract

Objective: The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. Methods: Literature databases (MEDLINE Ò , EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. Results: Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. Conclusions: Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success.

Canadian Guidelines on Pharmacotherapy for Disruptive and Aggressive Behaviour in Children and Adolescents with Attention-Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, or Conduct Disorder

“…Despite widespread use of atomoxetine in combination with a psychostimulant, evidence to support this practice is very limited. 28 Adverse effects of atomoxetine are generally minor, but it may be associated with a small increase in risk (0.4% to 0.5%) of suicidal ideation or behaviour. [29][30][31] Guanfacine (Monotherapy or in Combination With a Psychostimulant) for Oppositional Behaviour in Children and Adolescents With ADHD, With or Without ODD…”

Brief report of efficacy and side effect profile of crossing over to modified-release capsules of methylphenidate in ADHD patients receiving other treatments: case series

“…Proven effective psychopharmacological treatments are mainly divided into two groups: stimulants and non-stimulants [4]. Possible pharmacologic mechanisms of stimulants are (1) increasing extracellular levels of dopamine via blocking dopamine transporters and (2) potentiation of dopamine neurotransmission via enhancing the binding of dopamine in the prefrontal cortex of the brain [5].…”

“…Clonidine and guanfacine are not used widely in the treatment of ADHD in Turkey while ATX is prescribed frequently. ATX is a selective noradrenaline reuptake inhibitor, acting by increasing the amount of noradrenaline in synaptic gaps via inhibition of noradrenaline transporter in the prefrontal cortex [4].…”

Combined methylphenidate and atomoxetine pharmacotherapy in attention deficit hyperactivity disorder

“…Comorbid disorders like oppositional defi ant disorder, anxiety disorders, learning disorders are frequent in children with ADHD (Cheng et al 2007). In a recent metaanalysis worldwide ADHD prevalence in children and adolescents was found to be 5,29% (Treuer et al 2013).…”

“…ADHD treatment success rates with pharmacotherapy are 80 -90%, while 10 -20% of patients are treatment resistant (Treuer et al 2013). Pharmacological agents are mainly divided into two subgroups: stimulants and non-stimulants (Treuer et al 2013).…”