Atomoxetine and Stimulants in Combination for Treatment of Attention Deficit Hyperactivity Disorder: Four Case Reports

Abstract

Atomoxetine and stimulants have both been demonstrated effective as single agents for treatment of attention deficit hyperactivity disorder in children, adolescents, and adults. However, attention deficit hyperactivity disorder symptoms in some patients do not respond adequately to single-agent treatment with these medications, each of which is presumed to impact dopaminergic and noradrenergic networks by alternative mechanisms in different ratios. Four cases are presented to illustrate how atomoxetine and stimulants can be utilized effectively in combination to extend duration of symptom relief without intolerable side effects or to alleviate a wider range of impairing symptoms than either agent alone. This combined pharmacotherapy appears effective for some patients who do not respond adequately to monotherapy, but because there is virtually no research to establish safety and effectiveness of such strategies, careful monitoring is needed.

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

“…The characteristics of patients with ADHD in the three retrospective case reports (Brown 2004;Agarwal and Sitholey 2008;Niederhofer 2009) were similar to those in the prospective studies (e.g., children/adolescents, predominantly male, and predominantly combined ADHD subtype; Table 1). Patients with ADHD in the four remaining retrospective studies (Adler et al 2006;Pohl et al 2009;Scott et al 2010;Hodgkins et al 2011) were children, adolescents, or adults, and were predominantly male (54-82%).…”

“…The three prospective studies were one double-blind, randomized, placebo-controlled, two phase (acute and combination) trial (Carlson et al 2007), and two non-controlled studies: One open, two phase trial reported in two publications Wilens et al 2009); and one switch trial (Quintana et al 2007). The seven retrospective studies were four observational studies: One ongoing (Adler et al 2006) and one complete (Scott et al 2010) chart review, and two claims/ medication database analyses (Pohl et al 2009;Hodgkins et al 2011); and three case reports (Brown 2004;Agarwal and Sitholey 2008;Niederhofer 2009). Findings from the ongoing chart review were published in a conference abstract (Adler et al 2006) and findings from two of the three case reports were published in letters to the editors (Agarwal and Sitholey 2008;Niederhofer 2009).…”

“…Reasons for trying stimulant and atomoxetine combination therapy were reported in the three prospective studies, three of the seven retrospective studies, and the three narrative reviews/ medication algorithms ( Carlson et al 2007;Quintana et al 2007), inadequate response or coverage of symptoms with atomoxetine monotherapy (Brown 2004;Pliszka et al 2006;Lehmkuhl et al 2007;Niederhofer 2009), intolerable side effects with stimulant monotherapy (Brown 2004;Waxmonsky 2005;Lehmkuhl et al 2007;Niederhofer 2009), or tolerance to stimulant monotherapy (Agarwal and Sitholey 2008). In one study Wilens et al 2009), patients received atomoxetine and stimulant combination therapy if they were considered to be partial responders to atomoxetine monotherapy after a 4 week acute atomoxetine treatment phase.…”

“…This drug combination was recommended or implemented to augment stimulant monotherapy (Brown 2004;Waxmonsky 2005;Pliszka et al 2006;Hodgkins et al 2011), to augment atomoxetine monotherapy (Brown 2004;Adler et al 2006;Pliszka et al 2006;Carlson et al 2007;Hammerness et al 2009;Niederhofer 2009;Wilens et al 2009;Hodgkins et al 2011), or during a treatment switch from stimulant to atomoxetine monotherapy (Lehmkuhl et al 2007;Quintana et al 2007;Agarwal and Sitholey 2008). When specified, methylphenidate (particularly OROS methylphenidate) was most often used in combination with atomoxetine (Brown 2004;Carlson et al 2007;Quintana et al 2007;Agarwal and Sitholey 2008;Hammerness et al 2009;Niederhofer 2009;Wilens et al 2009;Hodgkins et al 2011;). The other stimulant used was amphetamine (Brown 2004;Quintana et al 2007).…”

An Open Study of Adjunct OROS-Methylphenidate in Children Who Are Atomoxetine Partial Responders: II. Tolerability and Pharmacokinetics

“…Given the proven efficacy, and variable mechanisms of action of stimulant and nonstimulant (atomoxetine [ATMX]) agents (Wilens 2006), combination treatment with these two classes of agents makes conceptual sense. However, to date, there is a lack of safety and tolerability data for this regimen in children; the literature is limited to case series or clinical reviews of the use of combination ATMX and stimulant therapy in children and adults (Brown 2004;Carlson et al 2007).…”