Effects of Commonly Used ADHD Medications on Comorbid Anxiety
Stimulants are first-line treatment for ADHD and reduce both hyperactivity and inattentive symptoms.7 Expectations regarding the effect of stimulants treatment on both ADHD and anxiety depends in part on whether anxiety is an independent condition or secondary to ADHD impairment. Most short-term studies do not make this differentiation and should be interpreted with caution. In the 1990s, short-term studies indicated that stimulants administered to children with comorbid ADHD and anxiety led to more side effects and a poorer response to psychostimulants.16 Later, longer-term stimulant studies17 show that improvements in ADHD were comparable for children exhibiting ADHD with and without comorbid anxiety. Children administered psychostimulants also showed some improvement in anxiety.16 When ADHD-related anxiety impairment continues, additional pharmacotherapy targeting anxiety specifically may be indicated.
Atomoxetine is a norepinephrine reuptake inhibitor that is US Food and Drug Administration-approved for the treatment of ADHD in children age 8 to 17 years.18 Atomoxetine, which has moderate anti-anxiety effects,19 may be used as monotherapy for ADHD or in combination with a stimulant.7 An open comparison study showed that after 8 weeks, atomoxetine is as effective as methylphenidate for ADHD with additional improvement on anxiety symptoms as compared to methylphenidate.20 The challenge with interpreting this study (and any study targeting co-occurring conditions) is determining whether atomoxetine reduced ADHD and secondary anxiety, reduced anxiety and secondary attentional issues, or treated both. As atomoxetine has not been studied in children with anxiety disorders only, it cannot be claimed that atomoxetine treats anxiety. Advantages of atomoxetine for ADHD include: (1) it is not a controlled substance; (2) minimal appetite suppression, and (3) 24-hour efficacy. The main disadvantages include (1) needing to wait 3 to 6 weeks for treatment response and (2) lower effect size for treating ADHD7 and/or anxiety symptoms compared to stimulants or selective serotonin reuptake inhibitors (SSRIs).
The alpha agonists, clonidine and guanfacine in extended-release forms, are used to treat ADHD as monotherapy with moderate effect size or adjunctively with stimulants.7 Guanfacine extended-release was well tolerated in children and adolescents with anxiety disorders, but was not statistically better compared to placebo.21 Advantages of alpha agonists include (1) not being controlled substances, (2) minimal appetite suppression, and (3) 24-hour efficacy. Sedation, a common side effect, is mitigated to some extent by extended-release forms. The main disadvantage is needing to wait a few weeks to note treatment response and needing to taper when discontinuing treatment to avoid rebound hypertension.
Effects of Medications Used for Anxiety on Comorbid ADHD
SSRIs are first-line pharmacotherapy for anxiety disorders in children and adolescents. SSRIs have no known positive or negative effects on the core symptoms of ADHD.
Drug-drug interactions between ADHD medications and SSRIs. There are no major drug-drug interactions between stimulants and SSRIs or alpha agonists and SSRIs. Fluoxetine and atomoxetine are both metabolized by cytochrome P450 2D6, and when taken together can increase each other's serum levels. Other drugs that mutually increase serum level with atomoxetine include paroxetine, bupropion, quinidine, and cimetidine.
Effects of treating anxiety on ADHD symptoms. To the extent that anxiety interferes with attention and executive functioning,11 treating anxiety may improve overall capacity to focus and executive functioning. For children with ADHD whose impulsivity is tempered by their anxiety disorder, treating anxiety may result in more impulsive behavior.
Nonpharmacologic treatment strategies for children with comorbid ADHD and anxiety. Children with ADHD and anxiety benefit from structured home environments with regular schedules, clear expectations, routines, rules, and consequences, and calm, neutral approaches to discipline.
For younger children with ADHD or anxiety, parent education about the disorders and how to support their child's unique needs is essential. Formal parent management training may benefit parents of children with ADHD and disruptive behavior. For children with anxiety disorders, first-line psychotherapy is cognitive-behavioral therapy (CBT) with graded exposures in which the child learns to master the experience causing anxiety, gradually extinguishing the fear response.
Determining an initial treatment approach. It may not always be apparent that a child has both ADHD and an anxiety disorder. If anxiety disorder is present (eg, separation, generalized, or social anxiety disorders) these symptoms may dominate and anxiety symptoms may need to be well controlled before attention problems become apparent. Children who are chronically restless, inattentive, and with limited capacity to describe their emotions may not be identified with an anxiety disorder until treated for ADHD. Failure to respond to treatment as expected should prompt a reassessment of the diagnosis, and comorbid ADHD or anxiety should be in the differential diagnosis for each other on reassessment.
Which disorder has more impact on the child's functioning? Current practice parameters7 and practice guidelines22 indicate initiating pharmacologic treatment depending on which disorder most impairs the child's functioning. When both disorders are present, current practice parameters7 recommend assuming the two disorders are indeed present and developing treatment plans for both. If it is unclear whether comorbidity is present or which disorder is more impairing, the most conservative approach to treatment involves initiating a psychostimulant and carefully monitoring treatment progress. This approach addresses the ADHD symptoms and may also reduce symptoms that are potentially anxiety related. If anxiety symptoms are consistent with one of the anxiety syndromes and are impairing, specific treatment for anxiety is warranted.
Which can we treat faster? It is possible to get pharmacotherapy for ADHD and anxiety underway quickly. When starting ADHD treatment with a stimulant, treatment response can be established in a few days to a few weeks. Stimulants start working immediately, and doses can be adjusted every few days. Stimulant side effects can emerge quickly, allowing patients and families to readily make decisions about acceptability. Nonstimulant medications for ADHD (atomoxetine and the alpha-agonists) require slow upward adjustments to avoid side effects, and up to 3 weeks at the target dose to see the full therapeutic effect at that dose. SSRIs for anxiety also require 3 to 6 weeks to assess for therapeutic efficacy. Starting ADHD treatment with a stimulant, followed by an SSRI for anxiety, is the most time-efficient strategy for pharmacotherapy for both disorders.
If we only want to use one medication, which one? Sometimes, the clinician wishes to keep pharmacotherapy of comorbid ADHD and anxiety to a minimum. Parents or patients may be uncomfortable with psychotropic medications in general, wish to avoid a particular class of medications, or only want to take one medication per day. Children with ADHD and anxiety may also have medical comorbidities and other potential drug-drug interactions. In these cases, one might consider a stimulant for the most effective treatment of the ADHD, combined with CBT for the anxiety. Despite caveats noted above, atomoxetine may address symptoms of both ADHD and anxiety.