Treatment of Anxiety in Patients Already on Atomoxetine
For patients with ADHD on atomoxetine who develop anxiety, add an SSRI (fluoxetine or sertraline) to the existing atomoxetine regimen, as this combination has been specifically studied and shown to be safe and effective. 1, 2, 3
Primary Recommendation: Add SSRI to Atomoxetine
SSRIs (fluoxetine and sertraline) are the treatment of choice for anxiety in patients with ADHD, including those already on atomoxetine, based on their evidence for efficacy and established safety profile. 1
The combination of atomoxetine and fluoxetine has been specifically studied in pediatric patients with ADHD and comorbid anxiety/depressive symptoms, demonstrating that this combination is well tolerated with marked reductions in both ADHD and anxiety symptoms. 3
In a randomized trial of 173 patients (ages 8-17), combined atomoxetine/fluoxetine therapy showed significant improvements in anxiety symptoms (p < .001) with similar completion rates and discontinuation rates for adverse events as atomoxetine monotherapy. 3
FDA labeling confirms that atomoxetine does not worsen anxiety in patients with comorbid anxiety disorders, as demonstrated in two double-blind, placebo-controlled trials involving both pediatric and adult populations. 2
Dosing and Monitoring Considerations
When adding an SSRI to atomoxetine, monitor blood pressure and pulse more closely, as the combination group showed greater increases in these parameters compared to monotherapy. 3
Be aware of CYP2D6 interactions: SSRIs like fluoxetine and paroxetine inhibit CYP2D6, which can elevate atomoxetine levels and require dose adjustment. 4, 5
Continue atomoxetine at current dose while initiating SSRI at standard starting doses (fluoxetine 10-20 mg daily or sertraline 25-50 mg daily). 1
Alternative Options (Second-Line)
Alpha-2 agonists (clonidine or guanfacine) can be used for anxiety management in patients with ADHD, though there are no trials specifically investigating their use for anxiety in this population. 1
Guanfacine (1-4 mg daily) is particularly useful when anxiety or agitation is present due to its calming effects, with 2-4 weeks required for full effect. 5
Avoid benzodiazepines in patients with ADHD, as they are not recommended for chronic anxiety treatment due to concerns about behavioral side effects such as disinhibition. 1, 5
Clinical Evidence Supporting Combination Therapy
An open-label study of 29 adults with ADHD and comorbid partially responsive generalized anxiety showed that adjunctive atomoxetine to SSRIs/SNRIs resulted in significant resolution of anxiety symptoms (HAM-A scores, p<.001 at 12 weeks) with 93% study completion. 6
Atomoxetine monotherapy alone can improve anxiety symptoms in patients with ADHD and comorbid anxiety, though the addition of an SSRI provides more targeted anxiety treatment. 7, 3, 8
In FDA trials, 442 adults with ADHD and social anxiety disorder treated with atomoxetine (mean dose 83 mg/day) showed no worsening of anxiety as measured by the Liebowitz Social Anxiety Scale. 2
Important Safety Considerations
Monitor for suicidal ideation closely, particularly when combining atomoxetine with SSRIs, as both carry FDA warnings about increased suicidal thoughts in children and adolescents. 4, 5
The combination is generally well tolerated with no significant cardiovascular concerns beyond routine monitoring of blood pressure and heart rate. 6, 3
Common side effects of the combination include decreased appetite, nausea, and initial somnolence, but these are typically mild and transient. 4, 3
Common Pitfalls to Avoid
Do not discontinue atomoxetine to switch to an SSRI alone, as SSRIs are not effective for ADHD symptoms and the patient would lose ADHD symptom control. 5
Do not assume atomoxetine alone will adequately treat both ADHD and anxiety in all patients; while it may help both conditions, adding an SSRI provides more robust anxiety treatment. 1, 3
Avoid bupropion as an alternative, as it is inherently activating and can exacerbate anxiety or agitation in patients who already have anxiety symptoms. 5