How to manage anxiety in patients taking Strattera (atomoxetine)?

Managing Anxiety in Patients Taking Strattera (Atomoxetine)

Atomoxetine does not worsen anxiety in patients with ADHD and comorbid anxiety disorders, and can be safely continued while addressing anxiety symptoms through evidence-based interventions. 1

Evidence Supporting Atomoxetine Safety in Anxiety

The FDA label for atomoxetine provides definitive evidence from two well-designed postmarketing trials demonstrating that atomoxetine does not worsen anxiety in patients with ADHD and comorbid anxiety disorders:

• In pediatric patients (ages 8-17): A 12-week double-blind, placebo-controlled trial of 176 patients with ADHD and comorbid separation anxiety disorder, generalized anxiety disorder, or social phobia showed atomoxetine (median dose 1.30 mg/kg/day) did not worsen anxiety as measured by the Pediatric Anxiety Rating Scale (PARS). 1

• In adult patients (ages 18-65): A 16-week trial of 442 patients with ADHD and social anxiety disorder (23% also had generalized anxiety disorder) showed atomoxetine (mean dose 83 mg/day) did not worsen anxiety as measured by the Liebowitz Social Anxiety Scale (LSAS). 1

• Atomoxetine is particularly useful for patients with comorbid anxiety or tics, as it does not exacerbate these conditions. 2, 3

Treatment Algorithm for Anxiety Management

Step 1: Continue Atomoxetine and Assess Anxiety Severity

• Do not discontinue atomoxetine based on anxiety concerns, as evidence demonstrates it does not worsen anxiety symptoms. 1
• Explore the patient's specific concerns and anxieties to identify reversible psychological factors. 4
• Ensure effective communication about the safety profile of atomoxetine in anxiety disorders. 4

Step 2: Initiate First-Line Pharmacological Treatment for Anxiety

For children and adolescents (ages 6-18):

• Start an SSRI as first-line treatment: Sertraline (starting 25-50 mg daily) or escitalopram (starting 5-10 mg daily) are preferred due to established efficacy and favorable safety profiles. 4, 5
• Begin with a subtherapeutic "test" dose to minimize initial anxiety or agitation that can occur with SSRIs. 4
• Titrate sertraline by 25-50 mg increments every 1-2 weeks as tolerated (target 50-200 mg/day). 5
• Titrate escitalopram by 5-10 mg increments every 1-2 weeks (target 10-20 mg/day). 5
• Expected response timeline: Statistically significant improvement by week 2, clinically significant improvement by week 6, maximal benefit by week 12 or later. 4, 5

For adults:

• Start an SSRI: Escitalopram or sertraline are top-tier first-line agents. 5
• Alternative SNRI option: Venlafaxine extended-release 75-225 mg/day or duloxetine 60-120 mg/day if SSRIs are ineffective or not tolerated. 4, 5

Step 3: Add Cognitive Behavioral Therapy (CBT)

• Combination treatment (CBT + SSRI) is superior to either treatment alone for social anxiety, generalized anxiety, separation anxiety, and panic disorder. 4
• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness. 5
• CBT should include: education on anxiety, cognitive restructuring, relaxation techniques, and gradual exposure when appropriate. 5
• Recommend 12-20 structured CBT sessions for significant symptomatic improvement. 5

Step 4: Manage Acute Anxiety Episodes

For acute anxiety requiring immediate intervention:

• Lorazepam 0.5-1 mg orally up to four times daily as needed (maximum 4 mg in 24 hours) is the NICE guideline-recommended first-line treatment. 4, 6
• Reduce dose to 0.25-0.5 mg in elderly or debilitated patients (maximum 2 mg in 24 hours). 4
• Oral tablets can be used sublingually for faster onset. 4

Step 5: If First SSRI Fails After 8-12 Weeks

• Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) after 8-12 weeks at therapeutic doses with inadequate response. 5
• Consider switching to an SNRI (venlafaxine or duloxetine) if second SSRI trial is ineffective. 4, 5
• Monitor venlafaxine for blood pressure increases. 5

Critical Monitoring and Safety Considerations

SSRI/SNRI Monitoring

• Monitor for suicidal thinking and behavior, especially in the first months of treatment and following dose adjustments (pooled risk difference 0.7% vs placebo, NNH = 143). 4
• Common side effects include nausea, headache, insomnia, dry mouth, diarrhea, somnolence, and sexual dysfunction; most emerge within the first few weeks and are generally mild and transient. 4, 5
• Monitor for behavioral activation/agitation (motor restlessness, insomnia, impulsiveness, disinhibited behavior), which is more common in younger children and typically occurs early in treatment or with dose increases. 4
• Assess response using standardized anxiety rating scales (e.g., HAM-A, PARS). 4, 5

Atomoxetine-Specific Considerations

• Atomoxetine is metabolized by CYP2D6; poor metabolizers have 10-fold higher plasma concentrations but similar adverse event profiles to extensive metabolizers. 7
• Concomitant use of potent CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) reduces atomoxetine clearance in extensive metabolizers. 2, 7
• Atomoxetine has minimal drug-drug interactions compared to SSRIs and does not inhibit or induce CYP enzymes. 7

Common Pitfalls to Avoid

• Do not discontinue atomoxetine due to anxiety concerns without recognizing that FDA-approved labeling demonstrates it does not worsen anxiety. 1
• Avoid paroxetine as first-line SSRI due to higher risk of discontinuation syndrome and potentially increased suicidal thinking compared to other SSRIs. 4, 5
• Do not escalate SSRI doses too quickly; allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window. 4, 5
• Do not abandon treatment prematurely; full SSRI response may take 12+ weeks. 5
• Taper SSRIs gradually when discontinuing to avoid withdrawal symptoms, particularly with shorter half-life agents (paroxetine, fluvoxamine, sertraline). 4
• Do not use tricyclic antidepressants (TCAs) due to unfavorable risk-benefit profile, particularly cardiac toxicity. 5

Adjunctive Non-Pharmacological Strategies

• Breathing techniques, progressive muscle relaxation, grounding strategies, visualization, and mindfulness are useful adjunctive anxiety management strategies. 5
• Regular cardiovascular exercise and activities of enjoyment. 5
• Provide psychoeducation to family members about anxiety symptoms and treatment. 5