Can an adult with ADHD and anxiety/depression safely take Strattera (atomoxetine) together with Lexapro (escitalopram), and what dosing and monitoring are recommended?

Combining Strattera (Atomoxetine) with Lexapro (Escitalopram) in Adults with ADHD and Anxiety/Depression

Yes, adults with ADHD and comorbid anxiety or depression can safely take atomoxetine (Strattera) together with escitalopram (Lexapro), and this combination is well-established in clinical practice with favorable safety data. 1

Safety Profile of the Combination

Escitalopram has the least effect on CYP450 enzymes compared to other SSRIs, resulting in minimal drug-drug interactions, making it one of the safest SSRIs to combine with atomoxetine. 2, 3

• The combination of atomoxetine and an SSRI has been specifically studied in pediatric populations with ADHD and comorbid depression/anxiety, demonstrating that both medications can be used together effectively 1
• In a randomized trial, atomoxetine combined with fluoxetine (another SSRI similar to escitalopram) was well tolerated, with completion rates and adverse event discontinuation rates similar to atomoxetine monotherapy 1
• There are no clinically significant pharmacokinetic interactions between atomoxetine and escitalopram that would prevent their concurrent use 3

Important Cardiovascular Monitoring

The combination produces greater increases in blood pressure and pulse compared to atomoxetine monotherapy, requiring systematic cardiovascular monitoring. 1, 3

• Measure blood pressure and pulse at baseline before starting either medication 4
• Recheck cardiovascular parameters at each dose adjustment during titration 4
• Continue monitoring blood pressure and pulse at every follow-up visit during maintenance therapy 4

Dosing Recommendations

Atomoxetine (Strattera) Dosing

Start atomoxetine at 40 mg once daily, maintain for at least 7-14 days, then increase to 60 mg daily, and if needed, further increase to 80 mg daily after another 7-14 days. 4

• The maximum recommended dose is the lesser of 1.4 mg/kg/day or 100 mg/day 4, 5
• Dose escalations should not occur more frequently than every 7-14 days 4
• Atomoxetine requires 6-12 weeks to achieve full therapeutic effect, unlike stimulants which work within days—set appropriate expectations with patients about this delayed response timeline. 4, 3
• If the patient is already taking escitalopram, consider starting atomoxetine at the lower end of the dosing range (40 mg daily or less) 5

Escitalopram (Lexapro) Dosing

• Standard starting dose for escitalopram is 10 mg daily, with titration to 20 mg daily if needed for anxiety or depression 3
• Escitalopram can be started first and stabilized before adding atomoxetine, or vice versa, depending on which symptom cluster (ADHD vs. mood/anxiety) is more impairing 3

Serotonin Syndrome Risk and Precautions

Exercise caution when combining two serotonergic drugs by starting the second medication at a low dose, increasing slowly, and monitoring for symptoms especially in the first 24-48 hours after dosage changes. 2, 5

• Monitor for early signs of serotonin syndrome: mental status changes, neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia) 5
• The risk of serotonin syndrome with this combination is significantly lower than with MAOIs, but vigilance is still warranted 3
• Symptoms can arise within 24-48 hours after combining medications or dose changes 5

Absolute Contraindications

Never combine either atomoxetine or escitalopram with MAO inhibitors—this is an absolute contraindication due to severe risk of serotonin syndrome and hypertensive crisis. 2, 3

• A minimum 14-day washout period is required after discontinuing an MAOI before starting either medication 3

Monitoring Requirements During Treatment

Suicidality Screening

Systematically assess for suicidal ideation, clinical worsening, and unusual behavioral changes at every visit, especially during the first few months of treatment or at times of dose changes. 4

• Atomoxetine carries an FDA black box warning for increased risk of suicidal thinking in children and adolescents, and this monitoring applies to adults as well 4, 3
• SSRIs also require suicidality monitoring, particularly in younger adults 2

Additional Monitoring Parameters

• Track height and weight at each visit, as atomoxetine can affect appetite 4
• Assess sleep quality and appetite changes as common adverse effects 4
• Use standardized ADHD rating scales to monitor symptom response 3

Common Adverse Effects

Common side effects of atomoxetine include nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence. 4

• These effects are generally transient and less severe than with alpha-2 agonists 4
• Escitalopram may cause initial anxiety or agitation, which typically resolves within the first few weeks 2
• Watch for early signs of adverse effects including agitation, tremor, insomnia, and autonomic symptoms in the first 24-48 hours after initiation or dose changes 5

Treatment Algorithm

For adults with both ADHD and anxiety/depression, the optimal approach depends on which symptom cluster causes greater functional impairment:

1. If ADHD symptoms are primary and more impairing: Start atomoxetine first, titrate to therapeutic dose (60-100 mg daily), then add escitalopram if mood/anxiety symptoms persist after 6-8 weeks 3

2. If anxiety/depression is severe or primary: Stabilize mood symptoms with escitalopram first, then add atomoxetine for ADHD once psychiatric stability is achieved 3

3. If both are equally impairing: Either medication can be started first, but atomoxetine's 6-12 week onset means escitalopram may show benefit sooner for mood symptoms 4, 3

Follow-Up Schedule

Schedule follow-up at 2 weeks after starting the combination, then monthly once stabilized. 5

• More frequent visits (weekly) may be needed during initial titration to monitor for adverse effects and suicidality 4
• Once stable, quarterly visits are appropriate for ongoing monitoring 3

Important Clinical Pitfalls to Avoid

• Do not assume atomoxetine alone will adequately treat both ADHD and depression—despite its initial development as an antidepressant, evidence does not support efficacy for comorbid depression 3
• Do not abruptly discontinue escitalopram—taper gradually to prevent discontinuation syndrome characterized by dizziness, paresthesias, anxiety, and irritability 2
• Do not rush atomoxetine titration—faster dose escalation can cause behavioral activation, agitation, motor restlessness, and insomnia, particularly in younger patients 4
• Do not overlook the need for psychosocial interventions—pharmacotherapy should be combined with cognitive-behavioral therapy for optimal outcomes in adults with ADHD and comorbid mood/anxiety disorders 3