Is atomoxetine (Strattera) effective for treating depression?

Atomoxetine for Depression

Atomoxetine is NOT approved for the treatment of depression and should not be used as a primary antidepressant therapy. The FDA explicitly states that atomoxetine is approved only for ADHD in pediatric and adult patients and is not approved for major depressive disorder 1.

Regulatory Status and Approved Indications

• Atomoxetine is FDA-approved exclusively for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children, adolescents, and adults 1
• The FDA drug label specifically warns that "Atomoxetine hydrochloride is not approved for major depressive disorder" 1
• Current clinical practice guidelines for depression management do not include atomoxetine among recommended antidepressant options 2

Evidence for Depression Treatment

Limited Research Data

While there is minimal research exploring atomoxetine's potential role in depression:

• One small case series (n=15) showed that atomoxetine augmentation of standard antidepressants resulted in 60% of patients meeting response criteria, with significant improvements in depressive symptoms 3
• However, this was an open-label study without placebo control, examining augmentation rather than monotherapy 3

Mechanism Considerations

• PET imaging studies demonstrate that at clinical doses (300-600 ng/mL plasma), atomoxetine occupies >90% of norepinephrine transporters (NET) and >85% of serotonin transporters (SERT) 4
• This dual transporter occupancy theoretically could provide antidepressant effects, but this has not been validated in controlled trials for primary depression 4

Comorbid ADHD and Depression

The only clinically relevant scenario involves treating ADHD patients with comorbid depressive symptoms:

• In children with ADHD and comorbid mood symptoms, atomoxetine monotherapy effectively treats ADHD symptoms and shows improvement in depressive symptoms, though with slower improvement rates than in ADHD-only patients 5
• Combined atomoxetine/fluoxetine therapy in pediatric ADHD patients with comorbid depression or anxiety showed marked reductions in all symptom clusters, though the specific contribution of atomoxetine to mood improvement could not be isolated without a placebo arm 6

Critical Safety Concerns

The FDA Black Box Warning for suicidal ideation in children and adolescents makes atomoxetine particularly inappropriate for depression treatment:

• Pooled analyses showed 0.4% risk of suicidal ideation in atomoxetine-treated children/adolescents versus 0% in placebo 1
• All patients started on atomoxetine must be monitored closely for suicidality, clinical worsening, or unusual behavioral changes, especially during initial treatment or dose changes 1, 2
• This risk profile is unacceptable when established, effective antidepressants with better safety profiles are available 2

Recommended Approach for Depression

Use evidence-based antidepressants instead:

• Second-generation antidepressants (SSRIs, SNRIs) are first-line therapy for major depressive disorder, selected based on adverse effect profiles, cost, and patient preferences 2
• Common first-line options include citalopram, escitalopram, sertraline, and venlafaxine 2
• These medications have established efficacy with number needed to treat of 7-8 for SSRIs 2

Clinical Bottom Line

Atomoxetine should only be prescribed for its FDA-approved indication of ADHD. If a patient has both ADHD and depression, treat the depression with an established antidepressant (such as an SSRI) and consider atomoxetine specifically for ADHD symptoms if stimulants are contraindicated or ineffective. Do not use atomoxetine as monotherapy or augmentation for primary depression outside of research settings, given lack of approval, limited evidence, and significant safety concerns regarding suicidality 1, 2.