Atomoxetine Should Not Be Used as Primary Treatment for Mood Disorders
Atomoxetine is not effective for treating mood disorders and should not be prescribed for this indication. Despite being initially developed as an antidepressant, evidence clearly demonstrates it lacks efficacy in treating depression or other primary mood disorders 1.
Evidence Against Use in Mood Disorders
The most definitive guideline evidence states that "despite the initial efforts to develop atomoxetine as an antidepressant, evidence so far does not support efficacy in this symptom domain" 1. This represents a clear conclusion from systematic evaluation of the medication's effects on mood symptoms.
When Atomoxetine May Affect Mood Symptoms
Atomoxetine can be used in specific clinical scenarios involving mood, but only as adjunctive treatment when ADHD is the primary diagnosis:
ADHD with Comorbid Mood Disorders
- Atomoxetine effectively treats ADHD symptoms even when comorbid mood disorders are present, though improvement occurs more slowly than in ADHD-only cases 2
- In children with ADHD and comorbid mood disorders, atomoxetine showed improvement in depressive symptoms after 1 month of treatment, but this appears to be a secondary effect rather than primary antidepressant action 2
- When used in stabilized bipolar disorder patients already on mood stabilizers or antipsychotics, atomoxetine can address comorbid ADHD symptoms 3, 4
Critical Safety Concerns with Bipolar Disorder
Atomoxetine carries significant risk of inducing hypomania or mania in patients with bipolar disorder, even when they are stabilized on mood stabilizers 5, 6. This represents a major contraindication concern:
- Case reports document atomoxetine-induced hypomania in stabilized bipolar patients receiving prophylactic mood stabilizers 6
- In open-label studies of bipolar patients, 2 out of 12 subjects discontinued due to worsening mood symptoms 3
- The medication requires special warnings for emergent psychotic or manic symptoms and bipolar disorder 5
Clinical Algorithm for Decision-Making
If the patient has a primary mood disorder (depression, bipolar disorder) without ADHD:
- Do NOT prescribe atomoxetine 1
- Use evidence-based treatments for mood disorders (antidepressants, mood stabilizers, antipsychotics as appropriate)
If the patient has ADHD with comorbid mood disorder:
- First stabilize the mood disorder with appropriate mood stabilizers or antipsychotics 3, 4
- Only after mood stabilization, consider atomoxetine for ADHD symptoms 4
- Monitor closely for suicidal ideation (especially in children/adolescents), clinical worsening, and manic/hypomanic symptoms 5
- Expect slower ADHD symptom improvement compared to patients without mood comorbidity 2
If the patient has bipolar disorder:
- Exercise extreme caution even after mood stabilization 6
- Close monitoring for (hypo)manic symptoms is mandatory throughout treatment 6, 4
- Consider alternative ADHD treatments if mood instability persists
Monitoring Requirements
When atomoxetine is used in any patient with mood concerns, mandatory monitoring includes 5:
- Suicidal ideation (particularly in children and adolescents during first months of treatment)
- Clinical worsening of mood symptoms
- Emergence of manic or hypomanic symptoms
- Unusual behavioral changes, especially during dose initiation or changes