From the Guidelines
Atomoxetine can be used as an augmentation strategy for patients who have had an inadequate response to SSRI treatment, with a recommended starting dose of 18-25mg daily and a target dose of 80mg daily. When adding atomoxetine to an SSRI regimen, it is essential to start with a low dose and gradually increase it to minimize potential side effects, as atomoxetine is primarily metabolized through the cytochrome P450 2D6 (CYP2D6) pathway, which can be affected by some SSRIs 1. The combination of atomoxetine and SSRI works by complementary mechanisms, with SSRIs increasing serotonin levels and atomoxetine primarily inhibiting norepinephrine reuptake, potentially addressing both serotonergic and noradrenergic aspects of depression or anxiety.
Key Considerations
- Start atomoxetine only after the patient has been stabilized on the SSRI
- Monitor for increased blood pressure, heart rate, insomnia, dry mouth, and decreased appetite
- Allow 2-4 weeks at therapeutic doses to evaluate effectiveness
- Discontinue if no meaningful benefit is observed after 6-8 weeks at therapeutic doses
- Be aware of the potential risk of suicidal ideation, especially in children and adolescents, and closely monitor patients for suicidality, clinical worsening, and unusual changes in behavior 1
Patient Selection
This approach may be particularly helpful for patients with comorbid ADHD symptoms or those with depression characterized by fatigue, concentration difficulties, or psychomotor retardation. However, it is crucial to carefully evaluate the potential benefits and risks of atomoxetine augmentation, especially in patients with preexisting cardiovascular diseases or significant cardiac abnormalities 1.
Dosing and Administration
The maximum recommended dosage of atomoxetine is 1.4 mg/kg/day or 100 mg/day, whichever is lower, and it is essential to follow a sequential, weight-based approach for titration 1. Additionally, be aware that approximately 7% of the population are poor metabolizers of atomoxetine, which can lead to significantly higher plasma levels and longer half-lives, increasing the risk of adverse effects 1.
From the Research
Atomoxetine as an Augmenting Agent to SSRI
- Atomoxetine is a selective norepinephrine reuptake inhibitor that has been studied as a potential augmenting agent to selective serotonin reuptake inhibitors (SSRIs) in the treatment of various conditions, including attention-deficit hyperactivity disorder (ADHD) and depression 2, 3.
- In a study examining the addition of atomoxetine to sertraline in patients with major depressive disorder, no significant difference was found in symptom severity or remission rates between the atomoxetine and placebo groups 4.
- However, another study found that adjunctive atomoxetine to SSRIs or SNRIs can be effective in reducing symptoms of anxiety in adult patients with comorbid ADHD and partially responsive generalized anxiety 5.
Mechanism of Action and Potential Benefits
- Atomoxetine's mechanism of action is thought to be related to its selective inhibition of presynaptic norepinephrine reuptake in the prefrontal cortex 2.
- The addition of atomoxetine to SSRIs may provide a novel therapeutic approach to depression by targeting residual symptoms not well treated by SSRIs alone, and reducing side effects such as sexual dysfunction 6.
- Atomoxetine has a negligible risk of abuse or misuse and is not a controlled substance in the US, making it a useful option for patients at risk of substance abuse or who do not wish to take a controlled substance 2, 3.
Safety and Tolerability
- Atomoxetine is generally well tolerated, with common adverse events including headache, abdominal pain, decreased appetite, vomiting, somnolence, and nausea 2, 3.
- The majority of adverse events are mild or moderate, and few patients discontinue atomoxetine treatment due to adverse events 2, 3.
- Monitoring for pulse, blood pressure, and weight changes is recommended when using atomoxetine, particularly in patients with pre-existing medical conditions 5.