Can atomoxetine be used to treat a patient complaining of fatigue with mild depression who is currently taking Paxil (paroxetine) 37.5mg daily?

Atomoxetine for Fatigue with Mild Depression in a Patient on Paroxetine

Atomoxetine may be beneficial for treating fatigue in a patient with mild depression who is currently on paroxetine 37.5mg daily, as it has shown efficacy for residual fatigue in depression with a different mechanism of action than SSRIs.

Mechanism and Rationale

• Atomoxetine is a selective norepinephrine reuptake inhibitor that works by inhibiting presynaptic norepinephrine reuptake in the prefrontal cortex 1
• Unlike stimulants such as methylphenidate, atomoxetine has a negligible risk of abuse or misuse and is not a controlled substance 1
• The dopaminergic and noradrenergic action of atomoxetine makes it particularly effective for improving symptoms of fatigue and low energy in patients with depression 2

Evidence for Efficacy in Fatigue with Depression

• A retrospective chart review found that atomoxetine significantly decreased Brief Fatigue Inventory (BFI) scores when used as an adjunctive medication for residual fatigue in patients with major depressive disorder who had improved on conventional antidepressants 3
• In this study, 41.6% of patients had a 50% or greater decrease in BFI scores after treatment with atomoxetine 3
• A systematic review identified atomoxetine as one of the pharmacological treatments that demonstrated reductions in residual fatigue in depression 4
• Medications with dopaminergic and/or noradrenergic action like atomoxetine have been found most effective in improving symptoms of fatigue and low energy in major depressive disorder 2

Dosing and Administration

• The mean effective dose of atomoxetine for fatigue in depression was 42.8±10.6 mg in clinical studies 3
• Atomoxetine can be administered either as a single daily dose or split into two evenly divided doses 1
• Start with a lower dose and titrate up based on response and tolerability

Potential Side Effects and Monitoring

• Common side effects include insomnia, increased anxiety, nausea, and dry mouth 3
• Atomoxetine may cause statistically but not clinically significant increases in heart rate and blood pressure 1
• Monitor for potential drug interactions, as atomoxetine is metabolized by CYP2D6, which is also involved in paroxetine metabolism 1, 5
• Paroxetine is a CYP2D6 inhibitor and may increase atomoxetine exposure, similar to what is observed in poor CYP2D6 metabolizers 1

Considerations for Use with Paroxetine

• When combining atomoxetine with SSRIs like paroxetine, be aware that:
  • Paroxetine may increase atomoxetine levels through CYP2D6 inhibition 1
  • A lower starting dose of atomoxetine may be warranted due to this interaction
  • In previous studies, atomoxetine has been successfully used as an adjunct to SSRIs in 78.6% of cases 3

Alternative Options

• If atomoxetine is not effective or not tolerated, modafinil has shown promise in treating residual fatigue in depression 4, 2
• Psychostimulants like methylphenidate have shown mixed results in treating fatigue but may be considered if other options fail 6
• Non-pharmacological interventions such as exercise and light therapy may also be beneficial as adjunctive treatments 2

Monitoring and Follow-up

• Assess improvement in fatigue using standardized measures like the Brief Fatigue Inventory 3
• Monitor for potential side effects, particularly insomnia and anxiety, which were reported in previous studies 3
• Evaluate for any changes in depression symptoms, as atomoxetine has been shown to further improve Hamilton Depression Rating Scale scores in patients already responding to antidepressants 3