Atomoxetine (Strattera)

Atomoxetine (Trade name: Strattera) is a selective norepinephrine reuptake inhibitor (selective NRI) used in the treatment of attention-deficit/hyperactivity disorder.

• Atomoxetine causes inhibition of the norepinephrine (NE) transporter and prevents synaptic clearance of NE, resulting in increased synaptic NE.

Second line for:

• Attention-Deficit/Hyperactivity Disorder (ADHD) (one added benefit of using atomoxetine is that it may also treat any underlying anxiety or depressive symptoms given its “antidepressant” mechanism of action)
  • Response rate: 45% (≥40% improvement) to 60% (≥25% improvement).^[4]
• Atomoxetine is not typically used for other psychiatric disorders or indications.

• Once daily dosing (usually in the morning) is most common 

  • If the patient is a poor CYP 2D6 metabolizer or is taking a drug that's a 2D6 inhibitor, then continue 0.5 mg/kg/day (max 40 mg) for 2-4 weeks before considering any further increase in dose 

• BID dosing and slower titration may improve tolerability (especially appetite, GI side effects, and somnolence)
• Capsules should be swallowed whole

• Atomoxetine comes in oral formulation

• Like most antidepressants (and unlike stimulants):
  • Atomoxetine mMlly over weeks to months
  • Suicidal ideation and behaviours should be monitored for during treatment. Atomoxetine is associated with increased risk of suicide-related behaviours
• Heart rate and and blood pressure at baseline and regularly thereafter, especially with dose increases
• Height and weight plotted on a growth chart
• Baseline liver function tests are not necessary, but should be done at the first signs or symptoms of liver dysfunction

• Treatment with MAOI and for up to 14 days after discontinuation
• Narrow angle glaucoma
• Uncontrolled hyperthyroidism
• Advanced arteriosclerosis
• Known hypersensitivity or allergy
• Pheochromocytoma
• Moderate to severe hypertension
• Symptomatic cardiovascular disease
• Severe cardiovascular disorders

• Monoamine oxidase inhibitors are contraindicated
• Inhibitors of CYP2D6 (e.g. - paroxetine, fluoxetine, bupropion, quinidine) may increase atomoxetine serum concentrations
  • To a much lesser extent, this also occurs with 2C19 inhibitors
• Decongestants (e.g. - pseudoephedrine) may possibly increase blood pressure and heart rate
• QT prolonging agents (e.g. - quetiapine, quinidine) may prolong QTc interval
• Although there is no interaction with stimulants, there is no evidence to support combining a stimulant with atomoxetine in the treatment of ADHD.^[7]
• Beta-2 agonist-induced tachycardia and hypertension can be potentiated by atomoxetine, so this combination should be avoided

• Common side effects of atomoxetine include nausea, dry mouth, insomnia, sedation, fatigue, decreased appetite, tachycardia (mean increase <10 bpm), hypertension (mean increase <4 mmHg), urinary hesitation/retention, constipation, and dizziness.
• Important side effects to inform patients of include sexual dysfunction such as decreased libido

• Serotonin syndrome
• QTc prolongation and adverse cardiac events.^[8]
• Rare cases of liver failure
• Risk of priapism

• Advantages of using atomoxetine for the treatment of ADHD over stimulants include:
  • More continuous coverage throughout the day
  • No potential for drug abuse
  • Less likely to be used for weight loss in an individual with an eating disorder
  • Less concern about growth suppression.^[9]
  • Likely lower risk of exacerbating tics, and may even improve tics.^[10]
  • Less concern about sudden cardiac death (relative to stimulants), though rare cases have been reported.^[11]