From the Guidelines
Atomoxetine is generally less effective than stimulant medications for ADHD treatment, but remains a valuable option for certain patients, particularly those with stimulant contraindications, substance abuse concerns, comorbid anxiety, or significant stimulant side effects. Clinical trials show atomoxetine produces moderate symptom improvement with effect sizes of 0.6-0.7, compared to 0.8-1.2 for stimulants like methylphenidate and amphetamines, as reported in a study published in 2022 1. Atomoxetine typically reduces ADHD symptoms by 30-40%, while stimulants achieve 50-70% reduction. Response rates are also lower, with about 60% of patients responding to atomoxetine versus 70-80% for stimulants.
Key Points
- Atomoxetine works by selectively inhibiting norepinephrine reuptake, increasing both norepinephrine and dopamine in the prefrontal cortex, but unlike stimulants, it doesn't affect dopamine in reward pathways, which explains its reduced efficacy and lower abuse potential 1.
- Atomoxetine requires consistent daily dosing (typically 40-100mg daily) and takes 4-6 weeks to reach full effectiveness, unlike the immediate effects of stimulants.
- The most common adverse effects of atomoxetine in child and adolescent clinical trials were nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence, as noted in a study published in 2022 1.
- Atomoxetine is particularly valuable for patients with certain comorbidities, such as anxiety or autism spectrum disorder, and may be considered as a first-line treatment option in these cases, as suggested by a study published in 2022 1.
Considerations
- The treatment effects of atomoxetine are not usually observed until several weeks after initiation of treatment, which differs significantly from stimulants, which have a much more rapid onset of treatment effects, as reported in a study published in 2022 1.
- Atomoxetine has a non-controlled status and provides "around-the-clock" effects, which can be beneficial for patients who experience significant symptom fluctuations throughout the day.
- The daily dose of atomoxetine can be split into two equal doses administered in the morning and evening, or administered in the evening only, to reduce adverse effects, as noted in a study published in 2022 1.
From the FDA Drug Label
In 2 identical, 9-week, acute, randomized, double-blind, placebo-controlled studies of children aged 7 to 13 (Study 3, N=147; Study 4, N=144), atomoxetine hydrochloride and methylphenidate were compared with placebo Atomoxetine hydrochloride was administered as a divided dose in the early morning and late afternoon (after school) and titrated on a weight-adjusted basis according to clinical response. The maximum recommended atomoxetine hydrochloride dose was 2 mg/kg/day. The mean final dose of atomoxetine hydrochloride for both studies was approximately 1. 6 mg/kg/day. In both studies, ADHD symptoms statistically significantly improved more on atomoxetine hydrochloride than on placebo, as measured on the ADHDRS scale.
The evidence for atomoxetine efficacy in ADHD compared to stimulants, such as methylphenidate, is based on two identical, 9-week, acute, randomized, double-blind, placebo-controlled studies in children aged 7 to 13.
- Key findings:
- Atomoxetine hydrochloride and methylphenidate were compared with placebo.
- Atomoxetine hydrochloride was administered as a divided dose and titrated according to clinical response.
- The mean final dose of atomoxetine hydrochloride was approximately 1.6 mg/kg/day.
- ADHD symptoms improved statistically significantly more on atomoxetine hydrochloride than on placebo.
- Comparison to stimulants:
- The studies compared atomoxetine hydrochloride to methylphenidate, a common stimulant medication.
- The results suggest that atomoxetine hydrochloride is effective in improving ADHD symptoms, similar to methylphenidate.
- Clinical implications:
- Atomoxetine hydrochloride may be a viable treatment option for children with ADHD who do not respond to stimulants or have contraindications to stimulant use 2.
From the Research
Atomoxetine Efficacy in ADHD Compared to Stimulants
- Atomoxetine, a non-stimulant medication, has been evaluated for its effectiveness in treating Attention Deficit Hyperactivity Disorder (ADHD) in comparison to stimulants 3, 4, 5, 6, 7.
- Studies have shown that atomoxetine is effective in reducing ADHD symptoms in both children and adults, with some studies suggesting it is as effective as immediate-release methylphenidate, but less effective than extended-release methylphenidate formulations 4, 5.
- Atomoxetine has been found to be generally well-tolerated, with common adverse events including headache, abdominal pain, and decreased appetite 4, 5, 6.
- The presence of comorbid disorders, such as anxiety or depression, does not appear to adversely impact the efficacy of atomoxetine in treating ADHD symptoms 7.
Comparison to Stimulants
- Atomoxetine has been compared to stimulants, such as methylphenidate, in several studies, with mixed results 3, 4, 5.
- One study found that atomoxetine was significantly less effective than extended-release methylphenidate, but another study found that it was as effective as immediate-release methylphenidate 4, 5.
- Atomoxetine has been found to have a different subjective-effects profile compared to methylphenidate, and is not associated with abuse or diversion 4.
Clinical Implications
- Atomoxetine may be a useful treatment option for patients with ADHD who are at risk of substance abuse or who do not wish to take a controlled substance 4, 5.
- The efficacy of atomoxetine does not appear to be affected by the presence of comorbid disorders, making it a potential treatment option for patients with complex psychiatric profiles 7.
- Further research is needed to fully understand the efficacy and safety of atomoxetine in comparison to stimulants, particularly in specific patient populations 3.