Does atomoxetine (Strattera) cause low motivation and poor mood?

Atomoxetine and Mood/Motivation Effects

Atomoxetine can cause mood-related side effects including depression, anxiety, and irritability, though these occur in a minority of patients, and the evidence does not specifically identify "low motivation" as a distinct adverse effect. 1

Documented Psychiatric Side Effects

Depression and Mood Changes

• The FDA label reports that depression occurred in 7% of poor CYP2D6 metabolizers versus 4% in extensive metabolizers in adult clinical trials, indicating a metabolizer-dependent risk 2
• Postmarketing surveillance has identified depression and depressed mood as adverse reactions reported after atomoxetine approval 1
• Mood swings led to treatment discontinuation in 0.4% of adult patients in placebo-controlled trials 1

Anxiety and Related Symptoms

• Anxiety was reported as a reason for discontinuation in 0.4% of adult atomoxetine-treated patients 1
• Postmarketing data confirm anxiety as an identified adverse reaction 1
• Irritability occurred in 5% of atomoxetine-treated adults versus 3% of placebo recipients 1

Other Mood-Related Effects

• Libido changes have been documented in postmarketing reports 1
• Atomoxetine carries an FDA black box warning for suicidal ideation in children and adolescents, requiring close monitoring especially during initial treatment months 2, 3
• However, a large meta-analysis of 23 placebo-controlled studies (N=3,883) found no completed suicides and no statistically significant association between atomoxetine and suicidality 4

Clinical Context and Metabolizer Status

CYP2D6 Poor Metabolizers at Higher Risk

• Poor metabolizers experience significantly higher rates of psychiatric adverse effects due to elevated plasma levels and prolonged half-lives 2, 3
• Approximately 7% of the population are poor CYP2D6 metabolizers 2
• In poor metabolizers, atomoxetine has a plasma half-life of 21.6 hours versus 5.2 hours in extensive metabolizers, with 10-fold higher steady-state plasma concentrations 5

Common Non-Psychiatric Side Effects That May Affect Function

• Fatigue occurred in 10% of atomoxetine-treated adults versus 6% in placebo recipients 1
• Somnolence (including sedation) affected 8% of atomoxetine patients versus 5% of placebo patients 1
• Lethargy has been identified in postmarketing reports 1

Important Caveats

• The evidence does not specifically identify "low motivation" as a distinct adverse effect, though fatigue, lethargy, and somnolence could manifest as reduced motivation clinically 1
• Atomoxetine has a slower onset of action (6-12 weeks) compared to stimulants, which may be misinterpreted as lack of effect or worsening motivation during the titration period 2
• The medication may be particularly useful for patients with comorbid anxiety, suggesting it does not universally worsen mood 2, 6
• Most adverse events are mild to moderate, with very low incidence of serious adverse events and few patients discontinuing due to adverse effects 6

Monitoring Recommendations

• Close monitoring for clinical worsening and unusual behavior changes is essential, especially during the first few months of treatment or at times of dose change 2
• Physicians should routinely inquire about mood changes and sexual dysfunction, as patients may be reluctant to report these spontaneously 1
• If mood symptoms emerge, consider checking CYP2D6 metabolizer status, as poor metabolizers have substantially higher risk of psychiatric adverse effects 2