Side Effects of Non-Stimulant ADHD Medications
Non-stimulant ADHD medications have distinct side effect profiles that must be carefully considered, especially in patients already taking antidepressants like bupropion and sertraline. 1, 2
Atomoxetine Side Effects
Common Side Effects
- Somnolence and fatigue are the most prominent adverse effects, occurring in a significant proportion of patients and potentially worsening existing tiredness 1, 3
- Decreased appetite and gastrointestinal symptoms (nausea, abdominal pain, constipation) are frequently reported 4, 3
- Dry mouth, though less common than with stimulants 4
- Dizziness and headache occur in some patients 4, 3
Cardiovascular Effects
- Small increases in heart rate and blood pressure are expected, though generally minor and time-limited 5
- These cardiovascular effects are similar in magnitude to stimulants but do not cause clinically significant QTc prolongation or sudden cardiac death at therapeutic doses 5
- Regular monitoring of blood pressure and pulse is required at baseline and during treatment 1
Critical Safety Warnings
- FDA black box warning for increased risk of suicidal ideation in children and adolescents - this is particularly important given your concurrent use of sertraline for depression 1, 2
- Close monitoring for suicidality, clinical worsening, and unusual behavioral changes is essential, especially during the first few months or at dose changes 1, 2
- Full therapeutic effects take 6-12 weeks to develop, unlike stimulants which work within days 1, 6
Drug Interactions
- SSRIs like sertraline can elevate serum atomoxetine levels through CYP2D6 inhibition, requiring potential dose adjustment 1
- The combination of atomoxetine with SSRIs has been specifically studied and shown to be safe and effective for ADHD with comorbid anxiety or depression 1
Guanfacine Side Effects
Common Side Effects (Dose-Related)
- Somnolence (sedation) is the most prominent effect, ranging from 1-39% depending on dose, with higher rates at 3 mg daily 7
- Dry mouth occurs in 7-54% of patients, showing clear dose-response relationship 7
- Fatigue and weakness (asthenia) affect 3-10% of patients 7
- Dizziness occurs in 2-15% of patients 7
- Constipation ranges from 0-15% depending on dose 7
Cardiovascular Effects
- Small decreases in systolic and diastolic blood pressure and heart rate are typical with alpha-2 agonists like guanfacine 5
- Bradycardia and hypotension can occur, requiring cardiovascular monitoring 7, 5
- No clinically significant QTc prolongation has been observed 5
Sexual Side Effects
- Impotence occurs in 1-7% of male patients, increasing with higher doses 7
Serious but Rare Events
- Syncope has been reported 7
- Rare serious cardiovascular events (cardiac fibrillation, heart block, cerebrovascular accident) have been reported postmarketing, though definitive cause-and-effect relationship is unclear 7
Discontinuation Rates
- Dropout rates due to adverse effects increase dramatically with dose: 0% at placebo, 2% at 0.5 mg, 5% at 1 mg, 13% at 2 mg, and 32% at 3 mg 7
- Most common reasons for discontinuation: dry mouth, somnolence, dizziness, fatigue, weakness, and constipation 7
Time Course
- Adverse reactions tend to decrease over time with continued dosing 7
- Guanfacine requires 2-4 weeks for full therapeutic effect 1, 6
Special Considerations for Your Situation
Interaction with Current Medications
- No contraindications exist for combining non-stimulants with bupropion and sertraline 1
- The combination of atomoxetine with SSRIs is specifically recommended for ADHD with comorbid depression 1, 2
- Never use MAO inhibitors with bupropion or any ADHD medication due to severe hypertension risk 8, 1, 2
Depression History Considerations
- Atomoxetine carries heightened suicidality monitoring requirements given your depression history and concurrent SSRI use 1, 2
- Atomoxetine may actually improve depressive symptoms in patients with ADHD and comorbid mood disorders, though with slower ADHD symptom improvement 9
- Guanfacine has no specific warnings regarding depression but its sedating effects could potentially worsen depressive symptoms 7
Comparative Tolerability
Atomoxetine has fewer and less pronounced adverse effects compared to guanfacine and clonidine, making it better tolerated in most patients 6. However, the somnolence and fatigue profile of atomoxetine may be problematic if you already experience low energy from depression 1. Guanfacine's sedating properties might be beneficial if you have sleep disturbances or agitation, but problematic if you need daytime alertness 1, 6, 7.