Treatment of ADHD with Comorbid Bipolar Disorder
Stabilize bipolar disorder FIRST with mood stabilizers (lithium or valproate) before addressing ADHD symptoms, then add low-dose stimulants only after achieving mood stability. 1
Step 1: Achieve Mood Stabilization
- Initiate mood stabilizer monotherapy as the absolute priority before considering any ADHD treatment 1, 2
- Valproate (divalproex) is preferred for mixed or dysphoric mania, while lithium is preferred for classic euphoric mania 1
- Allow 6-8 weeks at adequate doses to assess response before making medication changes 2
- If monotherapy fails, combine lithium plus valproate as the foundation regimen 1
- Add atypical antipsychotics (quetiapine, risperidone, aripiprazole) if mood symptoms persist despite adequate mood stabilizer trials 1, 3
Step 2: Address ADHD Only After Mood Control
Critical timing principle: Stimulants must NEVER be initiated until bipolar symptoms are adequately controlled on mood stabilizers. 1, 2
Stimulant Treatment (Preferred Option)
- Low-dose mixed amphetamine salts are safe and effective once mood is stabilized with divalproex, based on randomized controlled trial evidence in 40 bipolar youth with ADHD 1
- Methylphenidate is also appropriate after mood stabilization 1
- Start with lower doses than typical ADHD treatment to minimize risk of mood destabilization 1
Non-Stimulant Alternatives (Consider First-Line in Specific Contexts)
- Atomoxetine is preferred if substance abuse history exists, as it is an uncontrolled substance with lower abuse potential 1, 4
- Screen for bipolar disorder before initiating atomoxetine, as FDA labeling specifically requires this 4
- Atomoxetine requires 6-12 weeks for full effect versus rapid onset with stimulants 1
- Alpha-2 agonists (clonidine, guanfacine) are alternatives with "around-the-clock" effects and may be preferred with comorbid sleep disorders or tics 1
Step 3: Long-Term Maintenance
- Continue the mood stabilizer regimen that achieved stability for 12-24 months minimum 1
- Most patients require lifelong mood stabilizer therapy, as >90% of non-compliant patients relapse versus 37.5% of compliant patients 1, 2
- Stimulants for ADHD do not increase relapse rates when mood stabilizers are maintained 1
- Never discontinue lithium abruptly, as withdrawal within 6 months carries extremely high relapse risk 1, 2
Critical Monitoring Parameters
- Assess mood symptoms, ADHD symptoms, and medication side effects at every visit 2
- Monitor for treatment-emergent mania or hypomania when adding ADHD medications 4
- Track weight, blood pressure, pulse, and metabolic parameters given high rates of metabolic syndrome (37%) and obesity (21%) in bipolar disorder 3
- Laboratory monitoring for mood stabilizers: lithium levels, thyroid function, renal function for lithium; liver function and valproate levels for valproate 1, 5
Common Pitfalls to Avoid
- Never treat ADHD symptoms first or simultaneously with bipolar symptoms - this risks precipitating mania or mixed episodes 1, 2
- Do not use antidepressants as monotherapy in bipolar disorder, as they can trigger mood switches 3
- Avoid premature discontinuation of mood stabilizers - the relapse rate exceeds 90% in non-compliant patients 1, 2
- Do not assume stimulants will destabilize mood once adequate mood stabilization is achieved - controlled trial data shows safety 1
- Recognize that comorbid ADHD predicts poorer treatment response for bipolar disorder, requiring more intensive management 1
Special Considerations
- Polypharmacy is the norm, not the exception - combination therapy with mood stabilizers plus antipsychotics is often necessary 1, 6
- Use the lowest effective doses to minimize side effects and drug interactions 5
- Atomoxetine dosing must be reduced by 50% in moderate hepatic impairment and 75% in severe hepatic impairment 4
- When using atomoxetine with CYP2D6 inhibitors (paroxetine, fluoxetine), initiate at 0.5 mg/kg/day and increase only if needed after 4 weeks 4