What is the recommended treatment approach for a patient with comorbid bipolar disorder and Attention Deficit Hyperactivity Disorder (ADHD)?

Treatment of Comorbid Bipolar Disorder and ADHD

Stabilize bipolar disorder first with a mood stabilizer before addressing ADHD symptoms, then add stimulant medication or atomoxetine once mood is controlled. 1

Critical Treatment Sequencing

Mood stabilization must be achieved before initiating any ADHD treatment. 2 Treating unstabilized bipolar disorder with ADHD medications significantly increases the risk of mood destabilization and can trigger manic or mixed episodes. 2

Step 1: Establish Mood Stability

• Initiate treatment with lithium or divalproex as first-line mood stabilizers. 1, 3, 4
• For acute mania, combination therapy with lithium or valproate plus an atypical antipsychotic (olanzapine, risperidone, quetiapine, aripiprazole) is most effective, with approximately 20% more patients responding compared to monotherapy. 5, 6
• Maintain the mood stabilizer regimen for 12 to 24 months minimum, as most youths with bipolar disorder require ongoing medication therapy to prevent relapse. 1
• Monitor for adequate mood control using standardized rating scales before proceeding to ADHD treatment. 1

Step 2: Address ADHD After Mood Stabilization

Once mood symptoms are adequately controlled on a mood stabilizer regimen, stimulant medications may be added for ADHD symptoms. 1

First-Line ADHD Treatment Options:

For patients with well-stabilized bipolar disorder:

• Low-dose mixed amphetamine salts are safe and effective for comorbid ADHD once mood is stabilized with divalproex, based on a randomized controlled trial of 40 bipolar children and adolescents. 1
• Stimulants should only be considered after complete mood stabilization and carry significant risks if mood is not controlled. 2

For patients with concerns about mood destabilization or substance abuse history:

• Atomoxetine is the preferred first-line ADHD medication, providing effective symptom control without exacerbating mood instability. 2
• Start atomoxetine at 40 mg daily and titrate to target dose of 80-100 mg daily. 2, 7
• Atomoxetine achieves full therapeutic effect within 4-6 weeks and provides "around-the-clock" symptom control. 2
• Screen for bipolar disorder prior to initiating atomoxetine, as required by FDA labeling. 7

Alternative non-stimulant options:

• Extended-release guanfacine or clonidine may be considered as second-line treatment, addressing both ADHD symptoms and emotional dysregulation with minimal risk of triggering mood episodes. 2

Maintenance Strategy

Continue the mood stabilizer regimen indefinitely while treating ADHD. 1 The use of stimulants for comorbid ADHD does not affect relapse rates when mood stabilizers are maintained. 1

• Over 90% of adolescents who were noncompliant with lithium treatment relapsed, compared to 37.5% relapse rate for those compliant with treatment. 1
• The regimen needed to stabilize acute mania should be maintained for 12 to 24 months minimum, with many individuals needing lifelong therapy. 1

Critical Monitoring Requirements

Assess atomoxetine effectiveness after 6-8 weeks at therapeutic dose using standardized ADHD rating scales. 2

Monitor at each visit:

• Suicidal ideation (atomoxetine carries FDA black box warning for suicidality). 7
• Mood symptoms for signs of destabilization or emergence of mania. 7
• Blood pressure and heart rate (atomoxetine can increase heart rate by 5-9 beats/minute). 7
• Appetite and weight changes. 2, 7

For lithium therapy:

• Baseline complete blood count, thyroid function tests, urinalysis, blood urea nitrogen, creatinine, serum calcium, and pregnancy test in females. 1
• Regular monitoring of lithium levels, renal and thyroid function, and urinalyses once stable dose obtained. 1

Common Pitfalls to Avoid

Never initiate ADHD treatment before achieving mood stability. 2 This is the most critical error and significantly increases risk of mood destabilization.

Do not use antidepressants as monotherapy in bipolar disorder, as they are not recommended and may trigger manic episodes. 4

Avoid benzodiazepines for anxiety management in this population due to heightened risk of behavioral disinhibition and reduced self-control. 2

Do not assume a single medication will treat both conditions effectively. 8 Comorbid ADHD predicts poorer response to bipolar treatment, necessitating adequate mood control first before addressing ADHD symptoms. 1, 2

Educate patients and families about early signs of mood episodes so treatment can be resumed promptly if needed. 1