How should a 44-year-old woman with depression (Major Depressive Disorder), Attention Deficit Hyperactivity Disorder (ADHD), and a history of breast cancer who presents with new onset memory problems, executive function deficits, apathy, and high fatigue be treated?

Treatment Approach for a 44-Year-Old Woman with Depression, ADHD, History of Breast Cancer, and New Cognitive Symptoms

This patient requires immediate assessment for reversible causes of cognitive impairment (anemia, thyroid dysfunction, cardiac dysfunction) and treatment of her depression, as both conditions are likely contributing to her executive dysfunction, apathy, and fatigue—with cognitive behavioral therapy plus SSRI pharmacotherapy as first-line treatment, while simultaneously addressing her ADHD which significantly worsens depression outcomes and increases suicide risk. 1, 2

Step 1: Urgent Assessment for Reversible Medical Causes

Assess for reversible contributing factors of cognitive impairment and optimally treat when possible, as this is the first priority in breast cancer survivors presenting with cognitive difficulties 1:

• Check complete blood count for anemia 1
• Assess thyroid function (TSH, free T4) 1
• Evaluate cardiac function (lipid panel, cardiovascular monitoring as indicated) 1
• Review all current medications for those contributing to cognitive impairment or mood symptoms, with consideration for dose adjustment or substitution 2
• Screen for sleep disturbance and pain, as these impact both fatigue and cognition 1

Step 2: Formal Assessment of Depression, Anxiety, and Suicide Risk

Conduct a more probing assessment for depression given her high-risk profile (young age, history of psychiatric disease with ADHD) 1:

• Use Patient Health Questionnaire-9 (PHQ-9) to quantify depression severity 2
• Use Generalized Anxiety Disorder 7-item scale (GAD-7) to assess anxiety 1
• Assess specifically for suicidal ideation and prior attempts, as ADHD comorbidity significantly increases suicide risk—patients with depression plus ADHD have higher rates of suicidal ideation, more suicide attempts, and attempts requiring more medical intervention 3
• Use distress thermometer (scores ≥4 indicate clinically significant distress) 1

Step 3: Cognitive Assessment and Referral

Refer for neurocognitive assessment and rehabilitation, including group cognitive training 1:

• Cognitive impairment in breast cancer survivors is multifactorial and may be related to chemotherapy, surgery/anesthesia, endocrine therapy, or cancer itself 1
• Cognitive rehabilitation strategies and group cognitive training (structured, repetitive practice of tasks requiring mental challenge) have been found helpful at reducing cognitive impairment in breast cancer survivors 1
• The "not paying bills on time" and "not caring" suggest executive dysfunction and apathy, which require formal neuropsychological evaluation 1

Step 4: First-Line Treatment for Depression and Anxiety

Offer cognitive behavioral therapy (CBT) as first-line treatment, with SSRI pharmacotherapy given the severity of symptoms (executive dysfunction, apathy, high fatigue) 1, 2, 4:

Psychotherapy Component:

• CBT or interpersonal therapy should be culturally informed and linguistically appropriate 4
• Combination treatment (CBT + SSRI) is superior to either alone for anxiety disorders and should be offered preferentially 4
• CBT is also recommended for fatigue management 1

Pharmacotherapy Component:

Start sertraline 50 mg daily as the preferred first-line SSRI 4:

• Sertraline has favorable side effect profile and is FDA-approved for major depressive disorder, panic disorder, social anxiety disorder, PTSD, and OCD 4
• If initial anxiety or agitation occurs, consider starting with 25 mg daily as a "test dose" before increasing to 50 mg 4
• Increase dose in 50 mg increments at 1-2 week intervals if inadequate response, up to maximum 200 mg daily 4
• Allow 6-8 weeks for adequate trial, including at least 2 weeks at maximum tolerated dose 4

Alternative first-line options if sertraline not tolerated:

• Escitalopram or citalopram have the least effect on CYP450 enzymes and lowest propensity for drug interactions 4
• Avoid fluoxetine and paroxetine in breast cancer survivors on tamoxifen, as these strongly inhibit CYP2D6 and cause dangerous interactions with tamoxifen 4

Step 5: Address ADHD Comorbidity

The presence of ADHD significantly complicates depression treatment and must be addressed concurrently 3, 5, 6, 7:

• Depression starts at an earlier age in individuals with comorbid ADHD, and the progress of depression treatment changes negatively 3
• ADHD is causally related to MDD, with genetic liability for ADHD increasing odds of MDD by 15% 7
• Adults with ADHD and MDD have higher frequency of generalized anxiety disorder and social phobia 5
• ADHD comorbidity is associated with mixed features, bipolar diathesis, multiple psychiatric comorbidity, and more unstable course 6

Treatment approach for ADHD:

• Once depression is stabilized on SSRI, consider adding stimulant medication for ADHD if symptoms persist
• Monitor closely for treatment-emergent suicidality, especially during first 1-2 weeks after any medication initiation or dose changes 4

Step 6: Fatigue Management

Counsel patient to engage in regular physical activity as this addresses both fatigue and depression 1:

• Physical activity is recommended for fatigue management in breast cancer survivors 1
• Mindfulness-based interventions and yoga are also recommended for depression symptoms in breast cancer survivors 1

Step 7: Monitoring and Treatment Adjustment

Monitor treatment response at 4 weeks and 8 weeks using PHQ-9 2, 4:

• Assess for treatment-emergent suicidality, particularly in first 1-2 weeks after initiation or dose changes 4
• If little improvement after 8 weeks despite good adherence, adjust regimen by:
  • Adding psychological intervention to pharmacotherapy if not already combined 4
  • Switching to different SSRI (escitalopram) or SNRI (venlafaxine) 4
  • One in four patients becomes symptom-free after switching medications 4

Continue SSRI treatment for 4-9 months after satisfactory response for first-episode depression; longer duration (≥1 year) for recurrent episodes 4

Step 8: Integrative Oncology Approaches

Consider mindfulness-based interventions, yoga, or music therapy as adjunctive treatments for depression symptoms in breast cancer survivors 1:

• These interventions are specifically recommended for adults with cancer or history of cancer experiencing depression symptoms 1
• Can be offered during active treatment or post-treatment phases 1

Critical Pitfalls to Avoid

• Don't fail to identify and address underlying medical causes (anemia, thyroid dysfunction, cardiac dysfunction) before attributing all symptoms to psychiatric illness 2
• Don't discontinue SSRI prematurely—full response may take 6-8 weeks; partial response at 4 weeks warrants continued treatment, not switching 4
• Don't abruptly discontinue sertraline—taper when stopping to avoid discontinuation syndrome with dizziness, nausea, and sensory disturbances 4
• Don't underestimate suicide risk—this patient has multiple risk factors (young age, ADHD comorbidity, history of psychiatric disease) requiring close monitoring 1, 3
• Don't ignore the ADHD diagnosis—it significantly worsens depression outcomes and must be addressed for successful treatment 3, 5, 7
• Don't use fluoxetine or paroxetine if patient is on tamoxifen due to dangerous CYP2D6 interactions 4