What medication should be prescribed for a 27-year-old woman with depression, seizure disorder, and obesity, currently taking Keppra (levetiracetam), with a Patient Health Questionnaire-9 (PHQ-9) score indicating moderate to severe depression?

Medication Selection for Depression in a Patient with Seizure Disorder and Obesity

Sertraline is the most appropriate medication choice for this 27-year-old woman with depression, seizure disorder, and obesity who is currently taking Keppra (levetiracetam). 1

Rationale for Sertraline Selection

Safety with Seizure Disorder

• Sertraline is considered relatively safe in patients with seizure disorders 1, 2
• Levetiracetam (Keppra) is considered weight-neutral 3, and adding sertraline will not negatively impact this profile
• Bupropion carries an increased risk of seizures and should be avoided in patients with seizure disorders 4

Weight Considerations

• Sertraline is associated with weight neutrality with long-term use 3, 1
• Mirtazapine is closely associated with weight gain 3, making it a poor choice for a patient with obesity
• Fluoxetine has been associated with short-term weight loss but weight neutrality with long-term use 3

Efficacy for Depression

• The patient's PHQ-9 score of 20 indicates moderate to severe depression requiring pharmacological intervention
• Second-generation antidepressants like sertraline are considered first-line treatment for depression 3
• Sertraline has demonstrated effectiveness for depression in primary care settings 5

Comparison with Alternative Options

Bupropion

• While bupropion is the only antidepressant consistently shown to promote weight loss 3, it is contraindicated in this patient due to:
  • Increased seizure risk, especially concerning in a patient with existing seizure disorder 4
  • FDA label specifically warns about use in patients with seizure disorders 4

Fluoxetine

• Associated with weight neutrality long-term 3
• However, has a greater risk of agitation and overstimulation 3
• More likely to interact with other medications due to long half-life and CYP450 interactions

Mirtazapine

• Consistently associated with weight gain 3, 1
• Would be counterproductive for a patient with obesity
• While effective for depression, the weight gain side effect makes it a poor choice

Dosing and Administration Recommendations

1. Starting dose: 25-50 mg daily 1
2. Administration: Morning dosing to minimize sleep disturbance 1
3. Titration: May increase gradually after 1 week based on response and tolerability
4. Maximum dose: Up to 200 mg daily 1
5. Monitoring: Assess response within 1-2 weeks of starting therapy, with full evaluation at approximately 6 weeks 1

Important Clinical Considerations

• Monitor for potential behavioral changes, as both levetiracetam 6 and antidepressants can affect mood and behavior
• Levetiracetam has been reported to cause psychiatric side effects including behavioral disturbances in some patients 6, but has also shown mood-stabilizing properties in others 7
• Sertraline has shown improvements in anxiety symptoms and quality of life even when depressive symptoms don't immediately improve 5
• Treatment should continue for 4-12 months after satisfactory response for a first episode of major depression 1

Follow-up Recommendations

• Regular assessment using PHQ-9 to track depression symptoms
• Monitor weight at each visit
• If inadequate response after 6-8 weeks of optimal dosing, consider:
  1. Increasing sertraline dose (if tolerated)
  2. Adding cognitive behavioral therapy
  3. Switching to another SSRI with similar weight profile (e.g., citalopram)

This treatment approach prioritizes both the patient's mental health needs and her existing medical conditions (seizure disorder and obesity), selecting the medication with the best safety and efficacy profile for her specific situation.