What is the best approach to manage worsening anxiety in a 13-year-old girl with a history of Midline Defect Syndrome, Upper Central Incisor Syndrome, pyriform aperture stenosis, congenital nasal stenosis, and recent laboratory results indicating a risk for diabetes mellitus and iron deficiency?

Management of Worsening Anxiety in a 13-Year-Old Girl with Complex Medical History

This 13-year-old girl requires immediate initiation of cognitive-behavioral therapy (CBT) as first-line treatment for her worsening anxiety, combined with urgent treatment of her severe iron deficiency, which can independently worsen anxiety symptoms and must be addressed before considering psychiatric medications. 1, 2

Critical Medical Issues Requiring Immediate Attention

Iron Deficiency Treatment (Priority #1)

• Ferritin of 5 μg/L represents severe iron deficiency that requires immediate supplementation. 2
• Iron deficiency can cause or exacerbate anxiety symptoms, fatigue, and cognitive dysfunction 2
• Start oral iron supplementation immediately (elemental iron 3-6 mg/kg/day divided 1-2 times daily) before attributing all symptoms to primary anxiety disorder 2
• Recheck ferritin in 8-12 weeks to ensure adequate response
• This is a critical pitfall: treating anxiety pharmacologically without correcting iron deficiency may lead to treatment failure 2

Pre-Diabetes Risk

• HbA1c of 5.6% indicates increased diabetes risk per 2018 Diabetes Canada Guidelines
• Counsel on lifestyle modifications (diet, exercise) as anxiety management strategies like CBT can also improve metabolic parameters 1
• Recheck HbA1c in 6-12 months

Rule Out Medical Causes of Anxiety

• TSH is normal (0.60 mIU/L), appropriately ruling out hyperthyroidism as a cause of anxiety symptoms 2
• Mildly elevated potassium (5.4 mmol/L) likely spurious from platelet elevation; no intervention needed unless symptomatic 2
• Her complex midline defect syndrome and history of respiratory issues do not typically cause anxiety symptoms directly 3, 4

First-Line Treatment Algorithm for Anxiety

Step 1: Initiate CBT (Weeks 0-12)

CBT is the first-line treatment for adolescent anxiety with the strongest evidence base, showing large effect sizes (Hedges g = 1.01 for generalized anxiety). 1, 5, 6

• Deliver 12-20 structured sessions targeting cognitive, behavioral, and physiologic dimensions 1, 5
• Core CBT components must include: 1, 5
  • Psychoeducation about anxiety and the anxiety cycle
  • Behavioral goal setting and self-monitoring
  • Relaxation techniques (diaphragmatic breathing, progressive muscle relaxation)
  • Cognitive restructuring to challenge anxious thoughts
  • Graduated exposure therapy (the cornerstone of CBT for anxiety) 5, 6
  • Family interventions and parent training

Step 2: Monitor Response (Weeks 4-6)

• Use standardized rating scales at each visit (GAD-7, SCARED, or AACAP Level 1 Cross-Cutting Symptom Measures) 2, 5
• Assess functional impairment in school, social relationships, and family functioning—not just symptom reduction 5
• Screen for comorbid depression, other anxiety disorders, and suicidal ideation at every visit 1, 2

Step 3: Decision Point at 8-12 Weeks

If adequate response to CBT alone:

• Continue CBT to complete 12-20 sessions 1, 5
• Maintain regular monitoring with standardized scales 5

If inadequate response or severe symptoms:

• Add SSRI pharmacotherapy to ongoing CBT (combination therapy is superior to either alone) 1, 6, 7
• First-line SSRI options with FDA data in adolescents: 1, 7, 8
  • Sertraline: Start 25 mg daily, can adjust weekly, target 50-200 mg/day
  • Fluoxetine: Start 10 mg daily, target 20-40 mg/day
  • Fluvoxamine: Start 25 mg daily (though less commonly used)

Step 4: SSRI Monitoring (If Initiated)

Critical safety monitoring for SSRIs in adolescents: 5, 6

• Assess for suicidal ideation at every visit (pooled absolute risk 1% vs 0.2% placebo; NNH = 143) 5, 6
• Monitor for treatment-emergent adverse events: 7
  • Behavioral activation or agitation
  • Headaches and gastrointestinal symptoms
  • Worsening anxiety symptoms
  • Sleep disturbances
• Weekly visits for first 4 weeks, then every 2 weeks until stable 7

Step 5: Duration of Treatment

• Continue SSRI for 12 months after achieving remission before considering tapering 2
• Choose a stress-free time (e.g., summer break) for medication discontinuation 7
• If symptoms return after taper, strongly consider medication re-initiation 7

Screening for Psychiatric Comorbidities

Anxiety disorders are highly comorbid with other psychiatric conditions, requiring systematic screening: 1, 2

• Depression (most common comorbidity): Use PHQ-9 or similar validated tool 1, 2
• Other anxiety disorders: Separation anxiety, social anxiety, panic disorder often co-occur 1
• ADHD: Can present with restlessness and difficulty concentrating that mimics anxiety 5
• Substance use: Particularly important in adolescents 2
• Obsessive-compulsive disorder: Shares underlying vulnerability with anxiety 1

When to Refer to Psychiatry Immediately

Immediate psychiatric referral is required for: 2

• Suicidal ideation, plan, or self-harm behaviors
• Psychosis or severe agitation
• Symptoms not responding to initial treatment (CBT + SSRI)
• Severe functional impairment preventing school attendance or basic self-care

Special Considerations for This Patient

Her Complex Medical History

• Midline defect syndrome and pyriform aperture stenosis are associated with holoprosencephaly spectrum in some cases 3, 9
• Her normal brain MRI from prior evaluation is reassuring 3, 9
• These anatomic variants do not contraindicate standard anxiety treatment 3, 4

Developmental Context

• Anxiety disorders in adolescent girls are often triggered by school performance worries, appearance concerns, and poor self-esteem 1
• Her 2-year history with recent worsening suggests progression from mild to moderate-severe anxiety 1
• Untreated anxiety leads to significant long-term impairments in social, educational, and mental health outcomes extending into adulthood 5, 6

Critical Pitfalls to Avoid

1. Do not start SSRI before correcting severe iron deficiency 2
2. Do not use benzodiazepines—they lack efficacy data in pediatric anxiety and carry dependence risk 1, 6
3. Do not rely on medication alone—CBT is essential and has the strongest evidence base 1, 5, 6
4. Do not fail to screen for suicidal ideation when using SSRIs 5, 6
5. Do not attribute all symptoms to anxiety without ruling out thyroid disease (already done appropriately in this case) 2