What medication adjustment is recommended for agitation management in a patient with ODD, ASD, and in utero cocaine exposure, taking quetiapine and fluoxetine, to simplify the regimen and reduce polypharmacy risk?

Medication Adjustment for Agitation Management

Reduce or discontinue quetiapine rather than adjusting it, as quetiapine is not guideline-recommended for agitation in pediatric patients with ASD and ODD, and can paradoxically worsen agitation in some patients. 1, 2

Rationale for Quetiapine Reduction

Quetiapine lacks strong evidence for agitation management in this population and carries significant risks:

• Quetiapine can cause paradoxical severe agitation as a direct adverse effect, documented in case reports where withdrawal resolved symptoms and reintroduction reproduced the agitation 2
• For agitated dementia (the condition with the most quetiapine evidence), expert consensus ranks quetiapine only as "high second-line" at 50-150 mg/day, behind risperidone as first-line 3
• The patient's symptoms preceded the fluoxetine decrease, suggesting quetiapine may be contributing to rather than controlling the agitation 2

Simplification Strategy to Reduce Polypharmacy

The most evidence-based approach is to:

1. Taper quetiapine gradually (reduce by 25-50 mg every 3-7 days) while monitoring for symptom changes 4, 5
2. Optimize fluoxetine dosing back to the previous effective dose, as SSRIs are first-line for chronic agitation and have better evidence in neurodevelopmental disorders 1
3. Implement intensive behavioral interventions as the primary treatment modality, which must be attempted before any antipsychotic use 1

If Antipsychotic Remains Necessary

Should behavioral interventions and SSRI optimization fail to control severe, dangerous agitation:

• Risperidone 0.25-0.5 mg/day is the only antipsychotic with first-line evidence for agitation, starting at the lowest dose 1, 3
• This represents a medication switch, not an addition, maintaining the goal of simplification 1
• Risperidone has superior evidence compared to quetiapine for behavioral symptoms across multiple guidelines 1, 3

Critical Safety Considerations

Before any medication adjustment:

• Systematically investigate medical triggers: pain, constipation, urinary retention, infections (especially UTI), and medication side effects 1
• Review all medications for anticholinergic effects that worsen agitation 1
• Document specific agitation triggers using ABC (antecedent-behavior-consequence) charting to identify patterns 1

Common Pitfalls to Avoid

• Do not add another medication to the current regimen, as this increases polypharmacy rather than simplifying it 1
• Do not use benzodiazepines for routine agitation management in this population, as they cause paradoxical agitation in approximately 10% of patients and risk tolerance and cognitive impairment 1, 3
• Do not continue quetiapine indefinitely without clear evidence of benefit, as antipsychotics should be used at the lowest effective dose for the shortest duration 1