What is the best course of action for a 15-year-old female with Major Depressive Disorder (MDD) and Attention Deficit Hyperactivity Disorder (ADHD) who experiences increased passive suicidal ideation (SI) thoughts after increasing her fluoxetine (Prozac) dose from 20mg to 30mg per day?

Immediate Action: Reduce Fluoxetine Dose and Intensify Monitoring

Given the temporal relationship between the dose increase and worsening suicidal ideation, immediately reduce fluoxetine back to 20mg daily and schedule urgent follow-up within 48-72 hours. 1, 2

Urgent Assessment Required

Evaluate for Akathisia

• Assess specifically for akathisia (motor restlessness, inner tension, inability to sit still), as this adverse effect is strongly associated with fluoxetine dose increases and emergent suicidal ideation. 1, 3
• Akathisia can develop within 1 week of dose escalation and may manifest as severe restlessness with de novo suicidal thoughts. 3
• If akathisia is present, this represents a medication-induced adverse effect requiring immediate dose reduction or discontinuation. 1, 3

Determine Baseline vs. New-Onset SI

• Document whether these suicidal thoughts represent worsening of pre-existing ideation or completely new-onset thoughts since the dose increase. 1
• The FDA label explicitly warns that suicidal ideation may emerge or worsen "especially early during antidepressant treatment and when the dose is adjusted up or down." 2

Medication Management

Dose Reduction Strategy

• Reduce fluoxetine from 30mg back to 20mg immediately, as treatment-emergent suicidal ideation occurred in 14.3% of patients in fluoxetine trials and was associated with dose-related adverse effects. 4
• The long half-life of fluoxetine (4-6 days for fluoxetine, 4-16 days for active metabolite norfluoxetine) means plasma levels will decrease gradually, minimizing abrupt withdrawal effects. 2
• If suicidal ideation is severe, new-onset, or accompanied by akathisia, consider temporary discontinuation of fluoxetine entirely. 1

Do NOT Prescribe Benzodiazepines

• Avoid benzodiazepines or other medications that reduce self-control, as these can potentially disinhibit some individuals and worsen suicidal risk. 1

Monitoring Protocol

Immediate Follow-Up Schedule

• Schedule follow-up within 48-72 hours, then weekly for the first month after any dose change. 1, 2
• The FDA label mandates that families and caregivers monitor for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, worsening depression, and suicidal ideation "on a day-to-day basis, since changes may be abrupt." 2

Third-Party Monitoring

• Ensure family members or caregivers can report any unexpected mood changes, increased agitation, or emergent suicidal thoughts between appointments. 1
• Instruct caregivers that symptoms may be "severe, abrupt in onset, or were not part of the patient's presenting symptoms" and require immediate reporting. 2

Safety Planning

• Implement immediate safety planning including removal of lethal means (medications, firearms, sharp objects) and establishing 24/7 emergency contacts. 1
• Provide crisis hotline numbers and ensure the patient and family know when to go to the emergency department.

ADHD Medication Considerations

Atomoxetine Warning

• If considering atomoxetine for ADHD management, be aware that it carries a black-box warning for suicidal ideation in children and adolescents, with increased risk particularly after dose increases. 5, 6
• Seven Italian children developed suicidal ideation or self-harming specifically after atomoxetine dose increases. 6
• All children treated with atomoxetine require close monitoring for suicidality, clinical worsening, and unusual behavior changes, especially during the first few months or at dose changes. 5

Stimulant Medications

• Methylphenidate or amphetamine-based stimulants remain first-line for ADHD and do not carry the same suicidality warnings as atomoxetine. 5
• Consider optimizing ADHD treatment with stimulants rather than adding atomoxetine in this clinical context. 5

Critical Caveats

Fluoxetine's Relative Safety Profile

• Despite the suicidality risk, fluoxetine has lower lethal potential in overdose compared to tricyclic antidepressants, making it relatively safer for patients with suicidal risk once stabilized. 1
• The FDA black-box warning requires balancing the risk of suicidality against the clinical need for depression treatment. 1

Risk Factors for Treatment-Emergent SI

• Female gender, younger age, severe depression, drug abuse, and melancholic features increase risk for treatment-emergent suicidal ideation. 4, 7
• Emergence of activation symptoms (agitation, restlessness, anxiety) and overall symptomatic worsening independently predict emergence of suicidal ideation. 4

CYP2D6 Considerations

• Fluoxetine inhibits CYP2D6 and can convert normal metabolizers to poor metabolizers, potentially increasing drug levels and adverse effects. 5, 2
• If the patient is taking other medications metabolized by CYP2D6 (including some ADHD medications), this may compound adverse effects. 5, 2

Documentation Requirements

• Document all assessments of suicidal ideation, presence or absence of akathisia, safety planning interventions, and medication changes at every visit. 1
• Record specific instructions given to patient and family regarding warning signs and emergency procedures. 1