What are the recommendations for managing suicidal risk in patients with a history of suicidal ideation or attempts who are taking Rexulti (brexpiprazole)?

Managing Suicidal Risk in Patients Taking Rexulti (Brexpiprazole)

Critical FDA Warning

Brexpiprazole carries a boxed warning for increased suicidal thoughts and behaviors in children, adolescents, and young adults (age <25 years), with 14 additional cases per 1,000 patients treated compared to placebo in those under 18, and 5 additional cases per 1,000 in those aged 18-24. 1

The FDA mandates close monitoring for clinical worsening and emergence of suicidal thoughts, particularly during initial months of therapy and at dosage changes. 1

Pre-Treatment Risk Assessment

Before initiating brexpiprazole in patients with suicidal history, conduct a comprehensive suicide risk assessment including: 2

• Self-directed violence history (prior attempts, frequency, lethality, recency) 2
• Current psychiatric conditions (depression severity, bipolar disorder, psychotic symptoms) 2
• Access to lethal means (firearms, medications, other methods) 2
• Social determinants (unemployment, divorce/separation, social isolation, childhood adversity) 2
• Physical health conditions and demographic characteristics 2

Use validated screening tools: 2

• Columbia Suicide Severity Rating Scale Screener (general and high-risk populations)
• Beck Scale for Suicidal Ideation (high-risk populations)
• Patient Health Questionnaire-9 (general population)

Immediate Psychotherapeutic Intervention

Initiate cognitive behavioral therapy (CBT) focused on suicide prevention immediately upon starting brexpiprazole in patients with suicidal history—this is the single most evidence-based intervention, reducing suicide attempts by 32% in adults with recent suicidal behavior. 2

CBT should: 2, 3

• Target suicidal thoughts through cognitive restructuring
• Develop alternative coping strategies
• Occur weekly initially for patients with suicidal behavior within past 6 months
• Include problem-solving therapy components

Safety Planning Requirements

Implement these mandatory safety interventions: 4, 3

• Remove all lethal means immediately, including all medications from the home that could be used in overdose 4
• Establish third-party medication monitoring where a responsible family member controls and dispenses brexpiprazole, reporting behavioral changes immediately 4
• Develop a written crisis response plan identifying warning signs, coping skills, social support contacts, and emergency resources 2, 4
• Never use "no-suicide contracts"—these have no empirical evidence and create false reassurance 4, 3

Monitoring Protocol

Initial 4 Weeks (Highest Risk Period)

Monitor weekly for: 1

• Emergence or worsening of suicidal ideation using validated scales 2, 3
• Clinical worsening of depression
• Behavioral changes (agitation, irritability, impulsivity)
• Akathisia (which can increase anxiety and suicidal thoughts with aripiprazole-class medications) 5

Ongoing Monitoring

• Weeks 1-4: Weekly appointments 4
• Weeks 5-12: Bi-weekly appointments 4
• Months 4-12: Monthly appointments with systematic suicidal ideation screening at every visit 4, 3

Family/Caregiver Involvement

Counsel family members or caregivers to: 1

• Monitor for behavioral changes
• Alert healthcare provider immediately of worsening mood or suicidal statements
• Control medication access
• Remove lethal means from the home

High-Risk Subgroups Requiring Heightened Vigilance

Patients with these characteristics require intensified monitoring when prescribed brexpiprazole: 6, 7

• Prior severe psychiatric illness (especially depression or bipolar disorder) 6
• History of substance use disorder 6
• Traumatic brain injury history 6
• Female gender, divorced/separated, unemployed 7
• Significant childhood adversity 7
• Longer duration or greater severity of current depressive episode 7

When to Discontinue Brexpiprazole

Consider changing the therapeutic regimen, including discontinuing brexpiprazole, in patients whose depression is persistently worse or who are experiencing emergent suicidal thoughts or behaviors. 1

Immediate discontinuation and psychiatric hospitalization are indicated for: 4, 3

• Development of specific suicide plan with intent to act
• Acute worsening of symptoms despite interventions
• Active suicidal ideation with functional decline

Adjunctive Pharmacological Considerations

If suicidal ideation emerges or worsens despite brexpiprazole continuation: 2, 3

• Consider ketamine infusion for rapid (within 24 hours), short-term reduction of suicidal ideation in patients with major depressive disorder (weak recommendation, insufficient evidence for reducing actual attempts) 2, 3
• For schizophrenia/schizoaffective disorder with suicidal ideation: Consider clozapine to reduce suicide attempt risk 2

Follow-Up Communications

Implement periodic caring communications (postal mail or text messages) for 12 months following any crisis or hospitalization—this low-burden intervention reduces suicide attempt risk. 3

Critical Timing Consideration

Approximately 24% of suicide attempts occur within 0-5 minutes of deciding, and the greatest risk for new attempts occurs in months following an initial attempt—emphasizing the critical importance of immediate lethal means restriction and close follow-up. 3