A 20‑year‑old patient taking Viibryd (vilazodone) reports new‑onset aggression toward others; how should this be managed?

Discontinue Viibryd Immediately and Evaluate for Serotonin Syndrome

Stop vilazodone (Viibryd) immediately—this antidepressant is directly linked to aggression, agitation, and serotonin syndrome even in single-drug exposures, and the FDA black-box warning specifically highlights new or worsening irritability and aggressive behavior as emergent suicidal/behavioral symptoms requiring urgent intervention. 1, 2, 3

Immediate Safety Assessment

• Screen for serotonin syndrome using the Hunter Criteria: look for agitation, tremor, hyperreflexia, clonus, diaphoresis, tachycardia, hyperthermia, and mydriasis 2, 3
• Vilazodone causes serotonin syndrome in 39% of overdoses and frequently produces severe agitation even at therapeutic doses due to its dual SSRI/5-HT1A agonist mechanism 2, 3
• Document specific aggressive behaviors: frequency, triggers, targets (people vs. property), whether reactive or proactive, and any warning signs the patient recognizes 4

Why Vilazodone Is the Culprit

• The FDA label explicitly warns that antidepressants increase risk of "acting aggressive, being angry or violent" and "new or worse irritability"—these are boxed-warning symptoms requiring immediate clinical action 1
• Research demonstrates vilazodone produces agitation in 10% of exposures and causes more severe serotonergic toxicity than traditional SSRIs because it raises synaptic serotonin more rapidly 2, 3
• Unlike other SSRIs, vilazodone frequently causes single-substance serotonin syndrome without co-ingestants, with symptoms lasting >24 hours in 14% of cases 2, 3

Discontinuation Protocol

• Taper vilazodone gradually over 1–2 weeks to avoid discontinuation syndrome (irritability, agitation, dizziness, sensory disturbances) 1
• Reduce by 10 mg every 3–4 days: 40 mg → 30 mg → 20 mg → 10 mg → stop 1
• Monitor daily for worsening aggression, suicidal ideation, or withdrawal symptoms during the taper 1

Aggression Management During Transition

Behavioral De-escalation (First-Line)

• Set clear, respectful limits: "Safety comes first. If you're having a hard time staying safe or controlling your behavior, we will need to [specific consequence]." 4
• Teach self-control strategies: identify specific triggers, practice distraction techniques, use self-initiated time-out, and rehearse assertive (not aggressive) communication 4, 5
• Offer realistic choices to restore sense of control: "Instead of [aggressive behavior], what else could you do? Would [alternative] help?" 4

Pharmacologic Management (If Behavioral Interventions Fail)

• For acute agitation: benzodiazepines (lorazepam 1–2 mg PO/IM) are first-line for psychiatric causes of agitation in young adults 4
• Avoid antipsychotics unless psychosis is present—they carry metabolic, endocrine, and extrapyramidal risks and are not indicated for antidepressant-induced aggression 4, 5
• Never combine benzodiazepines with vilazodone during the taper due to risk of excessive sedation and paradoxical rage reactions 4, 6

Alternative Antidepressant Selection

• Do not restart another SSRI immediately—allow 1–2 weeks washout to assess whether aggression resolves off vilazodone 1
• If depression requires ongoing treatment after washout, consider bupropion (no serotonergic activity, lower aggression risk) or mirtazapine (sedating, may reduce agitation) 1
• Screen for bipolar disorder before starting any new antidepressant, as antidepressant-induced aggression can signal underlying mood dysregulation or mania 4, 5

Monitoring and Follow-Up

• Weekly visits during the first month off vilazodone to track aggression frequency, mood stability, and emergence of withdrawal symptoms 4
• Document each aggressive episode: date, time, trigger, duration, intervention used, and patient's ability to regain control 4
• Notify family/caregivers of the medication change and instruct them to report new or worsening aggression, suicidal statements, or self-harm behaviors immediately 1

Critical Pitfalls to Avoid

• Do not dismiss this as "just a side effect"—the FDA boxed warning classifies new aggression as a potentially life-threatening behavioral emergency requiring immediate intervention 1
• Do not add mood stabilizers or antipsychotics before stopping vilazodone—polypharmacy will obscure the cause and worsen outcomes 5, 7
• Do not use antihistamines (diphenhydramine, hydroxyzine) for agitation—they cause paradoxical rage reactions in young adults 4, 6
• Do not abruptly stop vilazodone—sudden discontinuation can precipitate severe withdrawal agitation and suicidality 1