Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts orBehaviors in the Pooled Placebo-Controlled Trials of Antidepressants in
Pediatric* and Adult PatientsAge Range (years) Drug-Placebo Difference in Number of Patients with Suicidal
Thoughts or Behaviors per 1000 Patients Treated
Increases Compared to Placebo
<18 14 additional patients
18-24 5 additional patients
Decreases Compared to Placebo
25-64 1 fewer patient
*ZULRESSO is not approved in pediatric patients.
ZULRESSO does not directly affect monoaminergic systems. Because of this and thecomparatively low number of exposures to ZULRESSO, the risk of developing suicidal thoughtsand behaviors with ZULRESSO is unknown. Consider changing the therapeutic regimen,including discontinuing ZULRESSO, in patients whose depression becomes worse or whoexperience emergent suicidal thoughts and behaviors.
6 ADVERSE REACTIONS
The following adverse reactions are discussed in more detail in other sections of the labeling:
• Excessive Sedation and Sudden Loss of Consciousness [see Boxed Warning,Warnings and Precautions (5.1)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in clinical trials of a drug cannot be directly compared to rates in the clinical trials ofanother drug and may not reflect the rates observed in clinical practice.
The data described below reflect exposure to ZULRESSO in 140 patients with postpartumdepression (PPD). A titration to a target dosage of 90 mcg/kg/hour was eva luated in 102 patientsand a titration to a target dose of 60 mcg/kg/hour was eva luated in 38 patients [see ClinicalStudies (14)]. Patients were then followed for 4 weeks.
The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) weresedation/somnolence, dry mouth, loss of consciousness, and flushing/hot flush (Table 2).
Adverse Reactions Leading to Discontinuation, Dosage Interruption, or Dosage ReductionIn the pooled placebo controlled-studies, the incidence of patients who discontinued due to anyadverse reaction was 2% of ZULRESSO-treated patients compared to 1% of placebo-treatedpatients. The adverse reactions leading to treatment discontinuation in ZULRESSO-treated patients were sedation-related (loss of consciousness, vertigo, syncope, and presyncope) orinfusion site pain.
In the pooled placebo controlled-studies, the incidence of patients who had an interruption orreduction of the dosage due to any adverse reaction was 7% of ZULRESSO-treated patientscompared to 3% of placebo-treated patients. The adverse reactions leading to dose reduction orinterruption in ZULRESSO-treated patients were sedation-related (loss of consciousness,syncope, somnolence, dizziness, fatigue), infusion site events, changes in blood pressure, ormedication error due to infusion pump malfunction. Three ZULRESSO-treated patients who hada dosage interruption because of loss of consciousness subsequently resumed and completedtreatment after resolution of sym