Thoughts and Acts of Aggression/Violence Toward Others Reported in Association with Varenicline

BACKGROUND: Thoughts and acts of aggression/violence toward others have been reported in postmarketing surveillance of varenicline, an aid to smoking cessation. OBJECTIVE: To identify the common characteristics of these thoughts and acts of aggression/violence toward others and assess the likely relationship to varenicline treatment. METHODS: We obtained 78 adverse event reports from the Food and Drug Administration MedWatch database containing medical terms describing possible acts or thoughts of aggression/violence; 4 additional cases were reported in clinical trials, and 3 others came from the published literature. We used psychiatric diagnostic criteria and an adverse event causality assessment tool to identify 26 case reports for study. RESULTS: The selected cases described 10 events with assault, 9 cases of homicidal ideation, and 7 cases of other thoughts or acts of aggression/violence. The most frequent common characteristics were (1) inexplicable and unprovoked event, (2) the victim was anyone nearby, (3) no indication of a prior history of similar behavior in the patient, and (4) early onset of psychiatric adverse effects, often before stopping smoking. Where dechallenge/rechallenge information was available, psychiatric adverse effects resolved in 13/14 (93%) cases after discontinuation. CONCLUSIONS: The clear temporal relationship, lack of prior history of this behavior, and unusual nature of these events strengthens the accumulating scientific evidence that varenicline is associated with thoughts and acts of aggression/violence. We recommend that physicians and pharmacists ensure that all patients are informed of possible psychiatric symptoms of varenicline, including violent and aggressive thoughts. All patients should be advised to contact a health-care provider immediately if these symptoms occur and varenicline should be discontinued without delay.