Varenicline is an alpha 4 beta 2 nicotinic receptor partial agonist with dopaminergic effects, approved for smoking cessation. The complex interactions and modulations of serotonin and nicotine receptors caused by varenicline may cause mania by its serotonin agonist activity and by its release of dopamine in the striatum. We report a case of a varenicline-induced mania with the history of depression.

A 38-year-old female, with the history of depression and have been using sertraline 50 mg/day for a year, admitted for grandiose delusions, decreased need for sleep, increased amount and rapid speech, and agitation. These symptoms began 1 week after she started taking varenicline as prescribed for smoking cessation. Young Mania Score (YMS) was 32. She discontinued sertraline and varenicline after 1 week of use but symptoms of mania continued. The patient smoked about 20 cigarettes a day for more than 10 years. She had a positive history of depression in her family. Her lab work up was unremarkable; including negative urine toxicology and brain CT scan. The patient met DSM-5 criteria for a manic episode and was started on olanzapine 10 mg/day and quetiapine 100 mg/day. The patient's symptoms gradually improved within 1 week with attainment of euthymic mood, improved sleep, and resolution of grandiosity. YMS was 7.

Based on this case it might be suggested that patient's and family's psychiatric history should be assessed cautiously before prescribing varenicline for smoking cessation due to development of mood symptoms.

The authors have not supplied their declaration of competing interest.