Could the nicotine receptor partial agonist varenicline moderate manic symptoms in heavy smokers with manic episodes?

To the Editor

Tobacco use seems to be increased in patients with bipolar disorder, especially during manic episodes. However, psychiatric wards usually prohibit cigarette smoking, leading to tobacco withdrawal during admission. If such patients tend to be resistant to conventional medications for bipolar mania and display tobacco withdrawal symptoms, what treatments should be needed?

We report a 42-year-old Taiwanese male who was a heavy smoker with bipolar I disorder who presented with a recent manic episode. He was admitted to a psychiatric ward where smoking was prohibited with an initial Young mania rating scale (YMRS) score of 43. Due to persistent severe symptoms, he was prescribed with high doses of mood stabilizers and antipsychotics, including a daily dose titrated to lithium carbonate 900 mg, valproate 1500 mg, quetiapine 1200 mg, clotiapine 320 mg, haloperidol 20 mg and biweekly risperidone depot 25 mg. After 1 month of treatment, the symptoms still persisted with an YMRS score of 46, and treatment-resistant mania was impressed. He also displayed severe tobacco craving and withdrawal symptoms, with Brief Questionnaire on Smoking Urges (QSU-brief) and Minnesota Nicotine Withdrawal Scale (MNWS) scores of 69 and 26, respectively. Varenicline was added and titrated to 2 mg per day for the tobacco-related symptoms. After 10 days, his QSU-brief and MNWS scores improved to 31 and 8, respectively. His manic symptoms also improved, with a decrease in YMRS score to 18 after 2 weeks of varenicline treatment. The antipsychotics were tapered and clotiapine and haloperidol were discontinued. He was discharged with an YMRS score of 5 after 3 weeks of varenicline treatment.

A systematic review and meta-analysis of varenicline reported no evidence of increased major neuropsychiatric side effects when used for smoking cessation in patients with bipolar disorder and showed its effectiveness (Wu et al., 2016). Cyclical dopamine dysregulation has been proposed to be a central mechanism underlying bipolarity in heavy smokers (Thomson et al., 2015). Varenicline, a nicotine receptor partial agonist, can stabilize nicotinic receptors and regulate rewarding circuits of nicotine through downstream dopaminergic neurons (Stahl, 2013). This mechanism may play a role in dopamine-related manic symptoms.

In our case, we initially used extremely high doses of mania-related medications with a poor response. However, after adding varenicline, the symptoms improved. Taken together with the clinical evidences and pharmacological mechanisms, we suggest that the nicotine receptor partial agonist effect of varenicline plays role in moderating manic symptoms in heavy smokers with manic episodes.