Varenicline-Induced Manic Episode in a Patient With Bipolar Disorder

To The Editor: We report a case of a manic episode in a patient with a history of bipolar disorder who was started on varenicline for smoking cessation. The case raises the possibility of inducing a manic episode with varenicline and using caution when prescribing it to patients with bipolar disorder.

Varenicline was approved by the Food and Drug Administration (FDA) in 2006 for smoking cessation. Varenicline binds with high affinity and selectivity at alpha4beta2 neuronal nicotinic acetylcholine receptors. Its efficacy is the result of its activity at a subtype of the nicotinic acetylcholine receptor, where its binding produces agonist activity while simultaneously preventing nicotine binding to the alpha4beta2 receptors. During abstinence, varenicline stimulates low-level dopamine release by binding to alpha4beta2 receptors located on dopamine neurons (1) .

Agitation, aggression, and mood swings were reported as infrequent psychiatric adverse reactions in the preclinical studies for FDA approval of verenicline. In addition, euphoric mood, agitation, and psychosis were reported as rare psychiatric adverse reactions.

Several studies have shown that centrally active cholinergic agonists possess antimanic properties. Imbalance in cholinergic and adrenergic tone has been postulated in the pathophysiology of bipolar disorder, with relative cholinergic hypoactivity being implicated in the pathophysiology of mania (2) . The release of catecholamines, such as dopamine, was likely related to the induction of mania in our patient.

Due to the high rate of smoking in bipolar disorder patients, smoking cessation agents may be used in a great number of patients with the disorder. However, our findings suggest a possible link between the onset of manic symptoms and treatment with varenicline in a patient with bipolar disorder. In this case, there was a temporal relationship between the beginning of therapy and the onset of symptoms. There were no other medication changes in our patient’s regimen. A MEDLINE literature search revealed no case reports or studies regarding manic symptoms with varenicline. Our case highlights the need to use caution when prescribing the drug to patients with bipolar disorder.