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Varenicline is a smoking cessation agent. Varenicline acts as a partial agonist of α4β2 neuronal nicotinic acetylcholine receptor and prevents nicotine binding to the same. It also causes dopamine (DA) stimulation that decreases craving and symptoms of dependence. A 40-year-old male diagnosed with alcohol and nicotine dependence syndrome was treated with 1 mg of varenicline for 3 days. Patient developed episodes of transient delirium within 15-30 min after administration of varenicline. Patient was disoriented and did not respond relevantly. Patient would have disorientation and would respond irrelevantly and was unable to recall the event completely. There were no features suggestive of seizures. The episodes resolved after the medication was stopped. Varenicline, with its partial agonistic effect on nicotinergic receptors, stimulates the release of multiple neurotransmitters including DA. DA dysregulation is probably responsible for the development of neuropsychiatric adverse reactions due to varenicline. This is the first case report to the best of our knowledge reporting varenicline induced dilirium. In this case, the adverse event was found in an alcohol and nicotine dependent patient undergoing treatment. It is essential to monitor uncommon adverse effects as this can cause significant morbidity.

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