He is still under 300 mg/day dose of the same treatment. Discussion The onset of psychotic depression in this patient after initiation of ZD1839 varenicline treatment

for smoking cessation certainly suggests that varenicline has the capacity to induce depression and psychosis at least in patients with a history of mood disorders. This has been reported in another patient with a documented history of bipolar disorder [Kohen and Kremen, 2007; Pumariega et al. 2008]. Possible mechanisms include Inhibitors,research,lifescience,medical dopaminergic stimulation secondary to agonism of the α4β2 nicotinic receptor. Since the approval of varenicline in May 2006, postmarketing surveillance of it suggests an association between varenicline and increased risk of erratic behavior, agitation, suicidal attempt, depression, psychosis, and severe injuries [Williams et al. Inhibitors,research,lifescience,medical 2007]. Some of the behavioral changes and mood changes seen in patients who use varenicline may be associated with nicotine withdrawal. However, some occurred in people who continued smoking while they were on varenicline medication [Xi, 2010]. Although clinician and patient reports of adverse events associated with varenicline suggest the possibility of serious side effects, controlled studies are required to quantify the degree of risk, distinguish Inhibitors,research,lifescience,medical the side effects of varenicline from the effects of smoking cessation [Gunnell

et al. 2009]. The risk for psychiatric side effects from varenicline could be greatly diminished by screening for family history and past history of serious mood disturbance in individuals who are candidates

for its use in smoking cessation [Pumariega et al. 2008]. Smoking rates are particularly pronounced among persons with a history of anxiety, depression, Inhibitors,research,lifescience,medical bipolar disorder, and psychotic disorder [Ziedonis Inhibitors,research,lifescience,medical et al. 2008]. Providing effective cessation treatment to these individuals is important, but there are limited data on the effectiveness of cessation treatments among persons with these conditions [Hall and Prochaska, 2009]. There may be some explanations for the exacerbation of psychotic depression in our patient. First, it is well known that increased dopaminergic MRIP activity in the brain plays a crucial role in the etiology of psychotic episodes seen in bipolar disorder [Cousins et al. 2009]. Varenicline, with its partial agonistic effect on nicotinergic receptors, stimulates the release of multiple neurotransmitters including dopamine [Benowitz, 2007]. It also increases the release of dopamine from nucleus accumbens. Dopamine dysregulation is probably responsible for the development of neuropsychiatric adverse reactions due to varenicline. Second, our patient was also taking lower doses of amisulpride for the last 3 years. Amisulpride, at low doses, has the potential to block presynaptic dopamine autoreceptors which consequently lead to the frontotemporal dopamine release [Scatton et al. 1997].