To the Editor: The selective nicotinic partial agonist varenicline is approved for smoking cessation¹ in more than 30 countries. Freedman² has reported a case of a patient with a schizophrenic exacerbation after initiation of varenicline for smoking cessation. Here we present a case of successful smoking cessation and substantial improvement of negative symptoms in a clinically stable patient with schizophrenia.

Mr. A is a 27-year-old former student with the diagnosis of schizophrenia, paranoid subtype for 4 years. His last admission as an inpatient took place 2 years ago and was due to delusions, visual and tactile hallucinations, and ideas of reference. He had no insight into his disorder and ideas of grandiosity ("the creator and guardian of the light"). By then he had also been a cannabis user (on average 0.5 g per day). No somatic disorders had been reported. He was then put on depot medication which he received every 14 days (risperidone, 37.5 mg). He smoked cigarettes for 5 years, increasing to 30 cigarettes a day over the last 6 months. His Positive and Negative Syndrome Scale (PANSS) negative symptoms score fluctuated between 42 and 45 over this period of time, with a PANSS positive symptoms score of only 8 points. Quitting smoking strategies like group counseling and nicotine replacement therapy via patch were altogether unsuccessful. Therefore, a trial with varenicline added to risperidone was started. The drug was titrated to 2 mg per day over a period of 1 week. It was tolerated well, and he experienced no nausea. After 2 weeks, complete abstinence was achieved (that was confirmed via CO measurement in the expiration air) and maintained for 6 months. Moreover, his PANSS negative score decreased from the second week on varenicline to 22 points. Risperidone and 9-hydroxy-risperidone concentrations remained unchanged.

We report for the first time a successful trial of smoking cessation in a patient with very mild positive but marked negative symptoms which substantially improved during the treatment with varenicline without exacerbation of psychotic symptoms. We interpret this clinical observation by the indirect dopamine releasing properties of varenicline.³ Schizophrenia patients seem to have altered nicotinic acetylcholine receptors and stimulation by nicotine has a positive effect on cognition and other symptoms of schizophrenia, which is thought a transient effect.⁴ Nicotine as a full agonist on nicotinic acetylcholine receptors has a very high affinity for these receptors and a tolerance inducing effect that has not been described for varenicline yet. Since the patient still received risperidone he was probably sufficiently protected from the development of new positive symptoms.

Systematic controlled studies of schizophrenia patients with different predominant symptoms treated with varenicline seem warranted to evaluate its possible risks and advantages in this population.