Smoking Cessation Drug May Boost Cognition in Schizophrenia

Pam Harrison

March 16, 2017

The smoking cessation drug varenicline (Chantix, Pfizer) appears to enhance cognition in nonsmoking individuals with and those without schizophrenia, new research indicates.

The results also showed that the drug reduced the cognitive impairment typically associated with smoking cessation in individuals with schizophrenia.

"Given the high prevalence of smoking in patients with schizophrenia and some of the associated cognitive deficits found in these patients, having a smoking cessation aid that also targets these cognitive deficits would be ideal," lead author Karolina Kozak, a PhD candidate at the Center for Addiction and Mental Health, Toronto, Ontario, told Medscape Medical News.

The findings were reported in a letter to the editor published online March 10 in Schizophrenia Research.

The current randomized, double-blind, placebo-controlled crossover laboratory study is part of a large clinical initiative undertaken by CAMH researchers that was reported in 2013.

In the earlier study, investigators found that treatment with varenicline attenuated impairments in visuospatial working memory (VSWM), a measure of cognitive performance. The finding emerged after patients with schizophrenia quit smoking.

Cognitive deficits and rates of high smoking among schizophrenia patients are linked to dysregulated nicotinic acetylcholine receptors.

Varenicline is a partial nicotinic acetylcholine receptor agonist. Researchers reasoned it may simultaneously enhance cognition and stop worsening cognition typically associated with tobacco abstinence.

The randomized, double-blind, placebo-controlled, crossover laboratory study included a total of 30 participants, 15 with schizophrenia and 15 nonpsychiatric control persons. Participants received varenicline 0 mg, 0.5 mg, or 1 mg twice a day for 3 days in a counterbalanced manner over 3 consecutive weeks with a 1-week washout period between dose weeks in nonsmoking schizophrenia patients and nonpsychiatric control persons.

"During these weeks, participants would come in for weekly cognitive testing sessions," Kozak noted. The primary outcome was VSWM, as measured using the spatial delay recall task. Results reflect findings from the afternoon of the third cognitive testing session, when varenicline plasma levels were likely at their highest.

"When we correlated varenicline plasma levels to participants' cognitive performance on VSWM tasks, we found some interesting findings," said Kozak.

First, patients with schizophrenia performed better (P < .08) when plasma varenicline levels corresponded to the lower doses of the drug.

For control persons, the reverse was true, in that both VSWM (P = .013) and verbal memory performance (P = .005) were better when varenicline plasma levels correlated with the higher doses of the drug.

However, "both diagnostic groups had lower plasma levels than expected in low dose and substantial variance within high dose varenicline," the investigators note.

Kozak pointed out the study was too small and too short in duration to detect any sign of adverse neuropsychiatric events.

Nevertheless, the US Food and Drug Administration recently removed the black box warning from varenicline labeling on the basis of results from the EAGLES study, which suggested that neither varenicline or bupropion was associated with an increase in neuropsychiatric adverse events compared to either the nicotine patch or placebo.

The EAGLES trial was a double-blind, randomized, placebo-controlled trial that enrolled smokers with and those without psychiatric disorders, including schizophrenia.

The investigators are now working toward testing a possible combination approach in which patients with schizophrenia receive both varenicline and some form of noninvasive brain stimulation to determine whether this might modify cognitive deficits in this patient population and simultaneously help them quit smoking.

The study was supported by a fellowship from the University of Toronto and grants from Pfizer and the Canadian Institutes of Health Research. The authors have disclosed no relevant financial relationships.

Schizophr Res. Published online March 10, 2017. Abstract

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