Robert Gibbons and John Mann published a meta-analysis of seventeen randomized, placebo-controlled studies involving 8,027 participants. They reported that varenicline (Chantix) improved tobacco abstinent rates when compared to placebo and buproprion (Wellbutrin). They also reported that valenicline was not associated with adverse psychiatric events, i.e., there was no greater incidence of depression, agitation, mood problems, or suicidal ideation in those treated with varenicline than those on placebo. The authors also evaluated a large data set from DOD involving 35,000 smokers. In this study in both the overall sample and the portion who had comorbid psychiatric diagnoses the smokers who received valenicline were awarded fewer diagnoses of psychiatric disorder than those who received nicotine replacement therapy. There is not evidence in these studies of new or emerging psychiatric symptoms.
In 2009 the U.S. Food and Drug Administration placed a black box warning for varenicline regarding adverse psychiatric events. This has placed clinicians in the unenviable position of proving a negative. i.e., psychiatric symptoms are not associated with the medication. The initial trials run by Pfizer, the manufacturer, to seek approval from the FDA excluded participants with a psychiatric diagnosis. After the drug was released and used in the community, depression, anxiety, mood disorders, and suicidal ideation and action were observed and the drug was blamed and the press sensationalized and inflated the adverse effects leading to caution on the part of prescribers. Had the initial trials not excluded those with a psychiatric diagnosis, then they could have been evaluated with a control group.
As a clinician I am always balancing the risks, continuing smoking, with the benefits, decreased mortality from many causes. The risk is high and the benefit is substantial. The data are clear. A large proportion of smokers who want to quit and use pharmacological cessation aids can quit and psychiatric symptoms remain relatively stable during and after quitting. I advise that any increase in anxiety, depression, irritability etc. are transient and mild. I do advise them to expect nausea and vivid dreams which I treat if troublesome.