BMC Proceedings volume 9, Article number: A31 (2015)
Varenicline is currently the most effective smoking cessation medication. Pre-marketing clinical trials excluded participants with psychiatric disorders, such as major depressive disorders. This study investigated the psychiatric effects of varenicline among patients with depression.
On 18 December 2012, a systematic search was performed using Medline with the following search terms: 1) varenicline and 2) depression. The search was limited to English articles, case reports, and original clinical studies. From the 58 retrieved documents, 15 articles were used in this review.
The first case report on the effects of varenicline on patients with depression was published in June 2008. A man experienced an acute exacerbation of depressive symptoms, which resolved after he stopped his varenicline treatment. [1] Since then, there were 8 other case reports that described exacerbation of psychiatric symptoms in patients with depression taking varenicline [2–9]. Two of those case studies suggested the use of sertraline [7] and bupropion [8] to treat exacerbation of depressive symptoms associated with varenicline. In contrast, varenicline was shown to improve the affective symptoms of a smoker who developed depression and suicidal tendencies during previous cessation attempts [10]. There were 3 observational studies on patients with depression taking varenicline: 1) a one-year follow-up study on 112 smokers showed an association between increased Beck Depression Inventory score and continued smoking after 12 weeks of varenicline [11]; 2) an open-labelled study showed significant improvement in mood in 110 outpatient smokers with persistent depressive symptoms [12]; and 3) A smoking cessation trial on 217 varenicline users showed that depressive symptoms at the time of varenicline initiation (measured by Patient Health Questionnaire-2) were associated with suicidal ideation. [13] There were 2 clinical trials on patients with depression taking varenicline, with both of them showing worsening of psychiatric symptoms. [14, 15] Neither of the trials were placebo-controlled.
Despite some inconsistencies, the findings suggested that varenicline could worsen psychiatric symptoms in patients with depression. Clinicians should be advised to closely monitor patients with a history of depression on varenicline, although there were no studies on how to treat those patients. Bias and uncontrolled confounders potentially affected previous studies, and thus, a double-blinded placebo-controlled trial is needed to demonstrate the efficacy and side effects of varenicline on patients with depression.
Popkin MK: Exacerbation of recurrent depression as a result of treatment with varenicline. Am J Psychiatry. 2008, 165: 774-
Pumariega AJ, Nelson R, Rotenberg L: Varenicline-induced mixed mood and psychotic episode in a patient with a past history of depression. CNS Spectr. 2008, 13: 511-514.
Pirmoradi P, Roshan S, Nadeem SS: Neuropsychiatric disturbance after initiation of varenicline in a patient with a history of alcohol abuse and major depression. Am J Health Syst Pharm. 2008, 65: 1624-1626.
Lyon GJ: Possible varenicline-induced paranoia and irritability in a patient with major depressive disorder, borderline personality disorder, and methamphetamine abuse in remission. J Clin Psychopharmacol. 2008, 28: 720-721.
Raidoo BM, Kutscher EC: Visual hallucinations associated with varenicline: a case report. J Med Case Rep. 2009, 3: 7560-1947-3-7560
Cantrell M, Argo T, Haak L, et al: Adverse neuropsychiatric events associated with varenicline use in veterans: a case series. Issues Ment Health Nurs. 2012, 33: 665-669.
Baran XY, Docherty JP: Rapid and sustained response to a single dose of sertraline in a patient with newly emergent depression during varenicline-assisted smoking cessation. CNS Spectr. 2010, 15: 148-151.
Karam-Hage M, Shah KR, Cinciripini PM: Addition of bupropion SR to varenicline alleviated depression and suicidal ideation: a case report. Prim Care Companion J Clin Psychiatry. 2010, 12: 10.4088/PCC.09l00800blu
Hussain S, Kayne E, Guwanardane N, et al: Varenicline induced mania in a 51 year old patient without history of bipolar illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011, 35: 1162-1163.
Grosshans M, Mutschler J, Hermann D, et al: Reduced affective symptoms during tobacco dependence treatment with varenicline. Addiction. 2009, 104: 859-861.
Grassi MC, Enea D, Ferketich AK, et al: Effectiveness of varenicline for smoking cessation: a 1-year follow-up study. J Subst Abuse Treat. 2011, 41: 64-70.
Philip NS, Carpenter LL, Tyrka AR, et al: Varenicline augmentation in depressed smokers: an 8-week, open-label study. J Clin Psychiatry. 2009, 70: 1026-1031.
Cowan CM, Wink JS, DeZee KJ: Use of the Patient Health Questionnaire-2 to predict suicidal ideations in patients taking varenicline. Am J Addict. 2012, 21: 356-362.
McClure JB, Swan GE, Jack L, et al: Mood, side-effects and smoking outcomes among persons with and without probable lifetime depression taking varenicline. J Gen Intern Med. 2009, 24: 563-569.
McClure JB, Swan GE, Catz SL, et al: Smoking outcome by psychiatric history after behavioral and varenicline treatment. J Subst Abuse Treat. 2010, 38: 394-402.
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Yeung, E., Long, S., Bachi, B. et al. The psychiatric effects of varenicline on patients with depression. BMC Proc 9 (Suppl 1), A31 (2015). https://doi.org/10.1186/1753-6561-9-S1-A31
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DOI: https://doi.org/10.1186/1753-6561-9-S1-A31
