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Letter to the Editor

Varenicline for Smoking Cessation in the Bipolar Patient

Ian R. Tofler, MBBS

Published: May 27, 2015

See reply by Chengappa et al and article by Chengappa et al

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Varenicline for Smoking Cessation in the Bipolar Patient

To the Editor: I commend Chengappa and coauthors for their recent NIMH-funded, non-industry supported article1 revisiting the use of the selective α4β2 nicotinic acetycholine receptor partial agonist varenicline in patients with bipolar disorder. The accompanying thoughtful commentary by Goldberg2 is similarly appreciated.

The Food and Drug Administration (FDA) does appear to hand out apparently damning black box warnings with alacrity, witness the citalopram and zolpidem edicts. These can be counterbalanced by strong research.3 But in the case of varenicline, the FDA warning is, in my opinion, fully justified.

Chengappa et al wisely used only euthymic bipolar disorder patients in their research, versus unstable bipolar patients. How they chose or defined this cohort is uncertain, as is whether comorbid substance abuse was screened out. The authors have helpfully presented useful information (albeit with a limited number of subjects) suggesting reasons for the high-risk nature of varenicline in psychiatric patients who are attempting smoking cessation. These include:

  1. Insomnia (45.2% vs 27.6% placebo)—confirmed by other industry-supported research (reference 4 and the March 9, 2015, FDA Safety Announcement), albeit in much lower numbers

  2. Abnormal dreams (58.0% vs 31.0% placebo)

  3. Suicidal ideation (6.5% vs 3.4%, 1 case with placebo)—a nonsignificant difference, (but 96.8% of their patients already had experienced pretreatment suicidal ideation, in other words a universal high-risk group for potential suicidality)

  4. Depressed mood (25.8% vs 6.9% placebo)

Brief case presentation. Ms A was a 32-year-old woman with chronic unstable bipolar I disorder with psychotic features (DSM-IV-TR) and polysubstance abuse including chronic nicotine dependence, which was partially controlled on medication. She had been requesting varenicline—after seeing advertising on television—for several years, which had been frequently denied by the psychiatrist. After starting with a busy new internist, she again requested a varenicline trial, which was granted. Within 3 days, she had completed a tragic suicide. There were no other overt precipitants to the suicide other than the varenicline trial.

In patients with unstable bipolar disorder, and especially those with psychotic features or comorbid substance abuse, any acute increase in insomnia could push them into an acute manic episode or aggravate comorbid symptomatology including psychosis and impulsive suicidality. It is also possible that varenicline may have a unique proimpulsivity, prosuicidality, or deliriogenic action.

The authors, supported by Goldberg’s commentary,2 state that the use of varenicline (and varenicline with bupropion) in the bipolar group should be implemented “in this highly vulnerable patient population.”1(p771) Goldberg states that varenicline is “a relatively simple intervention that could meaningfully help save our patients’ lives.”2(p774) They both attempt to whitewash and minimize a potentially problematic intervention.

In conclusion, while supporting the public health sentiments that all smoking cessation interventions should be strongly encouraged in this population, I would provide a major caveat that in the bipolar population, if indicated, varenicline should be commenced inpatient with monitored supervision for at least a week, so that discontinuation can be instituted immediately in a structured setting. Internists should refer these patients first to a psychiatrist as the implications and potential risks are high.


1. Chengappa KN, Perkins KA, Brar JS, et al. Varenicline for smoking cessation in bipolar disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014;75(7):765-772. PubMed doi:10.4088/JCP.13m08756

2. Goldberg JF. Efficacy of varenicline for smoking cessation in bipolar disorder. J Clin Psychiatry. 2014;75(7):773-774. PubMed doi:10.4088/JCP.14com09103

3. Zivin K, Pfeiffer PN, Bohnert AS, et al. Evaluation of the FDA warning against prescribing citalopram at doses exceeding 40 mg. Am J Psychiatry. 2013;170(6):642-650. PubMed doi:10.1176/appi.ajp.2013.12030408

4. Physicians’ Desk Reference. Montvale, NJ: PDR Network; 2014: 2420.

Ian R. Tofler, MBBS

Author affiliations: Department of Psychiatry, Kaiser Permanente, and Department of Psychiatry Clinical Faculty, University of California, Los Angeles, California.

Potential conflicts of interest: None reported.

Funding/support: None reported.

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