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Pharmacist, Avera Behavioral Health Center, 4400 West 69th Street, Suite 1800, Sioux Falls, South Dakota 57108, fax 605/322-5917, anne.morstad{at}mckennan.org
Associate Professor of Pharmacy Practice, College of Pharmacy, South Dakota State University, Clinical Assistant Professor of Psychiatry, Sanford School of Medicine, University of South Dakota, Clinical Pharmacy Specialist, Psychiatry, Avera Behavioral Health Center, Sioux Falls, South Dakota
Clinical Associate Professor of Pharmacy, College of Pharmacy, University of Georgia, Savannah, Georgia
Assistant Professor, College of Pharmacy, University of Oklahoma, Department of Pharmacy: Clinical and Administrative Sciences, Tulsa, Oklahoma
Published Online, January 15, 2008. www.theannals.com, DOI 10.1345/aph.1K511
4β2 nicotinic receptor partial
agonist approved for smoking
cessation.1
We report a case of probable hypomania due to initiation of varenicline
therapy in a woman diagnosed with bipolar II disorder. Case Report. A 41-year-old white woman with a history of bipolar II disorder and polysubstance abuse presented to the hospital with irritability and suicidal ideation. She reported abstinence from alcohol for 3 months and from methamphetamine for 3 years. Her medications at the time of admission included bupropion XL 300 mg every morning, clonazepam 1 mg at bedtime, oxcarbazepine 150 mg every morning and 300 mg at bedtime, quetiapine 100 mg as needed for insomnia, montelukast 10 mg, and pantoprazole 40 mg every morning. With the exception of clonazepam, which had been started 5 months prior to her admission, she had taken these medications for more than a year. She was also taking varenicline 1 mg twice daily, started approximately 1 month prior. She smoked 2 packs of cigarettes per day and made several unsuccessful attempts to quit with nicotine replacement formulations and bupropion. The patient was otherwise healthy—all laboratory test results were within normal limits.
Using the recommended titration schedule, the woman had found that, within 2 days of starting varenicline, cigarettes had begun to taste unpleasant, and she decreased her amount of smoking. However, she also reported that, after 3 days of taking varenicline, she became irritable, her "skin crawled," and she felt "wacko." At that point, she decided to discontinue taking the drug. She reported that upon discontinuation of varenicline, those symptoms resolved.
A few days later, she developed a "head cold" which she treated with over-the-counter products, including vitamin C and Alka Seltzer Cold (which contains a decongestant and an antihistamine). When the cold reinforced her desire to quit smoking, she decided to restart varenicline. She became increasingly irritable and angry and was sleeping only about 2 hours a night. Her symptoms continued for several weeks, at which point she had a fight with her husband and made a suicidal gesture. She reported crying uncontrollably and feeling so tense that she felt that her "body was crawling"; she also scratched her arms and pulled clumps of hair from her head. At that point she was admitted to the hospital due to suicidal ideation, feelings of hopelessness and irritability, insomnia, agitation, and racing thoughts. Her psychiatrist, who had treated her for approximately 10 years, diagnosed a hypomanic episode with suicidal ideation. By the patient's own report, she had experienced a similar episode 10 years prior to this. Varenicline was discontinued; quetiapine dosing was changed to 25 mg 3 times per day as needed for agitation and 50 mg at bedtime for sleep; guanfacine 1 mg every night was added for explosive anger. Her symptoms improved greatly and she was discharged 3 days later.
Discussion. Alternatives to varenicline's being the cause of the patient's symptoms include (1) nonadherence to drug therapy (the patient asserted that she had been taking her medications as directed and nothing suggested otherwise), (2) illicit drug use (she reported abstinence from illicit drugs and alcohol; a urine drug screen was positive for cannabis, but she was discharged before the results were known and was unavailable to respond), and (3) nicotine withdrawal (the timing of the symptoms went beyond that expected if withdrawal were the culprit; nicotine withdrawal symptoms are generally short-lived and the patient's symptoms lasted at least a month).
The Naranjo criteria indicated a probable association of varenicline with this episode of hypomania.1 Psychiatric complaints such as insomnia (20.9-33.9%), irritability (21%), and abnormal dreams (11.6-19.4%) were reported as adverse events in clinical trials of varenicline, but those trials were conducted in nonpsychiatric populations.2,3 We identified one published case of a manic episode4 and another of an exacerbation of schizophrenia associated with varenicline.5 Recently, the Food and Drug Administration sent out a safety alert informing healthcare professionals of reports of suicidal thoughts and aggressive and erratic behavior in patients who have taken varenicline.6 With the widespread use of smoking cessation products in psychiatric populations, it is important that providers be made aware of the potential for psychiatric adverse effects with this medication.
References
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