Varenicline-Induced Manic Episode in a Patient With Bipolar Disorder

Abstract

TO THE EDITOR: Schizophrenia is associated with heavy smoking. The replacement of tobacco by other forms of nicotine only occasionally achieves abstinence in persons with schizophrenia (1). The nicotinic agonist varenicline is a new alternative replacement agonist. There are no reports of its use in schizophrenia. We present the case of a patient with schizophrenia who received varenicline and experienced an activated psychotic relapse.A 42-year-old woman with schizophrenia had been treated for 17 years with 1015 mg of thiothixene. She had several brief psychotic episodes per year, which seldom lasted for more than 3 days. She had no overt psychotic symptoms during an office visit one month previously. Her usual symptoms during acute psychotic episodes were voices commenting on her behavior, confusion, and angry outbursts. She smoked one to two packs of cigarettes per day and had made several attempts to discontinue the use of nicotine chewing gum and trandermal nicotine patches. The patient's mother reported a 5-day psychotic episode that began with increased activity, primarily the discarding of financial statements. At day 4, the patient ordered her daughter out of the house, and she threw away her thiothixene, which her daughter had insisted that she continue to take. She spent the next day screaming in her closet. Her mother administered thiothixene (20 mg) on the fifth evening and fed her because she had stopped eating. She appeared well groomed the next morning, without psychotic symptoms. She had no explanation for her sudden relapse and remission, but she announced with pride that her internist had prescribed a new medication, varenicline (2 mg), to help her stop smoking. The patient had been receiving varenicline for 5 days, and her quit day was the following day. She was advised to continue thiothixene, to avoid varenicline, and to return to nicotine chewing gum as a smoking substitute. She had no further exacerbations, but she continued to smoke cigarettes.Nicotine activates several classes of brain cholinergic receptors. Many are high affinity presynaptic receptors, composed primarily of alpha4 and beta2 subunits, which cause the release of dopamine and other neurotransmitters. Nicotine produces profound tachyphylaxis at doses that are close to its agonist effect, which quickly ends its pleasurable effect. Heavy smokers, including persons with schizophrenia, respond by increasing their smoking to overcome the tachyphylaxis. Varenicline is principally an agonist at high affinity receptors, with a lower propensity to tachyphylaxis than nicotine (2). The more prolonged agonist effect of the drug was selected to increase its acceptance by smokers as a substitute for the briefer effects of cigarettes. Prolonged release of dopamine and norepinephrine may have resulted in the activated psychotic relapse in our patient. Her relatively low neuroleptic dose likely increased her vulnerability to this effect.In addition to its pleasurable effects, smoking is a possible self-medication for cognitive dysfunction i...

Confronting a Neglected Epidemic: Tobacco Cessation for Persons with Mental Illnesses and Substance Abuse Problems

“…Even though patients with mental illnesses were excluded from these trials, there is anecdotal evidence that varenicline is being used in many such patients. Because of reports of suicidal ideation and worsening psychiatric symptoms in some patients using varenicline, the FDA issued a special alert and required Pfizer to provide a warning www.annualreviews.org • Confronting a Neglected Epidemicand a label change for varenicline (34,52,63,108). The FAA banned airline pilots from using varenicline (52).…”

Arrêter de fumer peut tuer !

“…En effet, plusieurs rapports portants sur des épisodes obsessionnels et sur une exacerbation de la schizophrénie induits par la varénicline ont été publiés dans la littérature [7][8][9][10]. Le 17 décembre 2007, l'agence européenne du médicament a dé-livré un communiqué de presse dans lequel elle concluait que des alertes sur l'induction potentielle d'idées suicidaires par la varénicline devraient être mises en place pour prévenir méde-cins et patients (www.afssaps.fr).…”

“…Il a été publié que la varénicline peut être associée à des troubles psychiatriques, en particulier chez des patients pré-sentant des désordres mentaux [7][8][9][10]. Dans ces cas là, l'utilisation de cette molécule n'est pas recommandée.…”

Varenicline: a new pharmacotherapy for smoking cessation in primary care practice

“…31 There have also been reports of activated psychotic relapse in schizophrenia, hypomania with agitation in a bipolar II disorder, and induction of a manic episode in a bipolar patient. 26,32 Also published was a case of a person who shot his neighbour while in a state of delirium caused by taking varenicline with a high dose of alcohol, though it was unclear whether the episode was related to the drug or to a state of alcoholic intoxication. Other post-marketing reports included agitation and depression.…”

“…Varenicline has also been linked to neuronal α7 nAChR1, which is linked to major psychiatric disorders. 26,32 Thus, when prescribing varenicline to mental health patients, primary care doctors need to consider the beneficial and adverse effects of varenicline. Prior to prescribing varenicline, it is thus important to establish the presence of mental health problems.…”