Abstract
To the Editor
Nicotine replacement therapy has been widely marketed as a safe form of treatment to aid smoking cessation (Mulligan et al., 1990). One such therapy is nicotine patches, which are readily available in chemists worldwide. Patches are prescribed to patients that cease smoking in hospital to prevent nicotine withdrawal. We would like to present an interesting case of mania induced by the use of nicotine patches.
A 35-year-old man with a past history of bipolar disorder was on an involuntary treatment order for 1 year, and prescribed risperidone 6 mg and sodium valproate 2000 mg daily. He improved with treatment and was discharged to a community mental health team, but disengaged with treatment and follow-up after his treatment order lapsed and remained stable in the community for 2 years before his recent manic episode.
He presented in June 2011 with a 2-week history of deterioration in his mental state with accompanying manic symptoms but no psychosis. There was no alcohol or illicit substance use history. His recent life course was unremarkable except for his health concerns related to his mitochondrial myopathy which was diagnosed when he was young. Clarification of possible triggers to his manic episode revealed a recent abrupt cessation of cigarette smoking after a 20-year history of nicotine dependence (40 cigarettes/day). He started transdermal nicotine patches of the maximum 21 mg strength the next day and used them 24 hours a day, changing them every morning.
Within 3 weeks of starting the nicotine patch, his energy levels increased and his sleep decreased to 3 hours overnight. He was noted by family to be irritable with uncontrollable anger and physical aggression towards property. At the time of admission, he had increased psychomotor activity, pressured speech, and an elevated mood.
All investigations conducted were normal but his MRI showed early onset generalized cerebral atrophy that was more than expected for his age.
He was started on low dose quetiapine (100 mg/day) as he was apprehensive about the potential side effects of an antipsychotic on his myopathy. Nicotine patches were ceased at the time of his admission to hospital. He improved within a week on quetiapine initiation and the cessation of nicotine patches. He was therefore discharged after a brief admission on 100 mg of quetiapine.
The temporal correlation between the onset of his manic symptoms and the use of nicotine patches continuously suggested a possible correlation between excessive nicotine levels and the precipitation of a manic episode. The quick resolution of his manic symptoms on a relatively low dose of quetiapine and with the cessation of nicotine patches supported this possible association. However, there is paucity of literature exploring this relationship (Benazzi, 1989; Labbate, 1992; Foulds and Toone, 1995; Foulds, 1996; Scurlock and Lucas, 1996).
There are two possible mechanisms by which the use of nicotine patches could have precipitated a manic episode. One possible explanation is a disruption of sleep/wake cycle induced by nicotine patches which acted as a stimulant (Foulds and Toone, 1995).
The other putative mechanism may involve the stimulation of mesolimbic dopaminergic cells mediated through cholinergic input via nicotinic receptors. Stimulation of nicotinic receptors by nicotine leads to a release of dopamine from mesolimbic neurons. Cigarette smoking is a pulsatile nicotine delivery system unlike transdermal skin patches that deliver nicotine continuously. In smokers, there is an upregulation of nicotinic cholinergic receptors over time to compensate for the fact that nicotine keeps turning the receptors off (Stahl, 1996). The use of nicotine transdermal patches in a reformed smoker can therefore lead to increased occupancy of nicotinic cholinergic receptors on mesolimbic dopaminergic neurons causing increased dopaminergic activity. In our patient having a vulnerable brain together with the fact he was not on maintenance mood stabilization treatment would have increased his vulnerability to a manic relapse under this potential hyperdopaminergic milieu.
The understanding of this potential risk is of clinical relevance given increased use of nicotine patches after the implementation of the non-smoking policy within health settings. This case report highlights the importance for clinicians to educate vulnerable patients about the proper use of nicotine patches and its potential stimulant and/or overdose effects especially with concurrent cigarette smoking. Based on this report and the limited literature covering this topic, we propose that this relationship be studied further in the future.