Response to Anandarajan et al.: Manic exacerbation induced by nicotine patch

To the Editor

In their letter to you, Anandarajan et al. (2012) purport that the daily use of a single 21 mg 24-hour nicotine patch for a 3-week period induced a manic episode in a 35-year-old man with a past history of bipolar disorder (BPAD). Anandarajan et al. (2012) suggest two possible explanations to account for their observation. The first relates to a disruption of the sleep/wake cycle induced by nicotine patches acting as a stimulant. The second proposed mechanism suggests that the patches stimulated nicotinic cholinergic receptors on mesolimbic dopaminergic neurons resulting in increased dopaminergic activity, and that this patient was particularly susceptible to this hyperdopaminergic activity due to “a vulnerable brain” and not being on maintenance mood stabiliser treatment. We believe that this association between the use of nicotine patches and manic relapse is largely unfounded, and is in fact a dangerous claim to make. To suggest that the very treatment which has the potential of saving the lives of many smokers that experience mental illness is doing harm is inaccurate and paternalistic.

Nicotine replacement therapy (NRT) first became available in the 1980s and since then millions of smokers worldwide have used some form of NRT during a smoking cessation attempt, with the majority purchasing these products over the counter (i.e. without a prescription) (Ferguson et al., 2011). There is well-substantiated evidence that all forms of NRT are safe, well tolerated and effective in quitting smoking (Ferguson et al., 2011). Anandarajan et al. (2012) are correct in saying that there is a paucity of literature exploring the relationship between ‘excessive’ nicotine levels and the precipitation of a manic episode. To the best of our knowledge, there has been no reported evidence that use of nicotine patches, or other forms of NRT generally, results in the experience of a manic episode. Our own work and that of others, among thousands of people experiencing psychosis, including hundreds with BPAD, demonstrates that people experiencing severe mental illness do not experience deterioration in their mental state, either in the form of a relapse to psychosis, depression or mania during smoking cessation, including those using NRT (Baker et al., 2006, 2009, 2011; Banham and Gilbody, 2010; Williams et al., 2011). However, smokers with a previous history of depression may experience a recurrence of depression during a quit attempt (Hughes, 2007), and this is more likely for those who experience protracted nicotine withdrawal symptoms. Nicotine withdrawal symptoms such as cravings, irritability, anxiety, restlessness, sleep disturbance, difficulty concentrating and lowered mood can act as stressors for people experiencing mental illness, in turn triggering or exacerbating other symptoms of mental illness (Fagerstrom and Aubin, 2009).

We propose that the manic episode may have been triggered by nicotine withdrawal symptoms experienced by this heavy smoker as a consequence of being underdosed with NRT. Contrary to the claims of Anandarajan et al. (2012), this patient would not have had excessive nicotine levels. The dose of nicotine delivered by the transdermal patch, and the speed at which the nicotine is delivered, is substantially lower than that achieved by smoking cigarettes (Sweeney et al., 2001), which disputes the claim made by Anandarajan et al. (2012) that the nicotine patches caused hyperdopaminergic activity. Furthermore, if this was in fact the case, we would expect to see the emergence of symptoms of psychosis, particularly in a patient such as the one described, who had previously required 6 mg of risperidone to remain asymptomatic. People with severe mental illness typically smoke heavily (> 20 cigarettes per day) and have high levels of nicotine dependence, and it has been recommended that combinations of NRT such as the nicotine patch, together with titratable forms of NRT (e.g. gum, lozenges) be used in this population (Hughes et al., 1999; Williams and Foulds, 2007). If this patient was referred to our Healthy Lifestyles Project for smoking cessation (Baker et al., 2011), we would recommend that he commence using 2 × 21 mg nicotine patches daily together with up to 12 × 2 mg nicotine lozenges, and the NRT would be titrated down over an extended period of time.

Finally we are very concerned that linking the use of NRT and smoking cessation to a manic relapse will frighten clinicians and give them yet another reason why people with mental illness should not quit smoking. The leading cause of premature death and morbidity in people with mental illness is cardiovascular disease, and smoking is the most significant contributing risk factor in this population (Colton and Manderscheid, 2006). We must take a common sense approach and remind ourselves that the use of nicotine through NRT products is far safer than smoking in and of itself. All smokers with mental illness should be advised, encouraged and supported to quit smoking as a matter of priority, and this should be done under the supervision of their treating team to ensure that nicotine withdrawal symptoms, mental illness symptoms and medication side effects are closely monitored.