An Emerging Positive Role for Nicotine in the Treatment of Depression

This discussion is about nicotine as a chemical, possibly delivered as a transdermalpatch, in chewing gum, nasal spray, or even inhaled. It is not about nicotine contained in tobacco which, when smoked or chewed, is extremely hazardous to a person’s health. Furthermore, the research about nicotine’s benefit is still under investigation and reasonably tentative. There are ongoing studies of nicotine’s possible usefulness in disease states as diverse as depression, schizophrenia, attention deficit disorder, Tourette’s syndrome, Alzheimer’s disease, Parkinson’s disease, and ulcerative colitis. Nicotine may also have a role in stimulating respiration and in pain relief. In this article I will take up nicotine’s role in depression.

My own interest in nicotine comes from many years of hearing a variety of psych-iatric patients report on the positive benefits of smoking cigarettes. Many individuals, with a variety of diagnoses, asserted that smoking helped their mood and/or ability to concentrate. During my first year of residency training at a public psychiatric hospital with many chronic patients, I wondered why the medium of exchange among patients was cigarettes, even partially smoked ones. Sometime later, when I declared my private office a smoke free environment, there was an outpouring of dismay from many patients telling me that they could not talk about serious emotional issues without the comfort of a lit cigarette. Several stopped treatment with me over the issue, even though I pointed out I was not insisting that they stop smoking, but only defending my own air quality (I have mild asthma). Therefore, the recent positive reports about nicotine intrigued me.

Here are the highlights of what I have learned, much of it from a new book entitled, Nicotine in Psychiatry: Psycho- pathology and Emerging Therapeutics (1).

Depression
In 1988, Glassman and colleagues found a surprisingly high prevalence (61%) of a past diagnosis of major depression in smokers recruited for a smoking cessation study. All the subjects were not depressed at the time of entry into the study. Nonetheless, those smokers with a past diagnosis of major depression had a significantly poorer outcome. Other researchers confirmed this finding linking major depression to smoking. For example, Covey et al, measured the frequency of major depression after smoking cessation in subjects who were not depressed at the time of quitting. Whereas 30% of subjects with a history of major depression got depressed in the 3 month period following smoking cessation, only 2% of subjects without a history of depression got depressed in that same time frame. Could patients prone to major depression be self-medicating with the nicotine derived from cigarette smoking? Researchers addressed this question, in part, by testing a variety of antidepressants for possible effectiveness in smoking cessation. Only a couple of antidepressants have been reported out positively, buproprion (Wellbutrin or Zyban) in many studies and nortryptilene in at least one study. Indeed, in 1997 Glaxo Wellcome obtained U. S. Food and Drug Administration approval for the use of the antidepressant buproprion-SR (sustained release) as a non-nicotine aid for use in smoking cessation. The really interesting finding is that buproprion-SR showed efficacy not only in depressed people trying to stop smoking, but also in individuals without any history of depression. Furthermore, buproprion is a rather unique antidepressant. Unlike most other antidepressants, buproprion affects the dopamine neurotransmitter system in the brain, a system well known as central to the brain’s reward and motivational systems. For example, dopamine brain levels rise precipitously in animals given any of a variety of addicting agents (opiates, alcohol, cocaine).

Other studies point out that the biological activity of nicotine is potent and complex and not necessarily dependent entirely on its effect on dopamine. Nicotine itself binds directly to cholinergic receptors in the peripheral and central nervous system, acting as an agonist. This cholinergic activity may be linked to the apparent cognitive-performance-enhancing properties of nicotine, insofar as the cholinergic system plays a key role in memory, attention, and related functions. (2) Thus, the role of nicotine in aiding depression sufferers may lie, in part, in the correction of the cognitive deficits which are an important part of the clinical picture one sees in major depression. Although many questions remain, some things are already clear: research studies in smoking cessation have to control for patients’ current and past histories of depression (as well as other psychiatric disorders). Likewise, studies of treatments for depression will have to control for smoking, given that many people modulate negative affects with nicotine. It is also likely that either nicotine or nicotine-like drugs will eventually be marketed for the treatment of depression, both in smokers and non-smokers. (3) Moreover, one should never forget that whatever the psychopharmacological benefits of nicotine, smoking as a behavioral disorder is deadly with 50% of users dying from a tobacco-related illness. Despite this, smoking is one of the least diagnosed disorders (less than half of physicians mention it in their patient care documentation) and one of the least reimbursed (less than 60% of health plans cover smoking cessation treatment). (4)

References

1. Piasecki M, Newhouse, PA editors: Nicotine in Psychiatry: psychopathology and emerging therapeutics American Psychiatric Press, Inc., Washington, DC,
   2000, 297 pages.
2. Ibid, P 118-119
3. Ibid, P 134-144
4. Ibid, P xiii (Foreword)