Lifestyle issues
 
 
 
Schizophrenia and Tobacco
 
 
 
Introduction
 
Schizophrenia and tobacco use (and therefore nicotine dependence) are inextricably linked.  This relationship is poorly understood and has only recently been studied with any concerted effort.
 
 
Tobacco and Nicotine
 
Tobacco contains thousands of chemical substances, many of which are clearly harmful.  It could be said that tobacco is the package or the delivery system for nicotine.
 
 The May, 2005, issue of Harvard Health Letter indicated that “Most experts say nicotine itself does not cause cancer.”  Nicotine is the addictive component of tobacco products.  They went on to say “...it is the other substances in tobacco smoke (polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines) that cause DNA damage and therefore cancer.”
 
The tobacco industry did propose safer alternative mechanisms for nicotine delivery, but were faced with resistance from government agencies who maintained that these alternatives would constitute a means for the administration of a drug.  
 
Therefore they would be subject to the oversight and regulation of the FDA (Food and Drug Administration).  
 
Efforts to reduce exposure to the most hazardous elements of tobacco, for example by introducing better filters, only caused users to devise new strategies to obtain comparable doses of nicotine:  They took bigger drags, smoked cigarettes down to the filter (where they can obtain the highest levels of nicotine), or in the case of thinner or “light” varieties of cigarettes, smoked more of them.
 
Similar products that contain little or no nicotine are far less attractive to smokers.  It is clear that their aim is to acquire an adequate dose of nicotine.
 
A list of “Less Harmful Nicotine and Tobacco Products”, along with product descriptions, their relative risks, costs and sources, can be found at:  http://www.schizophrenia.com/smoke.htm
 
 
Nicotine
 
Nicotine is a remarkable substance that offers the user a number of attractive effects.  They report that it helps them concentrate, picks them up when they lack energy or feel down, but at the same time may produce a calming effect when they are stressed or anxious.
 
While other forms of tobacco have their own loyal followers, smokers find that they can most easily obtain their nicotine requirements.  Pipe smokers have access to high levels of nicotine due to concentrated smoke and the lack of filtration.  Chewing tobacco has been buffered to yield the optimal pH in the mouth to maximize the absorption of nicotine by the oral mucosa.  
 
Cigarette smokers are afforded the ideal conditions for the absorption of nicotine.  Not only are they able to absorb it from the lungs and oral mucosa, but they experience a direct and almost instantaneous stimulation of the vagus nerve when smoke enters the oral cavity.  In effect, they are “free-basing” nicotine.
 
 
Dependence
 
Nicotine, one of the many components of tobacco products, is addicting.  People who have used these products regularly, and then cease to use them, experience a withdrawal syndrome that is comprised of both physical and psychological symptoms.  
 
Physical signs of nicotine withdrawal include:  
 
  1. bradycardia (slower heart rate)
  2.  
  3. insomnia
  4.  
  5. gastointestinal discomfort
  6.  
  7. increased appetite (which may lead to weight gain).  
 
Psychological symptoms involve a negative affective state that can include:
 
  1. depressed mood
  2.  
  3. irritability or lower frustration tolerance
  4.  
  5. anxiety
  6.  
  7. poor concentration
  8.  
  9. craving
  10.  
  11. anhedonia (reduced interest, or a diminished or absent ability to experience pleasure).
 
 
Relationship to Schizophrenia
 
All of these psychological symptoms may also be present in people with Schizophrenia.  Anhedonia is sometimes reported by patients with depression.
 
Given that the vast majority of individuals who suffer from Schizophrenia smoke, it is difficult to make a determination about the precise origin of these symptoms (whether they are due to nicotine withdrawal, Schizophrenia, or both).
 
People who suffer from Schizophrenia may experience more intense symptoms of nicotine withdrawal.  This could be related to beneficial effects from nicotine that are not present in people who do not have this illness.
 
 
Incidence and Severity
 
Up to 90% of people with Schizophrenia smoke and show significant signs of nicotine dependence.1  This rate is more than three times that of the general population.  In addition to their high rate of smoking behavior, they are less likely to quit.  This could be due to reduced motivation or cognitive impairment as a consequence of their illness.
 
Patients with Schizophrenia show a greater frequency of tobacco smoking that patients with mood disorders.2
 
The severity of nicotine dependence is often measured by the FTND (Fagerstrom Test for Nicotine Dependence), a six item scale that determines the degree of dependence.  This measure may underestimate the degree of nicotine dependence in people suffering from Schizophrenia.1
 
There is ample evidence that the severity of nicotine dependence is unrivaled in patients suffering from Schizophrenia.  Most seasoned clinicians are familiar with patients in psychiatric hospitals who, before many institutions banned smoking completely, would smoke up to four packs of cigarettes per day if they had access to an unlimited supply.2  
 
Patients in those settings often turned to solicitation, stealing, threats or other forms of intimidation, prostitution and other drastic measures to obtain cigarettes when their access was limited or their supply exhausted.  Currently, the cost of tobacco products is often the principle limiting factor relative to the quantity used.
 
 
Treatment Complications
 
As a consequence of smoking bans, a new phenomenon has arisen that complicates the treatment of patients transitioning from inpatient settings to outpatient treatment.
Denying them access to tobacco products removes the interference with the metabolism of antipsychotic medications caused by smoking.  When patients are discharged and resume heavy smoking, they may encounter significant changes in the blood levels of their medications and a recurrence or exacerbation of symptoms.
 
 
Causes
 
Nicotine releases dopamine in the brain, which may in turn produce a number of desirable effects, including changes in mood, a reduction in negative symptoms, as well as attenuation of some of the side effects (movement disorders) of antipsychotic medications.
 
It has been proposed that people with Schizophrenia continue to seek out sources of nicotine (including tobacco, nicotine gum, etc.) to reduce the negative symptoms of Schizophrenia.  In some ways negative symptoms are similar to the symptoms of depression, and to some extent, the symptoms of nicotine withdrawal.  Before the advent of newer atypical antipsychotic agents, typical antipsychotics did little to improve negative symptoms or depressive symptoms.  In some cases they seemed to worsen negative symptoms.
 
Atypical antipsychotics appear to offer increased potential for improving negative symptoms, mood, and at least in the case of clozapine, a reduced risk for cognitive impairment.
 
Use of traditional (typical) antipsychotics may result in patients’ smoking more, whereas patients taking atypical antipsychotics may smoke less.2
 
Clozapine is the most effective treatment for negative symptoms and the only antipsychotic drug approved for the prevention of suicide in patients with Schizophrenia.  It also appears to decrease smoking.
 
Dalack and others3 offered clinical data to support the assertion that smoking in people with Schizophrenia may represent an attempt to self-medicate symptoms of the illness, particularly negative symptoms.
 
Nicotine may also serve as a coping mechanism, one that transiently reduces emotional and physical stress and promotes some degree of euphoria.
 
Nicotine appears to improve cognition in patients with Schizophrenia.
 
Ashwin Patkar, M.D., associate professor of psychiatry at Thomas Jefferson University in Philadelphia, completed a study described in the September, 2002, issue of the Journal of Nervous and Mental Disease.  This study indicated that people with Schizophrenia may also smoke to lessen poor attention, disorientation, unusual thought content, and poor impulse control.
 
This study also found an association between smoking and a longer duration of illness and a greater number of hospitalizations, even though the patients studied tended to be younger, suggesting that the severity of their illness may be a risk factor for smoking.
 
Smokers also reported more days of alcohol use in the month prior to hospital admission than nonsmokers.  It was postulated that alcohol might be a risk factor for smoking in people with Schizophrenia.
 
This association might also reflect the reverse, that smoking is a risk factor for alcohol use.
 
One study4 provided data that did not generally support the self-medication hypothesis, but rather suggested a complex interaction between nicotine dependence and the symptoms of Schizophrenia.  High PANSS (Positive and Negative Syndrome Scale) total scores and positive symptom scores were less frequent in mildly dependent smokers than in non-smokers or highly dependent smokers.  Highly dependent smokers had the worst outcome.
 
 
Mechanism
 
It has been proposed that nicotine withdrawal involves changes in several neurotransmitter systems, including the glutaminergic (glutamate), dopaminergic (dopamine), noradrenergic (norepinephrine), serotonergic (serotonin) and cholinergic (acetylcholine) systems.
 
Current thinking places more emphasis on the dopaminergic and cholinergic systems.
 
Ricardo Miledi, from the University of California, Irvine, discussing a pending study related to Nicotine Dependence5 noted that:
 
“Schizophrenics are chronic smokers:  between five to nine out of ten schizophrenics are addicted to tobacco.  Both disorders, Schizophrenia and tobacco addiction, are somewhat related to the nicotinic receptor, a protein involved in the communication between brain cells.  Interestingly, new drugs designed to fight schizophrenia, called “atypical neuroleptics”, reduce nicotine addiction among schizophrenics.”
 
Unfortunately, we do not know precisely how these medications work.
 
 
Neurobiology
 
Nicotine increases the activity of dopamine in several areas of the brain, including the frontal and prefrontal cortex.  Reduced dopamine activity in those regions is thought to produce negative symptoms.  Pleasure, including that related to sex, eating, and potent drugs that produce euphoria (cocaine and amphetamines) appears to be mediated by dopamine.  Nicotine may approximate these same effects.
 
The alpha 7 nicotinic cholinergic receptor, crucial for attention and thinking and faulty in the brains of schizophrenic patients, appears to be activated by nicotine.6
 
Smoking improves processing of auditory stimuli (sensory gating) by patients with Schizophrenia and may lessen negative symptoms by increasing dopamine in the nucleus accumbens and the prefrontal and frontal cortex.7
 
 
Psychosocial Factors
 
Many people who use nicotine in its various forms report calming, mild euphoria, and even an elevated mood with the use of nicotine.  These same effects are probably experienced by people with Schizophrenia.  These pleasurable sensations may assume greater importance due to a relative lack of opportunities for pleasure in people with Schizophrenia.  Relaxation achieved from the use of nicotine may facilitate socialization.
 
 
Consequences
 
Patients who smoke metabolize antipsychotics faster than nonsmoking patients.7  This does not appear to be related to nicotine, but rather to enzyme induction.  The production of liver enzymes is stimulated by other components of smoke.  Some of these enzymes are responsible for the breakdown of antipsychotic medication.  Higher levels of the enzymes result in a reduction in the levels of some antipsychotic medications.
 
Smokers with mental illness experience a substantial increase in the rates of heart disease, respiratory disorders and a variety of other health problems.
 
 
Financial Burden
 
Americans with Schizophrenia spend $20 billion dollars on cigarettes annually.6,9
 
 
Treatment
 
Intensive treatment programs aimed at reducing or eliminating smoking in patients with Schizophrenia claimed early success.  Smoking cessation programs for outpatients with Schizophrenia report a success rate of about 12% after six months.7
 
 
Summary
 
  1. Tobacco use and nicotine dependence affect people with Schizophrenia disproportionately, with rates much higher than the general population8 and higher than those seen with any other psychiatric disorder.
  2.  
  3. Patients with Schizophrenia are more likely to smoke high-tar cigarettes.10
  4.  
  5. They are more likely to have smoked longer.11,12
  6.  
  7. The reasons for these discrepancies may be related to their symptoms and the effects of nicotine on those symptoms.
  8.  
  9. Despite higher rates of heavy use, they are subject to the same negative consequences related to the use of tobacco products as other smokers.
  10.  
  11. Several factors, including those related to neurobiology and psychosocial factors, may be responsible for the high rate of smoking in people with Schizophrenia.
  12.  
  13. Typical antipsychotics may increase smoking; at least some of the atypicals have been shown to reduce this behavior.  The choice of medication could play an important role in assisting patients in their efforts to stop smoking, but success will likely require the cumulative benefit of several interventions.
  14.  
  15. Smoking affects the metabolism of antipsychotic medications and may represent a factor that complicates treatment, particularly when patients make a transition from a smoke free environment to one with lesser or no restrictions related to smoking.
  16.  
  17. Programs that limit or deny patients access to nicotine in some form may be contributing to a worsening of some of these patients’ symptoms and increased stress.
  18.  
  19. All available treatment modalities for smoking cessation have some rate of success.  None should be avoided or discouraged.
  20.  
  21. Conventional smoking cessation programs must be modified to meet the unique needs of people who suffer from Schizophrenia.
  22.  
  23. Research aimed at a more complete understanding of the causes for the high incidence of nicotine dependence in patients with Schizophrenia and the development of effective treatment modalities may be the most important single intervention we can offer patients with this disease.
 
 
Recommendations
 
  1. All healthcare, or allied professionals, involved with patients with Schizophrenia should remain aware of their clients’ use of tobacco products.
  2.  
  3. This knowledge should prompt these professionals to intervene through direct referrals for treatment, or at the very least, to regularly encourage clients to monitor their smoking, attempt to reduce consumption, or consider some type of intervention.
  4.  
  5. Identifying and critically analyzing patients with Schizophrenia who do not smoke may provide some clues to important factors that influence risk and have so far been overlooked.
 
 
1Steinberg ML, Williams JM, Steinberg HR, Krejcl JA, Ziedonis DM:  Applicability of the Fagerstrom Test for Nicotine Dependence in Smokers with Schizophrenia.  Addictive Behaviors 2005, vol. 30, No. 1, pp. 49-59
 
2de Leon, J, Diaz, FJ, Rogers, T, Browne, D, Dinsmore, L.  Initiation of daily smoking and nicotine dependence in schizophrenia and mood disorders. Schizophrenia Research, Volume 56, Issue 1-2, pp. 47-54 (July 2002)
 
3Dalack, GW, Healy, DJ, and Meador-Woodruff, JH.  Nicotine Dependence in Schizophrenia:  Clinical Phenomena and Laboratory Findings  Am J. Psychiatry  155:1490-1501, November 1998
 
4Aguilar, MC, Gurpegui, M, Diaz, FJ. De Leon, J.  Nicotine dependence and symptoms in schizophrenia:  Naturalistic study of complex interactions.  British Journal of Psychiatry  2005, March, Vol. 186, pp. 215-221
 
5from the TRDRP (Tobacco-Related Disease Research Program)
 
6Arehart-Treichel, J.  Symptom Relief May Keep Schizophrenia Patients Smoking.  Psychiatric News December 20, 2002, Volume 37, Number 24, p. 22
 
7Lyons, ER.  A Review of the Effects of Nicotine on Schizophrenia and Antipsychotic Medications  Psychiatr Serv 50:1346-1350, October 1999
 
8Dalack GW, Glassman AH:  A clinical approach to help psychiatric patients with smoking cessation. Psychiatric Quarterly 63:27-39, 1992
 
9Lohr JB, Flynn K:  Smoking and schizophrenia. Schizophrenia Research 8:93-102, 1992
 
10O’Farrrel TJ, Connors GJ, Upper D:  Addictive behaviors among hospitalized schizophrenic patients.  Addictive Behaviors 8:329-333, 1983
 
11MacKenzie TD, Bartecchi CE, Schrier RW:  The human costs of tobacco use, part 2. New England Journal of Medicine 330:975-980, 1994
 
12Calabresi M, Casu G, Dalle Luche R:  The prevalence of smoking in psychiatric patients:  the effect of “institutionalization”. Minerva Psichiatrica 32:89-92, 1991
 
 
(Sources:  The author’s knowledge base, unless otherwise noted.)
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Suicide
 
Lifestyle Issues
 
Schizophrenia and Alcohol Abuse or Dependence
 
Cognitive Impairment
 
Environment
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