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A Review of the Effects of Nicotine on Schizophrenia and Antipsychotic Medications
Edward R. Lyon, M.S., Ed.D.
Psychiatric Services 1999; doi:
Abstract

OBJECTIVE: Research on the impact of nicotine on schizophrenia and antipsychotic medications was reviewed to determine ways to improve treatment planning for patients with schizophrenia who smoke and to evaluate smoking cessation programs for this population. METHODS: All major research databases were searched. The review focuses on reports published since 1990. RESULTS: 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. Use of traditional antipsychotics may result in patients' smoking more, whereas patients taking atypical antipsychotics may smoke less. Patients who smoke metabolize antipsychotics faster than nonsmoking patients. Smoking cessation programs for outpatients with schizophrenia report a success rate of about 12 percent after six months. No studies of cessation programs for chronically ill inpatients with schizophrenia have been published. Several hospitals have implemented smoking bans with equivocal results. CONCLUSIONS: Nicotine affects both schizophrenia and antipsychotic medications. Neurobiological and psychosocial factors reinforce the high use of nicotine by patients with schizophrenia

Abstract Teaser
Figures in this Article

Many patients in psychiatric hospitals would smoke two, three, or even four packs of cigarettes a day if an unlimited supply of cigarettes were available. However, most patients do not have an unlimited supply, mainly because of the cost. When patients smoke all of their cigarettes, some may resort to stealing, begging, prostitution, intimidation, and similar behaviors to obtain more.

During the past few years, considerable interest and research has been focused on the high use of cigarettes in psychiatric populations. Before the mid-1980s, most studies focused on depression and anxiety. Patients with major depression and anxiety are more likely to smoke than patients without these disorders, and they experience more problems when they attempt to quit smoking (1,2,3,4,5,6). Several other diagnostic groups have higher rates of nicotine use. They include patients with alcohol abuse and dependence, panic disorder, and personality and adjustment disorders (2).

Studies have consistently reported that patients with schizophrenia have the highest rate of nicotine use (2,7,8). Compared with other diagnostic groups, patients with schizophrenia are more likely to be heavy smokers, defined as those who smoke more than one and a half packs a day. Reports from hospitals suggest that chronically ill inpatients with schizophrenia have even higher rates of smoking than other patients with this disorder, and research supports this observation. For example, in a British study of 100 institutionalized patients, Masterson and O'Shea (9) found that 92 percent of the men and 82 percent of the women smoked.

In 1990 about a quarter of the general U.S. population were smokers—28 percent of men and 22 percent of women (10). The rate of smoking among inpatients with schizophrenia has been found to be between three and four times the rate in the general population. If the average patient with schizophrenia smokes one and a half packs of cigarettes each day, then each year in the United States this patient population smokes more than 10 billion packs of cigarettes, or about $20 billion worth of cigarettes (8).

Patients with schizophrenia are also more likely to smoke high-tar cigarettes. One study found that nearly 59 percent of patients with schizophrenia smoked high-tar cigarettes, compared with less than one percent of the general public (11). Patients with schizophrenia also have smoked for longer periods compared with other groups (12,13). Lohr and Flynn (8) point out that these patients prefer cigarettes high in nicotine and frequently smoke them down to the very end. This practice leaves cigarette burns and yellow stains on their fingers, a condition often observed at institutions with chronic psychiatric patients. Although allowing cigarettes to burn to the very end is sometimes attributed to patients' forgetfulness or to their psychotic state, another factor may be involved. The highest level of nicotine is found at the very end of the cigarette, and thus this behavior may be reinforcing (9).

Until recently the high rate of smoking among patients with schizophrenia was poorly understood. Current research suggests a link between nicotine, schizophrenia, and antipsychotic medication. This link has direct implications for treatment, as well as for the therapeutic milieu in psychiatric hospitals. This paper examines neurobiological and psychosocial factors that contribute to the high rate of smoking among patients with schizophrenia and describes the interaction of nicotine and antipsychotic medications. The effectiveness of smoking cessation programs is reviewed, and recommendations are made for improving treatment of patients with schizophrenia who smoke.

The keywords "nicotine," schizophrenia," and "antipsychotics" were used to search all major research databases. All studies located were examined, although not all are reviewed here. For example, several studies related to neuroleptic-induced movement disorders and nicotine were excluded to stay within the word limitations for publication. The review focuses on studies published since 1990.

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Neurobiology of nicotine and schizophrenia

Although several factors are involved in the high rate of smoking among patients with schizophrenia, the area of neurobiology is the most interesting. Neurobiological factors provide the strongest explanation for the link between smoking and schizophrenia because a direct neurochemical interaction can be demonstrated.

Nicotine is involved with several neurotransmitters, including glutamate, acetylcholine, serotonin, and norepinephrine, but its effects on dopamine are likely the most relevant in understanding the high use of nicotine by patients with schizophrenia (14,15). Research has shown that nicotine increases mesolimbicocorticol dopaminergic activity in the nucleus accumbens and the prefrontal cortex (16,17). This stimulation of dopamine could help explain the high use of nicotine as a form of self-medication to reduce negative symptoms (18).

Hypofrontality, a reduction in neuronal activity in the frontal and prefrontal section of the brain, is believed responsible for the negative symptoms of schizophrenia (19,20,21). These symptoms include social withdrawal, apathy, anhedonia, and lack of motivation. Dopamine release in the nucleus accumbens and the prefrontal areas is associated with several pleasurable and reinforcing activities, such as eating and sex, as well as the use of drugs such as cocaine and amphetamines (22). By increasing the release of dopamine, nicotine is believed to produce similar results for patients with schizophrenia. Research reports by Svensson and associates (20) and Grenhoff and colleagues (23) further suggest that this dopamine increase may partially and temporarily reverse symptoms of hypofrontality.

Although traditional antipsychotics appear to have a greater impact on positive symptoms than on negative symptoms (8), the newer agents have been shown to reduce negative symptoms (24,25,26). At least two of the newer antipsychotics have been shown to reduce nicotine use (27,28). These newer drugs are believed to be better than nicotine in reversing hypofrontality (23,25). Thus the atypicals may benefit patients by reducing both nicotine use and negative symptoms.

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Psychosocial aspects of nicotine and schizophrenia

Besides the neurobiological link between nicotine and schizophrenia, psychosocial factors are involved (29). People in the general population report that nicotine use induces relaxation and pleasurable feelings and reduces anxiety, anger, and depression. These effects may have greater importance among patients with a major mental illness because their sources of pleasure and satisfaction are likely diminished. Glynn and Sussman (30) found that most patients with schizophrenia felt more relaxed and less anxious after smoking. Reduction of the negative symptoms of schizophrenia, such as social and emotional withdrawal, through either psychosocial or neurochemical actions, might increase patients' interaction with others. Increased social contact may reduce feelings of isolation and thus reinforce nicotine use.

The depressive symptoms that are often experienced by patients with schizophrenia also influence the rate of smoking. Studies have shown that depression is associated with increased smoking, more difficulty withdrawing from nicotine, and a greater relapse rate after quitting (31,32).

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Interaction of nicotine and antipsychotics

No evidence links metabolism of medications directly to nicotine. However, polycyclic hydrocarbons in cigarette smoke stimulate the hepatic microsomal system, inducing liver enzymes to increase the metabolism of psychotropic medications (33). Nemeroff and colleagues (34) suggest that the induction of the cytochrome P450 1A2 isoform may explain the increased metabolism. The cytochrome P450 isoenzymes are involved in the oxidative metabolism of several different types of drugs including the majority of antidepressants and antipsychotics.

Several studies have reported that smokers require higher levels of antipsychotics than nonsmokers (7,31,35). Smoking can lower the blood levels of some antipsychotics by as much as 50 percent, requiring a corresponding increase in dosage to achieve therapeutic blood levels. For example, Ziedonis and associates (29) found that the average antipsychotic dosage for smokers in their sample was 590 mg in chlorpromazine equivalents compared with 375 mg for nonsmokers.

Other studies have investigated the connection between specific antipsychotics and the rate of smoking among patients with schizophrenia. McEvoy and colleagues (27) found that patients who started haloperidol treatment smoked more, as measured by their expired-air carbon monoxide and plasma nicotine and cotinine levels, than they did at baseline when they were free of antipsychotic medications. The same researchers studied smoking rates among patients switched from haloperidol to clozapine (36). Patients switched to clozapine at therapeutically effective dosages decreased their smoking, while those whose dosages were below therapeutic ranges showed no change in smoking behavior. George and associates (28) found a similar reduction in smoking when patients were placed on clozapine.

Albanese and coworkers (37) reported that patients with schizophrenia who were treated with clozapine showed a reduction in alcohol, cocaine, and heroin abuse. This finding is interesting because several of the atypicals—clozapine, risperidone, and olanzapine—may increase cortical dopamine release in a manner similar to that of nicotine (25,26). Besides clozapine, amperozide, another atypical antipsychotic, also has been reported to reduce negative symptoms of schizophrenia (19,23,24). This finding strengthens the position that the newer antipsychotics may reduce hypofrontality and thus reduce nicotine dependence among patients with schizophrenia.

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Effects of smoking on auditory physiology

Among persons who do not have schizophrenia, the auditory evoked response to the second of two paired auditory stimuli is significantly lower than the response to the first. Patients with schizophrenia have a deficit in this sensory gating function so that their response to the second stimulus is significantly greater than normal. This defect is one of several auditory sensory gating deficits in schizophrenia. Patients' impaired ability to filter out background noise in the environment would interfere with attention and with processing sensory stimuli.

Adler and associates (38,39) found that subjects with schizophrenia had a marked improvement in auditory gating immediately after smoking, whereas subjects without schizophrenia showed a slight impairment. This finding suggests that nicotine can temporarily normalize the impairment of auditory gating in subjects with schizophrenia.

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Smoking cessation programs and schizophrenia

Patients with schizophrenia not only smoke at high rates but are less likely to stop smoking than persons in the general population (31). One reason may be that patients with this disorder have less motivation to stop smoking (40). More research is needed to compare patients with schizophrenia with other patient groups to determine whether they have less motivation to quit and whether a larger proportion of patients with schizophrenia are unable to stop smoking.

Research on smoking cessation programs for patients with schizophrenia is limited. Ziedonis and George (33) conducted a ten-week smoking cessation program for 24 volunteer outpatients with schizophrenia. Patients continued to receive their usual psychiatric treatment. The average patient had smoked for 27 years and at the time of the study smoked about one and a half packs a day. At the end of six months, three patients remained smoke free with nicotine replacement.

Traditional smoking cessation treatment may not work for patients with schizophrenia because of their illness. Addington (41) described an eight-week smoking cessation program modified for patients with schizophrenia. To test this approach, 50 patients with schizophrenia participated in one of five smoking cessation groups. Forty-two percent were smoke free for four weeks, 16 percent stopped smoking for three months, and 12 percent were smoke free at six months.

Some research indicates that patients with schizophrenia may experience more problems when they attempt to quit smoking. Ziedonis and George (33) found that 71 percent of their sample of patients with schizophrenia reported substantial withdrawal symptoms, which resulted in a smoking relapse. These symptoms included craving, anxiety, concentration problems, irritability, increased appetite, and restlessness.

No studies have examined smoking cessation programs for chronic inpatients with schizophrenia. Because of the severity of psychosis in this patient group, it would be difficult to develop and promote such treatment approaches. These patients have marked affective, cognitive, and social disturbances that would make the educational approaches of traditional smoking cessation programs questionable. Clearly, the motivational and cognitive skills necessary to comprehend the need to reduce or eliminate the use of nicotine are compromised among chronic inpatients.

Several psychiatric hospitals have attempted a smoking ban, but the results are inconclusive. Velasco and associates (42) reported the effects of a ban on smoking on a 25-bed psychiatric inpatient unit. Immediately after the smoking ban and for two years, they found no increase in calls for security assistance, physical assaults, restraints, or seclusion. Verbal assaults and as-needed medications for anxiety increased immediately after the ban but were not a problem two years later.

Haller and colleagues (43) also found little impact on ward milieu after a complete smoking ban was initiated on a locked ward where the median length of stay was two weeks. Although staff anticipated problems before the ban, the majority voted to keep the ban after it was implemented. Patients' views were negative both before and after the ban.

Greeman and McClellan's study (44) found many problems with a smoking ban at a Veterans Affairs medical center. They reported that 20 to 25 percent of patients experienced significant problems, some of which caused major disruption to their treatment. The authors speculated that problems associated with smoke-free inpatient settings were underreported in the literature.

Nicotine and the polycyclic hydrocarbons in cigarettes have significant implications for patients with schizophrenia who take antipsychotic medications. Research studies cited here suggest that these chemicals may increase dopamine in the nucleus accumbens and the prefrontal cortex. Research further indicates that an increase in dopamine in these areas of the brain has an impact on hypofrontality, a condition believed to be related to the negative symptoms of schizophrenia. The use of nicotine also temporarily improves sensory gating among patients with schizophrenia, which may increase patients' ability to interact with their environment.

The interaction between nicotine and antipsychotic medications should be considered in clinical decisions. Among patients who smoke, typical antipsychotics are likely to increase smoking, whereas the atypical medications may decrease this behavior. Heavy smoking may decrease the blood levels of antipsychotic medications by as much as 50 percent.

Smoking cessation programs for outpatients with schizophrenia have resulted in small reductions in smoking. No reports of smoking cessation programs for chronic inpatients have been published, perhaps reflecting the difficulty of designing such programs for severely ill patients. Several hospitals have experimented with a smoking ban for staff and patients. The results are inconclusive. Some hospitals report few problems, but one research team speculated that problems related to smoking restrictions are underreported. More research on smoking bans is needed.

The following recommendations are based on the studies reviewed here.

• Clinicians conducting psychiatric evaluations of patients with schizophrenia should determine whether and how much patients smoke.

• Smoking alters the metabolism of psychotropic drugs, a factor that clinicians should consider when prescribing these medications.

• Patients with schizophrenia who are dependent on nicotine should not be denied smoking opportunities without being provided alternatives.

• To reduce the distress of patients who cannot monitor their use of cigarettes and thus use up their supply, treatment teams should consider monitoring the use of cigarettes by such patients.

• Patients who cannot obtain their own supply of cigarettes should be provided the means to acquire them so that they will not resort to prostitution, trafficking, assault, and similar disruptive behaviors.

• Although atypical antipsychotics may reduce smoking among patients with schizophrenia, other interventions, such as specialized smoking cessation programs, should be developed, especially for chronic inpatients.

Dr. Lyon is director of psychology at the G. Pierce Wood Memorial Hospital, 5847 Southeast Highway 31, Arcadia, Florida 34266-9627 (e-mail, edward_lyon@dcf.state.fl.us).

Glassman H: Cigarette smoking: implications for psychiatric illness. American Journal of Psychiatry 150:546-553,  1993
 
Hughes JR, Hatsukami DK, Mitchell JE, et al: Prevalence of smoking among psychiatric outpatients. American Journal of Psychiatry 143:993-997,  1986
 
Breslau N, Kilbey MM, Andreski P: Nicotine dependence and major depression: new evidence from a prospective investigation. Archives of General Psychiatry 50:31-35,  1993
 
Paulson GW: Addiction to nicotine is due to high intrinsic levels of dopamine. Medical Hypothesis 38:206-207,  1992
 
Anda RF, Williamson DR, Escobedo LG, et al: Depression and the dynamics of smoking: a national perspective. JAMA 264:1541-1545,  1990
 
Kendler KS, Neale MC, MacLean CL, et al: Smoking and major depression: a causal analysis. Archives of General Psychiatry 50:36-43,  1993
 
Goff DC, Henderson DC, Amico E: Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. American Journal of Psychiatry 149:1189-1194,  1992
 
Lohr JB, Flynn K: Smoking and schizophrenia. Schizophrenic Research 8:93-102,  1992
 
Masterson E, O'Shea B: Smoking and malignancy in schizophrenia. British Journal of Psychiatry 145:429-432,  1984
 
Dalack GW, Glassman AH: A clinical approach to help psychiatric patients with smoking cessation. Psychiatric Quarterly 63:27-39,  1992
 
O'Farrell TJ, Connors GJ, Upper D: Addictive behaviors among hospitalized schizophrenic patients. Addictive Behaviors 8:329-333,  1983
 
MacKenzie TD, Bartecchi CE, Schrier RW: The human costs of tobacco use, part 2. New England Journal of Medicine 330:975-980,  1994
 
Calabresi M, Casu G, Dalle Luche R: The prevalence of smoking in psychiatric patients: the effect of "institutionalization" [in Italian]. Minerva Psichiatrica 32:89-92,  1991
 
Wonnacott S, Draso A, Sanderson E, et al: Presynaptic nicotinic receptors and the modulation of transmitter release, in The Biology of Nicotine Dependence. Edited by Bock G. New York, Wiley, 1990
 
Vidal C: Nicotine potentiation of glutamatergic synapses in the prefrontal cortex: new insights into the analysis of the role of nicotinic receptors in cognitive functions. Drug Development Research 31:120-126,  1994
 
Corrigall WA: Understanding brain mechanisms in nicotine reinforcement. British Journal of Addictions 86:507-510,  1991
 
Lapin EP, Maker HS, Sershen H, et al: Action of nicotine on accumbens dopamine and attenuation with repeated administration. European Journal of Pharmacology 160:53-59,  1989
 
Dalack GW, Healy DJ, Meador-Woodruff JH: Nicotine dependence in schizophrenia: clinical phenomena and laboratory findings. American Journal of Psychiatry 155:1490-1501,  1998
 
Weinberger DR, Berman KF, Illowsky BP: Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia: III. a new cohort and evidence for a monoaminergic mechanism. Archives of General Psychiatry 45:609-615,  1988
 
Svensson TH, Grenhoff J, Enberg G: Effect of nicotine on dynamic function of brain catecholamine neurons, in The Biology of Nicotine Dependence. Edited by Bock G. New York, Wiley, 1990
 
Paulman RG, Devous, MD, Gregory RR, et al: Hypofrontality and cognitive impairment in schizophrenia: dynamic single-photon tomography and neuropsychological assessment of schizophrenia brain function. Biological Psychiatry 27:377-399,  1990
 
Pfaus JG, Damsma G, Nomikos GG, et al: Sexual behavior enhances central dopamine transmission in the male rat. Brain Research 530:345-348,  1990
 
Grenhoff TJ, Tung CS, Ugedo L, et al: Effects of amperozide, a putative antipsychotic drug, on rat midbrain dopamine neurons recorded in vivo. Pharmacology and Toxicology 66:29-33,  1990
 
Axelsson R, Nilsson A: Clinical effects and pharmacokinetic properties of amperozide. Psychopharmacology 104:287-292,  1991
 
Moghaddam B, Bunney BS: Acute effects of typical and atypical antipsychotic drugs on the release of dopamine from prefrontal cortex, nucleus accumbens, and striatum of the rat: an in vivo microdialysis study. Journal of Neurochemistry 54:1755-1760,  1990
 
Chouinard G, Jones B, Remington G, et al: A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. Journal of Clinical Psychopharmacology 13:25-40,  1993
 
McEvoy J, Freudenreich O, McGee M, et al: Clozapine decreases smoking in patients with chronic schizophrenia. Biological Psychiatry 37:550-552,  1995
 
George TP, Sernyak MJ, Ziedonis DM, et al: Effects of clozapine on smoking in schizophrenia outpatients. Journal of Clinical Psychiatry 56:344-346,  1995
 
Ziedonis DM, Kosten TR, Glazer WM, et al: Nicotine dependence and schizophrenia. Hospital and Community Psychiatry 45:204-206,  1994
 
Glynn SH, Sussman S: Why patients smoke (ltr). Hospital and Community Psychiatry 41:1027,  1990
 
Hughes JR: Possible effects of smoke-free inpatient units on psychiatric diagnosis and treatment. Journal of Clinical Psychiatry 54:109-114,  1993
 
Breslau N, Kilbey MM, Andreski P: Nicotine dependence, major depression, and anxiety in young adults. Archives of General Psychiatry 48:1069-1074,  1991
 
Ziedonis DM, George TP: Schizophrenia and nicotine use: report of a pilot smoking cessation program and review of neurobiological and clinical issues. Schizophrenia Bulletin 23:247-254,  1997
 
Nemeroff CB, DeVane CL, Pollock BG: Newer antidepressants and the cytochrome P450 system. American Journal of Psychiatry 153:311-320,  1996
 
Salokanga RK, Saarijarvi S, Taiminen T, et al: Effect of smoking on neuroleptics in schizophrenia. Schizophrenia Research 23:55-60,  1997
 
McEvoy J, Freudenreich O, Levin E, et at: Haloperidol increases smoking in patients with schizophrenia. Psychopharmacology 119:124-126,  1995
 
Albanese MJ, Khaantzian EJ, Murphy SL, et al: Decreased substance use in chronically psychotic patients treated with clozapine. American Journal of Psychiatry 151:780-781,  1994
 
Adler LE, Hoffer L, Wiser A, et al: Normalization of auditory physiology by cigarette smoking in schizophrenic patients. American Journal of Psychiatry 150:1856-1861,  1993
 
Adler LE, Olincy W, Waldo M, et al: Schizophrenia, sensory gating, and nicotinic receptors. Schizophrenia Bulletin 24:189-202,  1998
 
Hall RG, Suhamel M, McClanahan MG, et al: Level of functioning, severity of illness, and smoking status among chronic psychiatric patients. Journal of Nervous and Mental Disease 183:468-471,  1995
 
Addington J: Group treatment for smoking cessation among persons with schizophrenia. Psychiatric Services 49:925-928,  1998
 
Velasco J, Eells TD, Anderson R, et al: A two-year follow-up on the effects of a smoking ban in an inpatient psychiatric service. Psychiatric Services 47:869-871,  1996
 
Haller E, McNiel DE, Binder RL: Impact of a smoking ban on a locked psychiatric unit. Journal of Clinical Psychiatry 57:329-332,  1996
 
Greeman M, McClellan TA: Negative effects of a smoking ban on an inpatient psychiatry service. Hospital and Community Psychiatry 42:408-412,  1991
 
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References

Glassman H: Cigarette smoking: implications for psychiatric illness. American Journal of Psychiatry 150:546-553,  1993
 
Hughes JR, Hatsukami DK, Mitchell JE, et al: Prevalence of smoking among psychiatric outpatients. American Journal of Psychiatry 143:993-997,  1986
 
Breslau N, Kilbey MM, Andreski P: Nicotine dependence and major depression: new evidence from a prospective investigation. Archives of General Psychiatry 50:31-35,  1993
 
Paulson GW: Addiction to nicotine is due to high intrinsic levels of dopamine. Medical Hypothesis 38:206-207,  1992
 
Anda RF, Williamson DR, Escobedo LG, et al: Depression and the dynamics of smoking: a national perspective. JAMA 264:1541-1545,  1990
 
Kendler KS, Neale MC, MacLean CL, et al: Smoking and major depression: a causal analysis. Archives of General Psychiatry 50:36-43,  1993
 
Goff DC, Henderson DC, Amico E: Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. American Journal of Psychiatry 149:1189-1194,  1992
 
Lohr JB, Flynn K: Smoking and schizophrenia. Schizophrenic Research 8:93-102,  1992
 
Masterson E, O'Shea B: Smoking and malignancy in schizophrenia. British Journal of Psychiatry 145:429-432,  1984
 
Dalack GW, Glassman AH: A clinical approach to help psychiatric patients with smoking cessation. Psychiatric Quarterly 63:27-39,  1992
 
O'Farrell TJ, Connors GJ, Upper D: Addictive behaviors among hospitalized schizophrenic patients. Addictive Behaviors 8:329-333,  1983
 
MacKenzie TD, Bartecchi CE, Schrier RW: The human costs of tobacco use, part 2. New England Journal of Medicine 330:975-980,  1994
 
Calabresi M, Casu G, Dalle Luche R: The prevalence of smoking in psychiatric patients: the effect of "institutionalization" [in Italian]. Minerva Psichiatrica 32:89-92,  1991
 
Wonnacott S, Draso A, Sanderson E, et al: Presynaptic nicotinic receptors and the modulation of transmitter release, in The Biology of Nicotine Dependence. Edited by Bock G. New York, Wiley, 1990
 
Vidal C: Nicotine potentiation of glutamatergic synapses in the prefrontal cortex: new insights into the analysis of the role of nicotinic receptors in cognitive functions. Drug Development Research 31:120-126,  1994
 
Corrigall WA: Understanding brain mechanisms in nicotine reinforcement. British Journal of Addictions 86:507-510,  1991
 
Lapin EP, Maker HS, Sershen H, et al: Action of nicotine on accumbens dopamine and attenuation with repeated administration. European Journal of Pharmacology 160:53-59,  1989
 
Dalack GW, Healy DJ, Meador-Woodruff JH: Nicotine dependence in schizophrenia: clinical phenomena and laboratory findings. American Journal of Psychiatry 155:1490-1501,  1998
 
Weinberger DR, Berman KF, Illowsky BP: Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia: III. a new cohort and evidence for a monoaminergic mechanism. Archives of General Psychiatry 45:609-615,  1988
 
Svensson TH, Grenhoff J, Enberg G: Effect of nicotine on dynamic function of brain catecholamine neurons, in The Biology of Nicotine Dependence. Edited by Bock G. New York, Wiley, 1990
 
Paulman RG, Devous, MD, Gregory RR, et al: Hypofrontality and cognitive impairment in schizophrenia: dynamic single-photon tomography and neuropsychological assessment of schizophrenia brain function. Biological Psychiatry 27:377-399,  1990
 
Pfaus JG, Damsma G, Nomikos GG, et al: Sexual behavior enhances central dopamine transmission in the male rat. Brain Research 530:345-348,  1990
 
Grenhoff TJ, Tung CS, Ugedo L, et al: Effects of amperozide, a putative antipsychotic drug, on rat midbrain dopamine neurons recorded in vivo. Pharmacology and Toxicology 66:29-33,  1990
 
Axelsson R, Nilsson A: Clinical effects and pharmacokinetic properties of amperozide. Psychopharmacology 104:287-292,  1991
 
Moghaddam B, Bunney BS: Acute effects of typical and atypical antipsychotic drugs on the release of dopamine from prefrontal cortex, nucleus accumbens, and striatum of the rat: an in vivo microdialysis study. Journal of Neurochemistry 54:1755-1760,  1990
 
Chouinard G, Jones B, Remington G, et al: A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. Journal of Clinical Psychopharmacology 13:25-40,  1993
 
McEvoy J, Freudenreich O, McGee M, et al: Clozapine decreases smoking in patients with chronic schizophrenia. Biological Psychiatry 37:550-552,  1995
 
George TP, Sernyak MJ, Ziedonis DM, et al: Effects of clozapine on smoking in schizophrenia outpatients. Journal of Clinical Psychiatry 56:344-346,  1995
 
Ziedonis DM, Kosten TR, Glazer WM, et al: Nicotine dependence and schizophrenia. Hospital and Community Psychiatry 45:204-206,  1994
 
Glynn SH, Sussman S: Why patients smoke (ltr). Hospital and Community Psychiatry 41:1027,  1990
 
Hughes JR: Possible effects of smoke-free inpatient units on psychiatric diagnosis and treatment. Journal of Clinical Psychiatry 54:109-114,  1993
 
Breslau N, Kilbey MM, Andreski P: Nicotine dependence, major depression, and anxiety in young adults. Archives of General Psychiatry 48:1069-1074,  1991
 
Ziedonis DM, George TP: Schizophrenia and nicotine use: report of a pilot smoking cessation program and review of neurobiological and clinical issues. Schizophrenia Bulletin 23:247-254,  1997
 
Nemeroff CB, DeVane CL, Pollock BG: Newer antidepressants and the cytochrome P450 system. American Journal of Psychiatry 153:311-320,  1996
 
Salokanga RK, Saarijarvi S, Taiminen T, et al: Effect of smoking on neuroleptics in schizophrenia. Schizophrenia Research 23:55-60,  1997
 
McEvoy J, Freudenreich O, Levin E, et at: Haloperidol increases smoking in patients with schizophrenia. Psychopharmacology 119:124-126,  1995
 
Albanese MJ, Khaantzian EJ, Murphy SL, et al: Decreased substance use in chronically psychotic patients treated with clozapine. American Journal of Psychiatry 151:780-781,  1994
 
Adler LE, Hoffer L, Wiser A, et al: Normalization of auditory physiology by cigarette smoking in schizophrenic patients. American Journal of Psychiatry 150:1856-1861,  1993
 
Adler LE, Olincy W, Waldo M, et al: Schizophrenia, sensory gating, and nicotinic receptors. Schizophrenia Bulletin 24:189-202,  1998
 
Hall RG, Suhamel M, McClanahan MG, et al: Level of functioning, severity of illness, and smoking status among chronic psychiatric patients. Journal of Nervous and Mental Disease 183:468-471,  1995
 
Addington J: Group treatment for smoking cessation among persons with schizophrenia. Psychiatric Services 49:925-928,  1998
 
Velasco J, Eells TD, Anderson R, et al: A two-year follow-up on the effects of a smoking ban in an inpatient psychiatric service. Psychiatric Services 47:869-871,  1996
 
Haller E, McNiel DE, Binder RL: Impact of a smoking ban on a locked psychiatric unit. Journal of Clinical Psychiatry 57:329-332,  1996
 
Greeman M, McClellan TA: Negative effects of a smoking ban on an inpatient psychiatry service. Hospital and Community Psychiatry 42:408-412,  1991
 
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