Smoking and substance abuse in outpatients with schizophrenia: a 2 ...

Drug and Alcohol Dependence 70 (2003) 187 /192 www.elsevier.com/locate/drugalcdep

Smoking and substance abuse in outpatients with schizophrenia: a 2-year follow-up study in Turkey ¨ zcan Uzun a,*, Adnan Cansever a, Cengiz Basog˘lu b, Aytekin O ¨ zs¸ahin a O a

b

Department of Psychiatry, GATA, Etilik, Ankara 06018, Turkey Department of Psychiatry, GATA Haydarpasa, Kadiko¨y, Istanbul 34718, Turkey Received 20 November 2002; accepted 10 December 2002

Abstract Background: This study aimed to determine the prevalence of smoking and substance abuse in outpatients with schizophrenia, and to determine the relationship between smoking status and sociodemographic/clinical characteristics of schizophrenia. Methods: One hundred and thirty-six schizophrenic outpatients were assessed by the structured clinical interview for DSM-IV (SCID) and brief psychiatric rating scale (BPRS). Demographic and treatment variables were obtained from case records and interviews with patients and their family members. Results: The frequency of smoking among schizophrenic patients was 50%. However, the rate of substance abuse was 5.2%. We found no statistically significant differences between the smoker and the non-smoker patients on the demographic variables of age, sex, marital status, and employment status. There was no significant difference between the groups on BPRS scores. However, smokers were receiving a higher daily dose of neuroleptic than non-smokers. Conclusion: The prevalence of smoking among schizophrenic patients was similar to the rates found in Western cultures. However, the prevalence of substance abuse was lower in Turkish patients as compared with patients in the Western population. # 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Schizophrenia; Smoking; Substance abuse; Turkish patients

1. Introduction Cigarette smoking is a major public health problem that causes considerable morbidity and mortality (Fagerstrom, 2002). Several studies from different countries reported high rates of smoking among patients with schizophrenia (Goff et al., 1992; De Leon et al., 1995; Kelly and McCreadie, 1999). Hughes et al. (1986) found the prevalence to be 88%, nearly three times the rate in the general population and higher than the elevated rates of smoking in patients with other psychiatric illnesses. Psychosocial and biological factors might lead to nicotine addiction in schizophrenia (Kelly and McCreadie, 2000). It has been suggested that the high rate of smoking among schizophrenic patients might reflect the effects of institutionalisation, boredom, and poor impulse control. De Leon (1996) speculated that smoking * Fax: /90-312-304-45-07. E-mail address: [email protected] (a.v. Uzun).

might provide some forms of self-medication to compensate for deficits associated with the illness and antipsychotic medications. Results from the Adler et al. (1998) study suggested that increased smoking in schizophrenia might be related to disease-related dysfunction in nicotinic receptors or cholinergic sensory gating deficits. Among patients with schizophrenia, there is an increase in deaths from natural causes. The most common causes are cardiovascular and respiratory diseases, which are both smoking-related (Mortensen and Juel, 1993). In addition to the associated health hazards, cigarette smoking alters drug blood levels and effectiveness, modifies psychiatric symptoms, and is a gateway to other substance abuse (Ziedonis et al., 1994). Smokers with schizophrenia are two to three times more likely to have another substance abuse disorder than non-smokers (Ziedonis et al., 1994). Dual-diagnosed patients have mainly been investigated in USA and European countries. The lifetime prevalence rate of substance abuse among patients with schizophrenia has

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been reported to range from 29 to 55% in these countries (Soyka et al., 1993; Menezes et al., 1996; Swofford et al., 2000). This comorbidity may reflect self-medication as well as a biological susceptibility to both schizophrenia and substance abuse (Kosten and Ziedonis, 1997). Substance abuse may exacerbate psychotic symptoms (Swofford et al., 1996) and contribute to increased hospital admissions (Mueser et al., 1992), poor outcomes (Hambrecht and Hafner, 1996), and poor compliance to treatment (Swofford et al., 1996). There is little information about substance abuse and smoking among schizophrenic patients in various cultures. It has been emphasised that cultural differences can affect the patterns of substance abuse (Compton et al., 2000). Therefore, it may not be appropriate to generalise the American and Western European findings to all the countries. The aims of this study were: (i) to determine the prevalence of smoking and substance abuse in Turkish outpatients with schizophrenia and (ii) to examine the relationship between smoking status and the clinical characteristics of schizophrenia.

2. Method 2.1. Setting The study was carried out at the schizophrenia outpatient unit of the Department of Psychiatry, Gulhane School of Medicine, Ankara, Turkey. Ankara is a city with a population of approximately 3 million people and has seven psychiatric clinics. Although it is a military hospital, both military and civilian patients are treated at Gulhane. Patients do not usually apply to our schizophrenia outpatient unit by themselves. They are normally referred by their family, by an institution, or by other professionals. A psychiatric resident initially evaluates all the patients at the outpatient unit. Patients who have some forms of schizophrenia-spectrum disorder are referred to the schizophrenia outpatient unit. In addition, schizophrenic patients who are discharged from our inpatient unit are also followed-up by the schizophrenia outpatient unit. 2.2. Subjects Subjects who had a concomitant neurological or organic brain syndrome or who were diagnosed with brief drug-related psychoses were not included in the study. The study group consisted of 136 consecutive psychotic patients who fulfilled the diagnostic and statistical manual of mental disorders (DSM-IV) criteria for schizophrenia. Nine patients were first-time admissions and the remaining 127 had been admitted on two

or more occasions. Twenty of the 136 patients (11 of them were smokers) were dropped from the study because we could not contact them during follow-up. One hundred and sixteen subjects completed the study (64 males (55.2%) and 52 females (44.8%)). Of these, 52 subjects (44.8%) were civilians, 32 (27.6%) were relatives of military personnel, 24 (20.7%) were retired military personnel, and another eight (6.9%) were military personnel. Most of them (n/105; 90.5%) had health insurance and only nine subjects needed to pay for health care. The mean age of the patients was 37.99/12.9 years (range: 18 /75 years) and education level was 10.69/3.1 years (range: 5/17 years). Except one subject, all patients were living with their relatives. The subjects were fully informed about the nature of the study procedure, and consent was obtained from each subject before entering the study.

2.3. Baseline assessment This study was carried out by four clinicians (OU, AC, CB, and AO). At the beginning of the study, the subjects were questioned about their sociodemographic background. The diagnosis of schizophrenia was confirmed using the Structured Clinical Interview for DSMIV (SCID) (First et al., 1997), Turkish version (Corapcioglu et al., 1999), and severity of illness was measured using the 18-item Brief Psychiatric Rating Scale from 0 to 6 points (Overall and Gorham, 1962). Non-nicotine substance abuse (that includes alcohol) and smoking behaviour were assessed by a different clinician (AC). Subjects who met the criteria for nonnicotine substance dependence or abuse according to the DSM-IV (American Psychiatric Association, 1994) within the 6-month period prior to assessment were defined as current abusers. Patients who did not meet the criteria for current non-nicotine substance dependence or abuse were considered as non-abusers. Patients were assessed as current smokers if they reported smoking a minimum of five cigarettes a day over the past 6 months (Goff et al., 1992). Those who had never smoked and ex-smokers (who had stopped smoking for more than 6 months before the initial assessment) were defined as non-smokers. In addition, a semi-structured interview was conducted to obtain information about the chronology of illness, smoking, and substance abuse history. Whenever possible, the patient’s history was corroborated by medical records, clinicians, and family members. This method partially circumvented the problem of denial of substance abuse in the mentally ill (Safer, 1987). The treating physician (OU) did not participate in the semi-structured interviews about the substance abuse behaviours of the subjects.


2.4. Two-year assessments Patients were interviewed at regular intervals (once in every 3 months) over a 2-year period. BPRS and other clinical assessments listed above were repeated at each interview. Questions about smoking, substance abuse, treatment compliance (treatment compliance was defined in terms of keeping appointments and taking drugs as recommended), number of hospitalisations, and variations of the neuroleptic dose were also examined at each interview. 2.5. Statistics Differences between both groups concerning sociodemographic and clinical characteristics were compared. To compare the differences between the two groups, ttests and x2-tests (employing Fisher’s exact test when indicated) were performed. A P -value of B/0.05 was considered to indicate statistical significance in all the analyses.

3. Results 3.1. Characteristics of subjects at baseline Fifty-eight patients (50%) were non-smokers. Of the 58 non-smokers, 10 (17.2%) were ex-smokers. Fiftyeight patients (50%) were current smokers. The current smokers reported smoking at an average of 24.99/15.2 (range: 10 /90) cigarettes per day. Eighteen of the current smokers (31%) were heavy smokers (/25 cigarettes per day). Eighty-nine subjects (76.7%) were lifetime teetotallers, and 21 subjects (18.1%) had drunk alcohol at some time. Only six of the 116 patients (5.2%) were current substance abusers. Among these, three patients had a diagnosis of alcohol abuse, two had a diagnosis of alprazolam abuse, and one had a diagnosis of amineptine abuse (amineptine is an antidepressant drug, but is not in the market any longer). Because of the limited number of patients, it was not possible to conduct separate statistical analyses for substance abusers and non-abusers, and they were omitted in the following analyses. Only current smokers were compared with non-smokers on demographic and clinical variables (Table 1). The patients who smoked were more highly educated, as compared with non-smokers (11.39/3.0 years vs. 9.79/3.4 years, t/2.56, d.f. /114, P B/0.012). The differences between smokers and non-smokers on other sociodemographic variables (gender, age, marital status, employment, residence, and housing) were not statistically significant (Table 1). The mean age at which patients started smoking was 21.79/3.8 years (range: 13 /30 years). Although the

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difference was not statistically significant, the age at the onset of illness was lower in smokers (24.69/6.2 years) than in non-smokers (25.39/11.4 years) (t/0.36, d.f. /114, P /0.05). In 38 of the patients (65.5%), smoking initiation occurred before the disease onset. 3.2. Changes of clinical characteristics in the smoker and non-smoker groups during follow-up During the 2-year interval, four of the six substance abusers stopped using alcohol (two patients) or drugs (two patients). However, only one smoker stopped smoking. In the study group, there was no new case of smoking or substance abuse during the 24 months. At the end of the study, among the 116 patients with schizophrenia, two subjects (1.7%) were still substance abusers and 57 subjects (49.1%) were smokers. The number of hospitalisations did not differ between smokers (0.69/1.1) and non-smokers (0.49/0.8) during follow-up period (t/0.858, d.f. /114, P /0.05). The rate of non-compliance to treatment was 34.5% (n /20) in the smoking group and 18.9% (n /11) in the nonsmoking group (Fisher’s exact test, P B/0.05; Table 2). There were no significant differences between smokers and non-smokers on BPRS scores throughout the assessment in 2 years. Except for the baseline assessment, smokers were receiving a significantly higher dose of neuroleptics than non-smokers (Table 2). We found positive correlations between BPRS scores and neuroleptic doses at all assessments.

4. Discussion We found the prevalence of current substance abuse to be 5.2% at the baseline interview and 1.7% at the end of the study. (The prevalence of substance abuse in the Turkish general population is not entirely known. In a previous study, the prevalence of alcohol dependence was found to be 1% in Ankara (Goldberg and Lecrubier, 1995).) Our finding was noteworthy. The prevalence of current substance abuse among patients with schizophrenia has been reported to be between 20 and 35%, approximately, in USA (Dixon et al., 1991; Swofford et al., 2000) and Europe (Menezes et al., 1996; Kamali et al., 2000). None of the results of such studies was as low as our findings. The widely differing reported prevalence rates might be due to a number of variables including definitions, treatment setting, geographical variation (Smith and Hucker, 1994), religion (Miller et al., 2001), legal rules (Chong and Choo, 1996), cultural mores (Ashton and Stepney, 1982), or other social factors. For example, Tessler and Dennis (1989) emphasised a strong association between dual-diagnosis and homelessness. In our study sample, the rate of homelessness was very low (only one subject). Cross-


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Table 1 Sociodemographic data of schizophrenic patients at baseline Characteristics

Smokers (n/58; 50%)

Non-smokers (n/58; 50%)

P

Age; median9/S.D. (years) Education; median9/S.D. (years)

36.99/8.5 11.39/3.0

39.19/2.1 9.79/3.4

0.355* 0.012*

Gender; n (%) Male Female

33 (56.9) 25 (43.1)

31 (53.4) 27 (46.6)

Marital status; n (%) Single Married Divorced/widowed

36 (62.1) 15 (25.8) 7 (12.1)

34 (58.6) 17 (29.3) 7 (12.1)

Residence; n (%) Urban/suburban Rural

47 (81.0) 11 (19.0)

46 (79.3) 12 (20.7)

Employment; n (%) Unemployed Student Employed

47 (81.0) 3 (5.2) 8 (13.8)

53 (91.4) 2 (3.4) 3 (5.2)

Homelessness; n (%)

0

1 (1.7)

0.852***

0.913**

0.816***

0.417**

0.917***

* t -test. ** x2-test. *** Fisher’s exact test.

Table 2 Changes of clinical features of subjects during follow-up Characteristics

Smokers

Non-smokers

P

Number of hospitalisation; median9/S.D. Rate of non-compliance; n (%)

0.69/1.1

0.49/0.8

0.393*

20 (34.5)

11 (18.9)

0.05**

34.49/15.0 33.49/14.8 31.49/14.9 30.19/14.7 29.49/14.9

32.19/13.9 31.39/13.9 30.29/13.7 29.19/13.1 27.29/13.0

0.390* 0.432* 0.642* 0.680* 0.408*

507.39/197.9 485.89/180.0 459.59/171.3 437.99/168.1 401.39/168.3

0.123* 0.049* 0.018* 0.006* 0.000*

BPRS total scores At baseline Sixth month Twelfth month Eighteenth month At the end of 2 years

Mean daily dose of neuroleptic (mg)a At baseline 565.59/205.8 Sixth month 555.29/195.3 Twelfth month 537.19/175.9 Eighteenth month 527.69/179.7 At the end of 2 years 516.49/176.7 a

Chlorpromazine equivalents dose (mg per day). * t -test ** Fisher’s exact test.

cultural studies are clearly required to further evaluate the direction of causal relationship among sociocultural factors and substance abuse. In our study, the rate of smokers was 50% and the rate of heavy smokers was 31%. This finding was consistent with the previous results in the literature

(Diwan et al., 1998; Kelly and McCreadie, 1999), which reported high rates of smoking among schizophrenic patients ranging from 32 to 92%. Smoking rates among schizophrenic patients are two to three times higher than in the Western general population (De Leon et al., 1995; Kelly and McCreadie, 1999). However, our data indicated that the rate of smokers (50%) in our study sample was close to that (43%) in the Turkish general population (WHO Tobacco or Health Programme, 1997). The high rate of smoking in the Turkish general population may be associated with various factors (e.g., national policies, regulations, availability of cigarettes, and sociocultural factors). Social and cultural factors, including the influence of family and friends, the cultural stereotype of the smoker, and the social rewards of smoking, do seem to be important in initiating the habit and maintaining smoking behaviour (Ashton and Stepney, 1982). Gender effects were previously demonstrated in studies of smoking and schizophrenia. In Western studies, there was usually a preponderance of male smokers among patients with schizophrenia (Goff et al., 1992; Kelly and McCreadie, 1999). The rate of smoking in males (63%) is approximately two and a half times higher than females (24%) in the Turkish general population (WHO Tobacco or Health Programme, 1997). However, the rate of male smokers was close to the rate of female smokers in our study sample. In this study, there were no statistically significant differences between the two groups on age, and age at


the onset of the illness. In contrast, the results of previous studies indicated that smokers were more often young and had an earlier onset of illness (Goff et al., 1992; Ziedonis et al., 1994). Our findings have shown that 65.5% of the smokers had started smoking before the onset of their psychiatric illness. This finding was similar to the reports in the literature which indicated that most smokers had started to smoke before the onset of their illness (Sandyk and Kay, 1991). Contrary to the previous studies (Goff et al., 1992; Ziedonis et al., 1994), we did not find a statistically significant difference between the BPRS scores of the smokers and the non-smokers. Except for the baseline comparison, the smokers were receiving a significantly higher dose of neuroleptics than the non-smokers. In addition, there were positive correlations between BPRS scores and neuroleptic doses in our survey. Most surveys have found that the smokers receive a correspondingly higher mean neuroleptic daily dose than the nonsmokers (Decina et al., 1990; Sandyk and Kay, 1991). The postulated explanation is the increased clearance of the neuroleptics as a result of induction of hepatic microsomal enzymes by smoking (Dalack et al., 1998). Therefore, smokers need higher doses of neuroleptics to achieve the same therapeutic effect (Dalack et al., 1998). Our study has several limitations. (i) Because the study was carried out among patients who were usually referred to our outpatient unit, the results may not represent the true prevalence of substance abuse and smoking among patients with schizophrenia. (ii) Findings were not compared with those for a matched group of non-patient controls. Moreover, the prevalence of substance abuse in Turkish general population is not entirely known. (iii) Although psychiatric patients often deny substance abuse even when there is clear evidence to the contrary (Condren et al., 2001), alcohol and other substance abuse disorders were diagnosed by the reports of patients, their relatives, and medical records. Laboratory investigations to test the diagnosis were not performed. In fact, Condren et al. (2001) found that some of the patients with schizophrenia had negative histories for substance abuse but had positive urine test results. This may be one of the possible reasons for our low rates of substance abuse. (iv) Finally, because of the limited number of abuser patients, they were not compared with non-abusers on demographic and clinical variables. The finding of a relatively low rate of substance abuse in Turkish patients with schizophrenia suggests that cultural variations may be a critical determinant in directing patients to abuse drugs. That is, cultural attitudes may play an important role in substance abuse. However, the rate of smoking among our patients with schizophrenia was similar to the results of Western studies.

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References Adler, L.E., Olincy, A., Waldo, M., Harris, J.G., Griffith, J., Stevens, K., Flach, K., Nagamoto, H., Bickford, P., Leonard, S., Freedman, R., 1998. Schizophrenia, sensory gating, and nicotinic receptors. Schizophr. Bull. 24, 189 /202. American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. American Psychiatric Association, Washington, DC. Ashton, H., Stepney, R., 1982. Smoking Psychology and Pharmacology. Tavistock, New York. Chong, S.A., Choo, H.L., 1996. Smoking among Chinese patients with schizophrenia. Aust. NZ J. Psychiatr. 30, 350 /353. Compton, W.M., Cottler, L.B., Ben Abdallah, A., Phelps, D.L., Spitznagel, E.L., Horton, J.C., 2000. Substance dependence and other psychiatric disorders among drug-dependent subjects: race and gender correlates. Am. J. Addict. 9, 113 /125. Condren, R.M., O’Connor, R., Browne, R., 2001. Prevalence and patterns of substance misuse in schizophrenia: a catchment area case /control study. Br. J. Psychiatr. 25, 17 /20. Corapcioglu, A., Aydemir, O., Yildiz, M., Esen, A., Koroglu, E., 1999. Structured Clinical Interview for DSM IV (SCID), Turkish Version. Hekimler Yayin Birligi, Ankara. Dalack, G.W., Healy, D.J., Meador-Woodruff, J.H., 1998. Nicotine dependence in schizophrenia: clinical phenomena and laboratory findings. Am. J. Psychiatr. 155, 1490 /1501. Decina, P., Caracci, G., Sandyk, R., Berman, W., Mukherjee, S., Scapicchio, P.L., 1990. Cigarette smoking and neuroleptic-induced Parkinsonism. Biol. Psychiatr. 28, 502 /508. De Leon, J., 1996. Smoking and vulnerability for schizophrenia. Schizophr. Bull. 22, 405 /409. De Leon, J., Dadvand, M., Canuso, C., White, A.O., Stanilla, J.K., Simpson, G.M., 1995. Schizophrenia and smoking: an epidemiological survey in a state hospital. Am. J. Psychiatr. 152, 453 /455. Diwan, A., Castine, M., Pomerleau, C.S., Meador-Woodruff, J.H., Dalack, G.W., 1998. Differential prevalence of cigarette smoking in patients with schizophrenic vs. mood disorders. Schizophr. Res. 33, 113 /118. Dixon, L., Haas, G., Weiden, P.J., Sweeney, J., Frances, A.J., 1991. Drug abuse in schizophrenic patients: clinical correlates and reasons for use. Am. J. Psychiatr. 148, 224 /230. Fagerstrom, K., 2002. The epidemiology of smoking: health consequences and benefits of cessation. Drugs 62 (Suppl. 2), 1 /9. First, M.B., Spitzer, R.L., Williams, J.B.W., 1997. Structured Clinical Interview for DSM-IV (SCID). American Psychiatric Association, Washington, DC. Goff, D.C., Henderson, D.C., Amico, E., 1992. Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am. J. Psychiatr. 149, 1189 /1194. Goldberg, D.P., Lecrubier, Y., 1995. Form and frequency of mental ¨ stu¨n, T.B., Sartorius, N. (Eds.), disorders across centres. In: U Mental Illness in General Health Care: An International Study (on behalf of WHO). Wiley, Chichester, pp. 323 /334. Hambrecht, M., Hafner, H., 1996. Substance abuse and the onset of schizophrenia. Biol. Psychiatr. 40, 115 /116. Hughes, J.R., Hatsukami, D.K., Mitchell, J.E., Dahlgren, L.A., 1986. Prevalence of smoking among psychiatric outpatients. Am. J. Psychiatr. 143, 993 /997. Kamali, M., Kelly, L., Gervin, M., Browne, S., Larkin, C., O’Callaghan, E., 2000. The prevalence of comorbid substance misuse and its influence on suicidal ideation among inpatients with schizophrenia. Acta Psychiatr. Scand. 101, 452 /456. Kelly, C., McCreadie, R.G., 1999. Smoking habits, currents symptoms, and premorbid characteristics of schizophrenic patients in Nithsdale, Scotland. Am. J. Psychiatr. 156, 1751 /1757.

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Kelly, C., McCreadie, R.G., 2000. Cigarette smoking and schizophrenia. Adv. Psychiatr. Treat. 6, 327 /331. Kosten, T.R., Ziedonis, D.M., 1997. Substance abuse and schizophrenia. Schizophr. Bull. 23, 181 /186. Menezes, P.R., Johnson, S., Thornicroft, G., Marshall, J., Prosser, D., Bebbington, P., Kuipers, E., 1996. Drug and alcohol problems among individuals with severe mental illness in south London. Br. J. Psychiatr. 168, 612 /619. Miller, L., Weissman, M., Gur, M., Adams, P., 2001. Religiousness and substance abuse in children of opiate addicts. J. Subst. Abuse 13, 323 /336. Mortensen, P.B., Juel, K., 1993. Mortality and causes of death in first admitted schizophrenic patients. Br. J. Psychiatr. 163, 183 /189. Mueser, K.T., Bellack, A.S., Blanchard, J.J., 1992. Comorbidity of schizophrenia and substance abuse: implications for treatment. J. Consult. Clin. Psychol. 60, 845 /856. Overall, J.E., Gorham, D.R., 1962. Brief psychiatric rating scale. Psychol. Rep. 10, 799 /812. Safer, D.J., 1987. Substance abuse by young adult chronic patients. Hosp. Commun. Psychiatr. 38, 511 /514. Sandyk, R., Kay, S.R., 1991. Tobacco addiction as a marker of age at onset of schizophrenia. Int. J. Neurosci. 57, 259 /262.

Smith, J., Hucker, S., 1994. Schizophrenia and substance abuse. Br. J. Psychiatr. 165, 13 /21. Soyka, M., Albus, M., Kathmann, N., Finelli, A., Hofstetter, S., Holzbach, R., Immler, B., Sand, P., 1993. Prevalence of alcohol and drug abuse in schizophrenic inpatients. Eur. Arch. Psychiatr. Clin. Neurosci. 242, 362 /372. Swofford, C.D., Kasckow, J.W., Scheller-Gilkey, G., Inderbitzin, L.B., 1996. Substance abuse: a powerful predictor of relapse in schizophrenia. Schizophr. Res. 20, 145 /151. Swofford, C.D., Scheller-Gilkey, G.S., Miller, A.H., Woolwine, B., Mance, R., 2000. Double jeopardy: schizophrenia substance abuse. Am. J. Drug Alcohol Abuse 26, 343 /353. Tessler, R.C., Dennis, D.L., 1989. A Synthesis of NIMH-funded Research Concerning Persons Who are Homeless and Mentally Ill. NIMH Division of Education and Service System Liaison, Washington, DC. WHO Tobacco or Health Programme, 1997. A Global Status Report: Country Profiles by Region. Ziedonis, D.M., Kosten, T.R., Glazer, W.M., Frances, A.J., 1994. Nicotine dependence and schizophrenia. Hosp. Commun. Psychiatr. 45, 204 /206.