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Smoking is associated with greater symptom load in bipolar disorder patients

Mohamedlatif Saiyad, MD

Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY, USA

Rif S. El-Mallakh, MD

Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY, USA

BACKGROUND: Individuals with mental illness have a higher prevalence of smoking than those without a mental illness. Nicotine has several effects on mood and cognition. After many studies, the nature of the effect of smoking on mental illness is not clear.

METHODS: We performed a cross-sectional study of smoking status and symptom load in an outpatient bipolar disorder population. Data were collected and analyzed from 134 outpatients regarding smoking status and symptom profile and severity using the Rapid Psychiatric Interview Data scale.

RESULTS: Smokers had more severe anxiety symptoms (5.2 ± 7.6 vs 2.2 ± 3.3, z = 3.8, P = .0001), depressive symptoms (9.0 ± 9.6 vs 6.5 ± 8.1, z = 3.2, P = .0015), and manic symptoms (3.0 ± 4.2 vs 1.5 ± 2.9, z = 2.1, P = .04) than nonsmokers.

CONCLUSION: Smokers with bipolar disorder carry a greater symptom burden than nonsmokers. However, this is an associational study, and the true nature of the relationship is not clear.

KEYWORDS: anxiety, bipolar disorder, depression, mania, smoking



Smoking is one of the primary preventable causes of death.1,2 Among U.S. adults age ≥18, 19.3% smoke cigarettes.3 However, smoking is not equally distributed among the population. Nearly 44.3% of all cigarettes in the United States are purchased by mentally ill individuals,4 implying that compared with the general population, persons with mental illness are twice as likely to smoke, smoke more cigarettes, or both.4 Bipolar disorder (BD) patients are 2 to 3 times more likely to initiate smoking and are less successful in maintaining abstinence than the general population.5 There is evidence that smokers with BD may suffer more psychiatric problems than nonsmoking BD patients. For example, adolescents who smoke may be more likely to start using alcohol and marijuana in the year after diagnosis compared with nonsmoking adolescents.6 BD patients who smoke are 5 times more likely to have attempted suicide than nonsmoking BD patients.7,8 In general, smoking is associated with greater psychiatric illness burden9-12 and poorer response to treatment.13

We wanted to examine the relationship between smoking and symptom burden in BD. We elected to examine the relationship in a cross-sectional examination of BD patients in routine treatment. This approach would allow us to determine if the documented harmful association with smoking is evident in a random clinical sample.


We collected data from 134 outpatients in a BD clinic. All active patients’ charts were reviewed, and no selection was made on the basis of smoking status. All patients met criteria for bipolar I disorder (BD I), bipolar II disorder (BD II), or bipolar disorder not otherwise specified (BDNOS) as defined by DSM-IV. However, we did not use a structured diagnostic interview to confirm BD or to detect any comorbid conditions. Smoking was defined according to the Centers for Disease Control and Prevention criteria (smoked ≥100 cigarettes in their lifetime and who were smoking every day or some days at the time of interview).14

Patients’ symptoms were scored for mania, depression, and anxiety utilizing Rapid Psychiatric Interview Data scale (RaPID),15 a scale developed for clinical care that resembles the clinical monitoring form used in the Systematic Treatment Enhancement Program for Bipolar Disorder.16 Both scales are brief, can be performed quickly in the clinical setting, and assess specific symptoms of mania and depression separately. The RaPID has high agreement with the Montgomery-Åsberg Depression Rating Scale17 (Lin coefficient = 0.854, 95% CI = 0.788 to 0.919, P < .0001) and the Young Mania Scale18 (Lin coefficient = .531, CI = 0.358 to 0.704, P < .0001).

Demographic data were analyzed with simple non-paired, 2-tailed t tests for continuous variables, and chi-square for categorical variables. Other continuous variables were examined with the nonparametric Mann-Whitney U test. Simple regression analysis was performed to examine how some continuous variables are related to each other. Proportional data were examined with a test for proportions.19 An α < .05 was employed as a threshold for statistical significance.


Of the 134 patients, 92 (68.7%) were female and 42 were male (31.3%). The mean age was 46.3 ± 14.5 (range 18 to 84). There was no difference in age between men (44.4 ± 16.2) and women (47.2 ± 13.7) (t = 1.02, P = .31). This overall rate is similar to previously reported U.S. populations20 but lower than other populations.21-23 There were no differences in smoking rates between the sexes (men 38.1%, women 32.6%, χ2 = .39, P = .54). The majority of patients had BD I (57.5%, BD II = 36.6%, BDNOS = 6.0%). None of these diagnoses were more likely to be associated with smoking (BD I = 33.8%, BD II = 36.7%, BDNOS = 25.0%, χ2 = 0.5, P = .8). Patients who smoked consumed an average of 22.9 ± 28.9 cigarettes/d. Almost all of the patients were on a mood stabilizer and an antipsychotic, and there were no differences in the number of psychotropic medications prescribed to a nonsmoker (3.0 ± 1.4) and smoker (2.9 ± 1.4) (t = 0.5, P = .61).

Patients who smoked had more anxiety symptoms (5.2 ± 7.6 vs 2.2 ± 3.3, U = 5526.0, z = -3.8, P = .0001) (TABLE). They also exhibited more depressive symptoms (9.0 ± 9.6 vs 6.5 ± 8.1, U = 5856.0, z = -3.2, P = .0015), manic symptoms (3.0 ± 4.2 vs 1.5 ± 2.9, U = 6520, z = -2.1, P = .04), and combined depressive plus manic mood symptoms (11.9 ± 11.4 vs 8.0 ± 9.1, U = 9711.5, z = -3.36, P = .0008) (TABLE). No patients attempted suicide or were hospitalized for suicidal ideation during the 3 months of the cross-sectional time period. There was no relationship between the number of cigarettes smoked and severity of depressive symptoms (r2 = .001, P = .7), manic symptoms (r2 = .007, P = .2), or anxiety symptoms (r2 = .001, P = .6). Patients met numerical criteria for an active depressive episode—defined as a depression score >15 on the RaPID—in 63 out of 264 visits (23.9%). There were 18 smoking patients who exhibited depression in 49 visits, and 14 nonsmoking patients that were depressed in 14 visits. This means that patients who smoked accounted for 77.8% of all documented episodes of depression compared with 22.2% among nonsmoking patients (z = 2.25, P > .05). There was no difference in the severity of the depression between the smoking (22.2 ± 6.9) and the nonsmoking patients (22.1 ± 6.0, t = .07, P = 1.0). Fifteen patients met criteria for mania—defined as ≥10 on the mania score of RaPID—of which 12 were patients who smoked (80%) (z = 3.34, P > .05). Smoking patients met criteria for mania in 17 out of 19 visits. Mania severity was not different among patients who smoked (15.7 ± 4.8) and those who did not (14.5 ± 2.1, t = 0.3, P = .7).


Variables examined among smoking and nonsmoking bipolar disorder patients

  Smokers (average ± SD) Nonsmokers (average ± SD) P (t or z)
Age, years 47.3 ± 10.4 46.8 ± 15.2 .7 (0.33)
Sex, % male 29.5% 34.1% .45
Number of psychotropics 2.9 ± 1.4 3.0 ± 1.4 .47 (0.72)
Anxiety symptoms 5.2 ± 7.6 1.5 ± 2.9 .0001 (3.8)
Depressive symptoms 9.0 ± 9.6 6.5 ± 8.1 .0015 (3.2)
Manic symptoms 3.0 ± 4.2 1.5 ± 2.9 .036 (2.28)
Total mood symptoms 11.9 ± 11.4 8.0 ± 9.1 .0008 (3.38)
SD: standard deviation.


The present study shows that patients with bipolar illness who smoke have more psychiatric symptoms than BD patients who do not smoke. Specifically, smokers tend to have more anxious, depressive, and manic symptoms. Patients with bipolar illness who smoke tend to experience more full syndromal depressive and manic episodes compared with nonsmokers but this did not reach statistical significance. This lack of difference may be related to the outpatient setting of this study because severely ill patients are more likely to have been hospitalized.

These findings are similar to previous reports of increased symptom load in BD patients who smoke.10-12 Similarly, previous literature has shown that smoking is associated with unfavorable prognosis, an increased risk for suicidal ideation,11 and poorer medication response.13 We did not examine suicidal ideation in our patients; however, there were no hospitalizations for suicide attempts and no completed suicides among the patients studied within the previous 3 months. Reduced response to medication may be related to reports that smoking may decrease the effect of antipsychotics.24 Alternatively, first-generation antipsychotics are associated with increased quantity of cigarettes consumed, whereas second-generation antipsychotics are associated with reduced basal smoking.25 In our sample there was no difference between the number of psychotropics prescribed to smoking and nonsmoking BD patients.

Interestingly, we have replicated previous studies20 reporting that approximately 35% of U.S. BD patients smoke, which is less than other countries such as Spain, Israel, Turkey, and Columbia, where smoking rates are closer to 50%.21-23,26 This may be related the Surgeon General’s effort to reduce smoking in the United States.27

Although smoking appears to be associated with increased overall symptom burden in BD patients,9-12 there is little evidence that smoking is associated with more episodes of bipolar illness. In our study, patients who smoked had more episodes of bipolar illness than patients who did not smoke, but this difference was not statistically significant. Furthermore, the nature of the association remains unknown. In a longitudinal study of adolescents after an index hospitalization, youths who smoked did not have an increased risk of rehospitalization within a year.6 However, youths who smoked were more likely to abuse other substances, such as alcohol and marijuana.6,28 Comorbid BD and substance abuse may partially underlie the association between smoking and symptom burden. Other potential reasons for the association of smoking and heightened symptom burden include pharmacologic effects24,25 and genetic variants29 or because more severely ill patients are more likely to smoke. All of these factors may underlie the association, making smoking status secondary. We were not able to study these variables in our sample. Our study design did not address why a relationship between symptom burden and smoking status exists.

Smoking combined with other risk factors increases medical comorbidity in BD patients21,30 and reduces life expectancy.31 Smoking cessation should be included in interventions to reduce risk of concomitant medical illness.32 Although most BD patients who smoke want to stop,33 quit attempts are less common26 and usually are less successful than in the general population.5 Varenicline is the most recent smoking cessation aid, but it may be associated with mania induction.34,35 In a placebo-controlled study of bupropion in 5 BD patients, 2 of the placebo-treated patients, and 1 of the bupropion-treated patients developed hypomanic symptoms.36 Only 1 of the 2 patients randomized to bupropion maintained abstinence.36 Until generalizable controlled studies for BD patients are available, attempts to stop smoking utilize standard interventions including psychotherapeutic methods, nicotine replacement, varenicline, and bupropion.37 We did not examine attempts to quit smoking in this cross-sectional study.

There are limitations to our study, which is retrospective, cross-sectional, and did not prospectively define the variables collected. The study did not examine the causal relationship between smoking and BD symptoms, and there are many confounding factors that could explain the greater symptom load, such as increased substance use and medical illness. We did not use an objective measure of smoking and information on smoking status was obtained by self-report. Despite these limitations, the results of the current study are in line with previous reports that document a relationship between smoking and symptom burden in BD patients.


There is a significant difference of psychiatric symptoms between BD patients who smoked and those who did not. Patients who smoke have a greater symptom load, particularly for manic and anxiety symptoms. More research is needed to elucidate the nature of the association between smoking and symptom load in these patients.

DISCLOSURES: Dr. Saiyad reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. El-Mallakh is on the speakers’ bureau of AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis. This study was not funded by an extramural source, and the University of Louisville supported the investigators.


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CORRESPONDENCE: Rif S. El-Mallakh, MD, Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, 501 E. Broadway, Suite 340, Louisville, KY 40202 USA E-MAIL: rselma01@louisville.edu