Commentary

A street medicine view of tobacco use in patients with schizophrenia

Current Psychiatry. 2023 October;22(10):e3-e5 | doi: 10.12788/cp.0404

John W. Figg, BS

Jake A. Surges, BA

Yasmeen Murtaza, BS

Bayli DiVita Dean, PhD

Ana Turner, MD

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References

1. Patkar AA, Gopalakrishnan R, Lundy A, et al. Relationship between tobacco smoking and positive and negative symptoms in schizophrenia. J Nerv Ment Dis. 2002;190(9):604-610. doi:10.1097/00005053-200209000-00005

2. Ding JB, Hu K. Cigarette smoking and schizophrenia: etiology, clinical, pharmacological, and treatment implications. Schizophr Res Treatment. 2021;2021:7698030. doi:10.1155/2021/7698030

3. Kendler KS, Lönn SL, Sundquist J, et al. Smoking and schizophrenia in population cohorts of Swedish women and men: a prospective co-relative control study. Am J Psychiatry. 2015;172(11):1092-1100. doi:10.1176/appi.ajp.2015.15010126

4. Patel KR, Cherian J, Gohil K, et al. Schizophrenia: overview and treatment options. P T. 2014;39(9):638-645.

5. King M, Jones R, Petersen I, et al. Cigarette smoking as a risk factor for schizophrenia or all non-affective psychoses. Psychol Med. 2021;51(8):1373-1381. doi:10.1017/S0033291720000136

6. Sagud M, Mihaljevic Peles A, Pivac N, et al. Smoking in schizophrenia: recent findings about an old problem. Curr Opin Psychiatry. 2019;32(5):402-408. doi:10.1097/YCO.0000000000000529

7. Quigley H, MacCabe JH. The relationship between nicotine and psychosis. Ther Adv Psychopharmacol. 2019;9:2045125319859969. doi:10.1177/2045125319859969

8. Balfour DJ, Ridley DL. The effects of nicotine on neural pathways implicated in depression: a factor in nicotine addiction? Pharmacol Biochem Behav. 2000;66(1):79-85. doi:10.1016/s0091-3057(00)00205-7

9. Wang P, Abdin E, Asharani PV, et al. Nicotine dependence in patients with major depressive disorder and psychotic disorders and its relationship with quality of life. Int J Environ Res Public Health. 2021;18(24):13035. doi:10.3390/ijerph182413035

10. Popik P, Krawczyk M, Kos T, et al. Nicotine produces antidepressant-like actions: behavioral and neurochemical evidence. Eur J Pharmacol. 2005;515(1-3):128-133. doi:10.1016/j.ejphar.2005.04.009

11. Quattrocki E, Baird A, Yurgelun-Todd D. Biological aspects of the link between smoking and depression. Harv Rev Psychiatry. 2000;8(3):99-110.

12. Pal A, Balhara YP. A review of impact of tobacco use on patients with co-occurring psychiatric disorders. Tob Use Insights. 2016;9:7-12. doi:10.4137/TUI.S32201

13. Prochaska JJ, Das S, Young-Wolff KC. Smoking, mental illness, and public health. Annu Rev Public Health. 2017;38:165-185. doi:10.1146/annurev-publhealth-031816-044618

14. Coustals N, Martelli C, Brunet-Lecomte M, et al. Chronic smoking and cognition in patients with schizophrenia: a meta-analysis. Schizophr Res. 2020;222:113-121. doi:10.1016/j.schres.2020.03.071

15. Stolz PA, Wehring HJ, Liu F, et al. Effects of cigarette smoking and clozapine treatment on 20-year all-cause & cardiovascular mortality in schizophrenia. Psychiatr Q. 2019;90(2):351-359. doi:10.1007/s11126-018-9621-4

16. Tsoi DT, Porwal M, Webster AC. Interventions for smoking cessation and reduction in individuals with schizophrenia. Cochrane Database Syst Rev. 2013;2013(2):CD007253. doi:10.1002/14651858.CD007253.pub3

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18. Han B, Aung TW, Volkow ND, et al. Tobacco use, nicotine dependence, and cessation methods in us adults with psychosis. JAMA Netw Open. 2023;6(3):e234995. doi:10.1001/jamanetworkopen.2023.4995

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Throughout my psychiatric clerkship, I (JWF) participated in street medicine, the practice of providing care to patients (typically those who are homeless) at the location they currently reside, such as in a homeless encampment or community shelter. Our clinical team drove to locations that provided housing for patients diagnosed with schizophrenia, where we assisted with medications and blood draws. I remember pulling up the first day and seeing someone outside smoking a cigarette. I soon learned that many people living in such situations were smokers, and that among the substances they used, tobacco was the most common.

One patient said the cigarettes helped him manage the “voices in his head” as well as some of the adverse effects from medication, such as parkinsonism and akathisia. I asked my attending physician about this and she explained that for some patients, using tobacco was a way to mitigate the positive symptoms of schizophrenia and make the adverse effects of their therapy, particularly extrapyramidal symptoms (EPS), more bearable. By the end of my 2-week rotation, I was sure of a trend: our patients with schizophrenia smoked incessantly. Near the end of my rotation, I asked a patient, “Why do you smoke”? The patient looked at me, puzzled, and replied: “I just do.” This exchange only piqued my curiosity, and I could not help but wonder: what is the relationship between tobacco use and schizophrenia? How is tobacco use related to the pathophysiology of schizophrenia? Does tobacco use among patients with schizophrenia ameliorate aspects of their psychosis? Street medicine offered me a window into a biomedically intriguing question, and I wanted to learn more.

What smoking does for patients with schizophrenia

The high prevalence of smoking among patients with schizophrenia (50% to 88%) greatly exceeds the rates of smoking among patients with other psychiatric illnesses.^1,2 The role of smoking in relation to schizophrenia and other psychoses is multidimensional, and evidence implicates smoking as a risk factor for schizophrenia.^3,4

Two mechanisms may help explain tobacco use in patients with schizophrenia: reducing the adverse effects of antipsychotic medications and promoting neural transmission of dopamine. Second-generation antipsychotics (SGAs) are a first-line treatment, but they can produce EPS, metabolic dysregulation, and blood disorders such as hyponatremia and (rarely) agranulocytosis (1% with clozapine).⁵ Compared to those who are nonsmokers, patients with schizophrenia who smoke are more likely to experience more severe symptoms (eg, hallucinations and delusions) and less severe EPS.^5,6 Research suggests that exposure to polycyclic aromatic hydrocarbons released during smoking induces cytochrome P450 1A2, an enzyme that metabolizes antipsychotic medications such as haloperidol, clozapine, and olanzapine. Increased metabolism results in lower serum concentrations of antipsychotics, lower efficacy, and more severe positive symptoms.^5,6

Additionally, tobacco is an activator of nicotinic acetylcholine receptors (nAChR).⁶ When these receptors become activated, dopamine is released. Dopamine serves as a mediator of reward for nicotine use. In the context of schizophrenia, tobacco use opposes the mechanism of action of SGAs, which is to block neural transmission of dopamine.⁶ The etiology of EPS is related to the blockade of postsynaptic dopamine release in the striatum.⁶ By activating nAChR, smoking induces a downstream release of dopamine that can alleviate iatrogenic EPS by restoring neural transmission of dopamine.⁶ Nicotine may also modulate alpha-7 nicotinic receptor dysfunction, and improve the ability to filter out irrelevant environmental stimuli (impaired sensory gating), which can be overwhelming for patients with schizophrenia. It also can improve cognitive dysfunction and attention by inducing the release of dopamine in mesocortical pathways.⁷ The implications of this neural pathway are significant because smoking is significantly greater in tobacco users who are diagnosed with schizophrenia compared to tobacco users who lack a psychiatric diagnosis.^6,7 Smoking may enhance dopaminergic neural transmission to a far greater extent in tobacco users with schizophrenia compared to tobacco users who do not develop schizophrenia, which suggests intrinsic differences at the neuronal level. Neural differences between tobacco users with or without schizophrenia may synergize with smoking in clinically and biologically meaningful ways. These pathways require further research to support or disprove these hypotheses.

Aside from the dopaminergic system, mechanisms influencing tobacco use among patients with schizophrenia may also be related to nicotine’s mild antidepressant effects. Evidence suggests a clinically meaningful association between nicotine dependence and mood disorders, and this association may be due to the antidepressant effects of nicotine.^8-13 Patients with schizophrenia may experience respite from depressive symptoms through their tobacco use, eventually leading to nicotine dependence.

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