Smoking Linked to Higher Levels of Psychosis Symptoms

Smoking does not relieve symptoms of psychosis; on the contrary, it may actually worsen positive and depressive symptoms, new research shows.

These findings, investigators say, disprove the hypothesis that the high prevalence of smoking in this patient population is due to "self-medication."

Investigators compared adult patients with non-affective psychosis to unaffected siblings and healthy controls and found that at baseline, close to 70% were smokers, compared with roughly a third of siblings and a quarter of controls.

Smoking was associated with increased positive, negative, and depressive symptoms as well as lower quality of life (QOL) in patients as well as in siblings, as compared to non-smoking patients and siblings — although patients experienced more symptoms than siblings.

Participants were followed for a 6-year period. During this time, patients who started to smoke showed a significant increase in symptoms, especially positive symptoms. On the other hand, smoking cessation was not associated with changes in symptoms or QOL.

"With respect to smoking and long-term symptoms levels and quality of life, we did not find any empirical support for self-medication," lead author Jentien Vermeulen, MD, a PhD candidate in psychiatry at Amsterdam UMC, University of Amsterdam, the Netherlands, told Medscape Medical News.

Rather, said Vermeulen, it appears patients with psychosis who smoke do not experience improved cognitive functioning, symptoms, or quality of life but "actually suffer more."

The study was published online December 5 in Lancet Psychiatry.

Treatment Hindered

"The prevalence of smoking is extremely high in individuals with psychotic disorder," Vermeulen said.

"Some clinicians and researchers postulate that this can be explained because of potential benefits from nicotine and/or tobacco for individuals with psychosis, also known as self-medication. This belief hinders implementation of treatment programs to help patients quit smoking," she said.

Vermeulen and colleagues previously studied whether smoking improves cognition in people with psychosis and found no longer-term benefit, but instead an exacerbation of cognitive symptoms. The current study was designed "to investigate whether there were any long-term benefits regarding symptom levels or quality of life for smokers, compared to nonsmokers."

The researchers drew on participants within the Genetic Risk and Outcome of Psychosis (GROUP) cohort, consisting of patients with nonaffective psychotic spectrum diagnosis, their parents, unaffected siblings, and controls.

Based on the assumptions of the self-medication hypothesis, the researchers expected that smoking in patients with a psychotic disorder would be negatively associated with symptoms and positively associated with QOL.

The final sample consisted of 1984 patients with a noneffective psychotic disorder (66% with schizophrenia), 1047 siblings, and 157 controls.

Of the patients, 67% smoked an average of 17.5 (standard deviation [SD], 8.8) cigarettes per day, which was higher than the percentage smoked among siblings and controls (38% and 25%, respectively).

Mixed-effects analyses found that in patients, smoking was associated with more frequent self-rated positive, negative, and depressive symptoms (estimates 0.140 [standard error (SE), 0.024]; 0.145 [SE, 0.027]; and 0.120 [SE, 0.028], all Ps < .0001), compared with not smoking.

Smoking was also associated with lower quality of life (–0.59 [SE, 0.11], P < .0001 in patients; –0.31 [SE, 0.09], P = .0002 in siblings), compared with not smoking.

Lower Quality of Life

In siblings, significant associations were found between smoking and more frequent subclinical symptoms, while in controls, there was a significant association between smoking and more frequent subclinical positive and depressive symptoms.

Smoking and a higher number of cigarettes per day were associated with a higher frequency of self-rated symptoms (except for depressive symptoms) and a lower QOL across all three groups, when adjusting for age and sex, the authors report.

These "significant results" regarding positive (but not negative) psychosis symptoms and emotional distress were confirmed with clinician-rated PANSS data in patients, but not for negative symptoms.

The findings were not significantly affected when the researchers conducted analyses that accounted for covariates, including years of education and cannabis use in all groups and antipsychotic medication use and level of functioning covariates in patients.

Among patients, siblings, and controls, most participants did not change their smoking behavior from their previous assessments (89%, 86%, and 91%, respectively).

Over time, more participants quit than started smoking (patients, 7% vs 4%; siblings, 8% vs 6%; controls, 5% vs 4%, respectively).

Across all time points, the number of cigarettes per day increased by 0.4 (9.3) in patients, compared to siblings and controls who showed a decrease of 0.2 (5.3) and 0.2 (4.1), respectively.

In patients, starting to smoke was associated with an increase of self-rated positive, negative, and depressive symptoms, but not with QOL, compared with the overall decrease of symptoms in those who did not change their smoking status.

Coping Strategy

In contrast, in unaffected siblings and controls, there were no significant associations between starting to smoke and subclinical symptom frequency or quality of life.

After adding all covariates to the model, only the association between starting to smoke and an increase in positive symptoms remained significant (estimate 0.161 [SE, 0.077], P = .0381).

Post hoc analyses found that in the subgroup of patients for whom chlorpromazine equivalents could be calculated, smokers used significantly higher antipsychotic doses than did nonsmokers.

Significant associations were also found between smoking and symptom levels in the subgroups of patients who used clozapine and in patients who used olanzapine and other antipsychotics.

Vermeulen noted that the investigators "could not assess acute effects of smoking."

She noted that smoking can be an "adverse stress-coping behavior strategy" and that, "with the right motivational interviewing strategy, we could try and help to learn to replace this by healthy coping strategies."

She suggested several potential explanations for the high prevalence of smoking in individuals with psychosis, including the "shared vulnerability hypothesis."

This means that there are "common genetic and environmental risks for developing both psychosis and nicotine addiction," she said.

Another is that "smoking is a risk factor for developing psychosis."

Concerns About E-Cigarettes

Commenting on the study for Medscape Medical News, James Scott, MD, conjoint association professor, School of Public Health, University of Brisbane, Australia, who was not involved in the study, said the findings "discount or disprove a long-standing theory that the reason there is such a high prevalence of smoking [among people with psychotic disorders] is to make them feel less distressed and anxious and improve their symptoms."

Instead, this study "shows robustly that those people with schizophrenia who smoked had a worsening of their symptoms."

He noted that "beyond the physical harm caused by smoking, we should really be concerned about smoking in people with schizophrenia because it affects their mental health, not only their physical health."

Scott, who is the author of a recently published analysis suggesting a causal relationship between tobacco smoking and schizophrenia, suggested that nicotine may be the culprit because it has "significant effects on brain function."

He added that a rising concern is the popularity of e-cigarettes, which are being marketed to nonsmoking young people as "safer" and are being flavored to make them more appealing.

"If nicotine predisposes vulnerable individuals to psychosis, it doesn't matter whether it is in combustible or e-cigarette form," he said.

Vermeulen emphasized that there is "a need for more research into this field to find the most plausible explanation for the high prevalence of smoking in individuals with psychosis, [so as] to tailor prevention and intervention programs."

In an accompanying editorial, lead author Gemma M. J. Taylor, PhD, at the University of Bath, United Kingdom, notes that future research should focus on identifying mechanisms through which smoking affects mental health.

Determining whether the impact on mental health is mediated through nicotine or through some other constituent of tobacco smoke "will inform public health policy around the use of e-cigarettes in psychiatric populations," the editorial authors conclude.

The study was funded by Dutch Health Research Council, Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag, Academic Psychiatric Center of the Academic Medical Center, GGZ inGeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Center Amsterdam, GGZ Noord Holland Noord, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht, Parnassia Psycho-medical Center, Maastricht University Medical Center, GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET GGZ, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem, University Medical Center Utrecht, Altrecht, GGZ Centraal, and Delta.

Vermeulen has disclosed no relevant financial disclosures. The other authors' disclosures are on the original paper. Scott declares no competing interests. The editorial authors report receiving grants from Pfizer, outside of the submitted work.

Lancet Psychiatry. Published online December 5, 2018. Abstract, Editorial

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