Burning Need to Help Patients With Schizophrenia Quit Smoking

Fran Lowry

April 23, 2019

ORLANDO, Florida — Helping patients with schizophrenia who smoke kick their tobacco addiction is a matter of life or death, experts say.

Not only do patients with schizophrenia smoke at a much higher rate than the general population, but smoking is a major cause of premature death in these patients, making effective cessation treatments essential.

Dr Faith Dickerson

"Individuals with schizophrenia are approximately three times more likely to smoke cigarettes than those in the US general population. They are also heavier smokers and have a more difficult time quitting," said Faith Dickerson, PhD, Sheppard Pratt Health System, Baltimore, Maryland.

"So any effect that we find in the general population is going to be amplified in schizophrenia because still, even in 2019, more than 60% of persons with schizophrenia smoke; and overall, 40% of the cigarettes in the US are smoked by persons with a mental health disorder," Dickerson said.

Dickerson and others were presenting their research at a smoking-focused symposium here at the Congress of the Schizophrenia International Research Society (SIRS) 2019.

Myths Abound

During her presentation, Dickerson debunked several myths about smoking and individuals with schizophrenia.

"These myths abound — people with schizophrenia are not able to quit, they don't want to quit, they get worse if they quit, the smoking alleviates some of their symptoms in some way. There is the erroneous but still somewhat widespread belief that somehow we are going to add to their life hardship...by getting them to quit smoking," she said.

"Observational data have contributed to the idea that smoking may be a form of self-medication for cognitive deficits and emotional distress in people with schizophrenia, but newer data refute that notion," she added.

Dickerson presented data from two cohort studies about the association between smoking and cognitive functioning and about smoking and suicide attempts.

The first cohort consisted of 861 patients with schizophrenia, 450 patients with other serious mental illnesses, and 587 individuals without psychiatric illness who served as healthy control participants.

Cognitive function was assessed in all participants with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Results showed that smoking was significantly and inversely associated with the total RBANS cognitive score for the overall sample (P = .002) and for those with schizophrenia (P = .001) after adjusting for age, sex, race, and maternal education, which was used as a proxy for premorbid socioeconomic status.

In the group with schizophrenia, a significant and inverse association was found for scores on the RBANS Immediate Memory (P = .003), Visual Constructional (P = .003), and Attention (P = .005) scales, but not on the Delayed Memory or Language scales.

In addition, the link between smoking and cognitive functioning was largely unchanged when the researchers adjusted for the severity of psychiatric symptoms.

Link to Suicide Attempts

In the second cohort, 253 patients with schizophrenia or other serious mental illness were assessed with the Columbia Suicide Severity Rating Scale.

Results showed a significant association between current smoking status and a history of suicide attempts in the overall group (odds ratio [OR], 2.80; P < .001) and in the group with schizophrenia (OR, 2.25; P = .047), after adjusting for age, race, and sex.

A third cohort consisted of 789 individuals with schizophrenia who were assessed and then followed up with regard to their mortality and cause of death after an average period of 8 years.

Smoking at baseline was the strongest predictor of natural cause mortality. The relative risk (RR) was increased more than twofold for the smokers (RR, 2.29; P < .001).

Nicotine may improve some aspects of attention and concentration in the short term, but the long-term cognitive effects are harmful; it is linked to more suicide; and it is the strongest modifiable cause of premature mortality in people with schizophrenia — highlighting why smoking cessation needs to be a high treatment priority for these patients, Dickerson said.

"The notion that people with schizophrenia can't stop smoking should be put to rest," she added.

Does Smoking Cause Psychosis?

In a second presentation, Robin Murray, MD, professor of psychiatry at King's College Hospital, London, United Kingdom, said it seems likely that smoking tobacco is a causal factor of psychosis. However, he cautioned that it's too early to know that for sure.

Dr Robin Murray

His previous research showed an association between heavy cannabis use in young people and subsequent high risk of developing schizophrenia.

His team recently conducted a systematic review and meta-analysis of 61 case-control and prospective studies to test two hypotheses: that daily tobacco use is associated with an increased risk for psychotic illness, and that smoking is associated with an earlier age at onset of psychotic illness.

The study sample of patients with psychotic disorders included 14,555 tobacco users and 273,162 nonusers.

Results showed that the prevalence of smoking in patients presenting with first-episode psychosis (FEP) was 0.57 (95% confidence interval [CI], 0.52 – 0.62; P < .0001).

In addition, persons who smoked daily developed psychotic illness about a year earlier than nonsmokers (95% CI, 1.82 to ‒0.26).

The investigators also carried out two case-control studies to estimate the prevalence of smoking in patients with FEP. The first study was conducted in South London. The second study — the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study — was conducted at 16 sites in Europe and Brazil.

In the South London study, 596 patients with FEP and 333 of their healthy peers were interviewed. Results showed that 70.4% of the patients with FEP and 47.6% of the control persons had ever used tobacco (P < .001).

In the EU-GEI study, the investigators interviewed 1150 patients with FEP and 1350 individuals who acted as healthy control persons about their recreational drug use and tobacco use. Roughly half of the participants underwent an Epigenome-Wide Association Study that examined epigenetics in peripheral blood.

After correcting for age, sex, and cannabis use, tobacco smoking was significantly more common in the patients with schizophrenia than in those without the disorder. There was also a strong tobacco-genetic signal in the patients with schizophrenia but not in the control group, Murray reported.

"This validated the interview data. Epigenetics provided an accurate biological measure of lifetime smoking and may be an alternative to interview," he said.

One plausible mechanism that may explain the link between psychosis and smoking tobacco comes from animal models. In one such study, administering nicotine to juvenile rats induced a persistent state of hyperactive dopamine activity in the ventral tegmental area of the brain, Murray said.

However, he cautioned that much more research needs to be done before tobacco smoking can be directly linked to psychosis.

"We have been thinking the unthinkable, which is, could one of the causes of schizophrenia-like psychosis be tobacco smoking?" Murray told Medscape Medical News.

"I've been interested for many years in the question, does cannabis induce psychosis? And I think that argument is now won. We do believe cannabis use is a risk factor for psychosis. In Europe, people tend to smoke their cannabis with tobacco. So do they get a double hit?" he asked.

However, the nature of the relationship between cigarette smoking and psychosis is still uncertain, Murray added.

"I think myself it's quite likely that smoking tobacco does turn out to be a cause, although not as significant a cause as cannabis. There is mounting evidence from animal studies that is so, but it still is early days," he said.

Medication Works

In a third presentation, A. Eden Evins, MD, Massachusetts General Hospital and Harvard Medical School, Boston, said that whether tobacco is a trigger for psychosis in susceptible individuals is almost a moot point for clinicians because it is bad for people in many ways.

Dr A. Eden Evins

Hence, there is a crucial need for effective treatments for quitting, she added.

"Smokers with serious mental illness have a 25-year mortality gap compared to the general population, but we know that these people want to quit and that long-term smoking quit rates are similar for them as for the general population," Evins said.

Smoking cessation therapy needs to include medication, she noted.

"We've seen in trial after trial that with behavioral treatment alone, people with schizophrenia have about a 4% quit rate, whereas with nicotine replacement therapy and bupropion [multiple brands], it's 10% to 12% — and with varenicline [Chantix, PF Prism CV], it's anywhere from 20% to 40%, which seems to vary with the behavioral intervention that is provided with the medication," Evins told Medscape Medical News.

A flexible or gradual approach to quitting, in which a patient who decides to quit starts taking medication for smoking cessation with a quit date up to a month after starting treatment, can be very effective for smokers with serious mental illness, she added.

Evins and colleagues reported findings in the March/April issue of the Journal of Clinical Psychopharmacology showing that varenicline, bupropion, and the nicotine patch did not increase neuropsychiatric adverse events (NPSAEs) in smokers with a psychotic disorder, anxiety, or a mood disorder.

The research, which was a secondary analysis of safety and efficacy outcomes in the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES), included a subset of 390 patients with psychosis, 792 patients with anxiety, and 2910 patients with a mood disorder.

The observed NPSAE incidence across treatments was 5.1% to 6.3% for those with a psychotic disorder, 4.6% to 8.0% for those with an anxiety disorder, and 4.6% to 6.8% for those with a mood disorder.

"I can now tell my patients that if you don't have a major psychiatric illness, you've got about a 2% chance of having a moderate to severe neuropsychiatric adverse event when you try to quit smoking, regardless of what medicine you are on," Evins said.

"And, if you have a major psychiatric illness, you have about a 6% to 7% chance of having some perturbation of your psychiatric symptoms during a smoking cessation attempt, regardless of what medicine you're on. The rate is just as high — in fact, it's identical — if you are on placebo as if you're on bupropion or varenicline," she added.

"So people do have perturbations in their symptoms when they try to quit smoking, but it doesn't seem to be the medicines. Maybe it's nicotine withdrawal, maybe it's the stress of trying to quit," she said.

The finding from EAGLES also established the superiority of varenicline over bupropion, nicotine replacement, and placebo. Bupropion and nicotine replacement therapy were better than placebo.

"Medications do help people with serious mental illness stop smoking," Evins said.

Smokers with serious mental illness "are three to six times more likely to quit when prescribed a medication. Only 4% quit without medication," she added.

Dickerson reports no relevant financial relationships. Murray reports having financial relationships with Janssen, Sunovian, Lundbeck, and Otsuka. Evins reports having financial relationships with Forum Pharmaceuticals, Pfizer, Reckitt Benckiser, and Alkermes.

Congress of the Schizophrenia International Research Society (SIRS) 2019: Presented April 11, 2019.

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