People living with severe mental illness (SMI) die 15 to 20 years earlier than the rest of the population, and cigarettes play a large part in that gap. So the question of how to quit smoking with severe mental illness is a matter of life and death, not a footnote. A new review in BMJ Medicine by Bekkering and colleagues now gives doctors a much firmer guide. After pooling 74 trials with 11,023 participants, the researchers found that varenicline came out on top.

A life expectancy gap that smoking helps to drive

SMI covers long term, complex conditions such as schizophrenia, bipolar disorder and psychosis. They bring serious challenges for social, emotional and physical health. Most of the early deaths come from cardiovascular disease and cancer, and both are strongly linked to smoking.

The smoking figures are stark. Around 40% of people with SMI smoke tobacco. They also tend to start younger and smoke more heavily than the general population.

Quitting matters for the mind as well as the body. Research has linked stopping smoking with lower depression, anxiety and stress. Until now there was little evidence comparing the different ways of helping people with SMI to stop. Many who want to quit smoking with severe mental illness without a clear idea of which option to try first.

How the researchers compared the treatments

The team searched several databases and trial registries up to September 2024. The aim was to learn what helps people quit smoking with severe mental illness. They looked for randomised controlled trials in adults with schizophrenia, bipolar disorder, major depressive disorder or post traumatic stress disorder (PTSD). Each trial had to test a stop smoking treatment against another treatment, a placebo, standard care or no treatment.

Two reviewers screened every paper independently. The team grouped the treatments into three arms: medicines, support without medicines, and a combination of both. A network meta analysis let them compare treatments that no single trial had tested head to head. That approach gave the review real reach on smoking cessation for severe mental illness.

Participants had an average age of 46 and smoked a mean of 20 cigarettes a day. Around 65% were men. Treatment lasted about 12.5 weeks on average, with follow up for around 22 weeks afterwards. Every trial, though, took place in a high income country.

Varenicline leads on quit rates

For short term quitting, 27 trials went into the analysis. Three medicines beat placebo or minimal care, with moderate or high certainty evidence:

• Varenicline: odds ratio (OR) 3.89, or 17 more quitters per 100 adults
• Nicotine replacement therapy (NRT): OR 2.30, or 8 more quitters per 100 adults
• Bupropion: OR 2.01, or 7 more quitters per 100 adults

Varenicline also outperformed its rivals. The comparison favoured it over NRT (OR 1.69) and over bupropion (OR 1.92).

The long term results, based on 28 trials, told a similar story for people who quit smoking with severe mental illness. Varenicline again led with an OR of 2.84, and bupropion followed at 1.89. Both rested on moderate or high certainty evidence. A combination of medicine and support without medicines looked promising at 2.09, but the certainty there was low.

Just as important, the medicines did not appear to worsen mental health. Among trials reporting depressive symptoms and psychopathology, varenicline, bupropion and NRT made little or no difference compared with placebo or minimal care. For anyone hoping to quit smoking with severe mental illness, that is welcome news.

Safety questions and gaps that remain

However, the reassurance has limits. Across 11 trials reporting serious adverse events, every intervention showed a small increase in risk compared with placebo or minimal care, though the evidence was very uncertain. For dropouts, quality of life and weight gain, the analyses showed little to no difference, but the certainty was low.

The review has other limits. Over a third of participants came from the EAGLES trials, which enrolled around 4,166 people with psychiatric disorders. That makes the findings more dependent on how those trials ran. Of the 74 studies, 72 carried a risk of bias in at least one area, mainly because of unclear reporting of randomisation and a lack of masking.

Only one study looked at electronic cigarettes, so the evidence on whether they help people quit smoking with severe mental illness is too thin to judge. Support without medicines also varied widely in content, intensity and setting. Nobody can yet say which type works best.

What this means for people who want to quit smoking with severe mental illness

Earlier research by Taylor and colleagues found that varenicline is less likely to be prescribed for people with SMI than NRT. Some clinicians stay cautious because of the psychiatric side effects listed in NICE guidelines. The new review found little or no effect on depression or overall psychiatric symptoms, which should offer some comfort. Serious adverse events remain uncertain.

For people trying to quit smoking with severe mental illness, US guidance from SAMHSA recommends combining medicine with behavioural support. The new analysis is unsure how much extra benefit the pairing brings, but that is not proof that support fails. A Cochrane review found that counselling and economic incentives consistently helped people stop smoking. A secondary analysis of the EAGLES trial also pointed to varenicline plus counselling for people with major depressive disorder. So clinicians can offer both, following each person’s preferences and the help available, and can offer medicine alone to anyone who declines support.

Honest conversation matters too. Clinicians should be open about what is still unknown and make decisions together with patients.

Behind the numbers sits a simple principle. People with SMI should have the same access to disease prevention, and the same chance of good physical health, as everyone else. This review shows that effective options exist and that varenicline deserves a place in the conversation. Smoking cessation for severe mental illness still needs larger trials on combined treatments, and on outcomes such as serious adverse events, quality of life and weight.

Source: dbrecoveryresources