Smoking is one of the leading preventable causes of illness, disability and premature death worldwide. The global mortality attributable to smoking is 5 million people annually and increasing.

In the general population levels of smoking are on the decline, however this pattern is not seen in those diagnosed with psychiatric illness. The prevalence of smoking amongst adults will severe mental illness is approximately 53%.

Pharmacological treatments exist to help individuals to quit smoking. The main drug treatments are:

• Bupropion
• Varenicline
• Nicotine replacement therapy (NRT)

Each of these treatments show beneficial effects on smoking cessation alone, or in combination. Furthermore, they are associated with low risk of side effects and demonstrate overall cost-effectiveness. Despite a substantial evidence base for their effectiveness in the general population, these treatments are under-utilised in people with serious mental illness; possibly due to concerns around their tolerability.

In a recent study published in Addiction, the authors set out to examine the efficacy and tolerability of adjunctive pharmacotherapies for smoking cessation in adults suffering from serious mental illness. Pharmacotherapies included bupropion, varenicline and NRT delivered alone or in combination.

Methods

The authors conducted a comprehensive literature search (Embase, Medline, PsychINFO and the Cochrane Central Register of Controlled Trials from database inception to 1 December 2014) for randomised controlled trials (RCTs).

In order to be eligible for inclusion RCTs had to assess adult participants with any form of serious mental illness (a non-organic disorder with psychotic features that results in disability), compare pharmacotherapies to one another or a placebo and contribute data to the efficacy or tolerability outcome. Efficacy was a sustained smoking cessation outcome, i.e. abstinence for 6 months or more, however if 6 month data was not available the longest reported time-point was used. The tolerability outcome was the rate of discontinuation from the trial due to any adverse event.

The authors conducted a network meta-analysis which allows for direct comparisons of treatments as well as indirect comparisons based around a common comparator.

Results

Following initial searches, 17 study reports were included; containing a total of 14 RCTs. It’s worth noting that the results of the SCIMITAR RCT, which used tailored interventions including pharmacotherapy, were not included in this review and meta-analysis, as it was published too recently (2015) to be included.

The quality of all the RCTs was rated as very low, with most studies providing no information about randomisation or allocation concealment.

Efficacy

Nine trials contributed to the efficacy meta-analysis, with a total of 356 participants.

• Both bupropion (OR = 4.51, 95% CrI = 1.45 to 14.04) and varenicline (OR = 5.17, 95% CrI* = 1.78 to 15.06) were significantly more effective than placebo for smoking cessation in individuals with a serious mental illness.
• However, there was no advantage of one treatment over the other (OR = 1.15, 95% CrI = 0.24 to 5.45).

* Note: CrI stands for Credible Interval, which is different from a Confidence Interval. Find out more here.

Tolerability

There were no significant differences between treatments in terms of their acceptability:

• Bupropion vs placebo (OR = 1.07, 95% CrI = 0.34 to 3.35)
• Varenicline vs placebo (OR = 1.30, 95% CrI = 0.50 to 3.37)
• Varenicline vs bupropion (OR = 1.21, 95% CrI = 0.28 to 5.19)

Discussion

Both bupropion and varenicline are effective and tolerable pharmacotherapies for smoking cessation in adults with a serious mental illness. Whilst both were superior to placebo, they did not differ from each other. Furthermore, both treatments were considered acceptable and did not lead to increased dropout rates. These findings suggest that more focus should be given to psychopharmacological treatments for smoking cessation in those with a serious mental illness.

There were several limitations to this study:

• First, there were a small number of RCTs which were included with few participants; in fact two studies only enrolled five participants. Therefore, more studies are required to ensure effect estimates are robust and reliable
• Second, there was not enough evidence to draw any conclusions about the efficacy or tolerability of NRT against placebo
• Finally, the majority of RCTs were conducted in individuals with schizophrenia or schizoaffective disorder. Therefore, it is difficult to translate the findings past these disorders; although 3 studies (with 70 participants) were conducted in bipolar affective disorder.

An informative commentary on the published paper sums up the current research well by stating:

Individuals with serious mental illness want to quit and can quit with evidence-based cessation medications and counselling support…The conclusion that bupropion and varenicline are efficacious medications is an important clinical finding.

Nevertheless, large scale focused RCTs are required to build upon this promising finding.

Links

Primary paper

Roberts E, Eden Evins A, McNeill A, Robson D. (2016) Efficacy and tolerability of pharmacotherapy for smoking cessation in adults with serious mental illness: a systematic review and network meta-analysis. Addiction, 11: 599–612. doi: 10.1111/add.13236. [Abstract]

Other references

McClave AK, McKnight-Eily LR, Davis SP, Dube SR. (2010) Smoking characteristics of adults with selected lifetime mental illnesses: results from the 2007 National Health Interview Survey. American Journal of Public Health, 100, 2464-72.

Prochaska JJ. (2016) Commentary on Roberts et al. (2016): Bupropion and varenicline are efficacious and well-tolerated cessation medications for smokers with serious mental illness. Addiction, 111, 613-4. [Abstract]

Adams S. (2015) Smoking cessation for people with severe mental illness (the SCIMITAR RCT). Mental Elf, 13 Jul 2015.

Photo credits

• mason bryant CC BY 2.0
• anis eka CC BY 2.0