Three first-line treatments best placebo

Three first-line medical therapies for smoking cessation—varenicline, bupropion, and nicotine replacement—were superior to placebo in people with schizophrenia spectrum disorder, a meta-analysis found.

“Given the high rates of smoking in people with schizophrenia spectrum disorders, identifying the most efficacious smoking cessation drug is important,” wrote Dan Siskind, PhD, of the University of Queensland in Brisbane, Australia, and co-authors in Lancet Psychiatry.

“In our pairwise meta-analyses, varenicline, bupropion, and nicotine replacement therapy were all superior to placebo for increasing smoking abstinence,” they noted. “However, in our network meta-analysis, varenicline was superior to bupropion for smoking abstinence.”

Pairwise meta-analyses showed the following relative risks (RR) on the primary outcome of smoking abstinence, compared with placebo:

  • Varenicline RR 3.75, 95% CI 1.96-7.19; P<0.0001.
  • Bupropion RR 3.40, 95% CI 1.58-7.34; P=0.0002.
  • Nicotine replacement RR 4.27, 95% CI 1.71-10.65; P=0.0002.

Absolute rates of smoking abstinence at intervention endpoints were low for all groups: varenicline 22% versus placebo 6%; bupropion 18% versus placebo 5%; and nicotine replacement therapy 9% versus placebo 2%.

Network meta-analysis found varenicline superior to bupropion, but no significant difference was found between varenicline and nicotine replacement therapy, or between bupropion and nicotine replacement therapy.

“The results of our study should give clinicians the confidence to offer pharmacological agents, with tailored psychosocial support, to people with psychosis,” Siskind and colleagues wrote. “Further head-to-head and combination trials of pharmacological agents for smoking cessation are required to inform clinical decision making for people with psychosis.”

In an accompanying editorial, Elaine Weiner, MD, of the University of Maryland in Baltimore, and coauthors wrote, “These results show that cessation medications are safe and effective in helping people with schizophrenia spectrum disorders to achieve short-term abstinence.

“All smokers with these disorders should be offered medication, alongside education and support, as part of standard clinical care,” they continued. “The fact that all three medication options are better than placebo allows for some discussion around patient preferences and offers alternatives if the first medication is ineffective.”

A 2014 study found that between 2004 and 2011, adjusted smoking rates for people without mental illness diagnosis declined from 19.2% to 16.5%, while among those with mental illness the decline was only from 25.3% to 24.9%. Among people with a mental illness diagnosis, those receiving mental health treatment were more likely to be abstinent (37.2% versus 33.1%).

A gap between smoking prevalence among people with schizophrenia and the general population “is compounded by the fact that people with schizophrenia have more difficulty quitting smoking, with cessation rates half of those recorded for the general population,” the researchers noted.

First-line therapy for smoking cessation includes behavioral support and one or more of the medications bupropion, varenicline, or nicotine replacement.

In their meta-analysis, Siskind and co-authors incorporated studies through September 2019, including 18 randomized controlled trials and a total of 1,437 patients that assessed the efficacy of varenicline, bupropion, or nicotine replacement therapy for smoking cessation for people with schizophrenia spectrum disorders or psychotic disorders.

Half the studies had less than 12-week duration. Mean age in the intervention groups was 42.3 and 73% were male; in controls the mean age was 42.6 and 75% were male.

Maximal doses for the three therapies were 1-2 mg/day for varenicline and 150-300 mg/day for bupropion. For nicotine replacement therapy, maximal doses were transdermal nicotine patch 14-21 mg daily, and nicotine gum 2-18 mg daily as needed.

In the network meta-analysis, varenicline was superior to bupropion (RR 2.02, 95% CI 1.04-3.93, P=0.038), but varenicline versus nicotine replacement therapy did not show a significant difference (RR 1.76, 95% CI 0.94-3.30; P=0.075). Bupropion and nicotine replacement therapy had similar efficacy (RR 0.87, 95% CI 0.41-1.85; P=0.74).

Varenicline was associated with higher rates of nausea than placebo (RR 2.32, 95% CI 1.68-3.22; P<0.0001) but no other adverse drug reactions. Bupropion had similar rates of adverse reactions to placebo.

“No drugs in our meta-analysis led to an increase in psychiatric symptoms,” the authors wrote. “Varenicline was the only agent associated with an adverse effect, nausea.”

“Although quit rates associated with the use of pharmacological agents remained low, they are still higher than quit rates usually associated with psychological interventions in people with schizophrenia spectrum disorder,” they added. “This suggests that pharmacological interventions still play an important role in aiding smoking cessation among people with schizophrenia spectrum disorders.”

A limitation of the analysis was the short-term follow-up in many studies. The authors also noted that “only 1,437 participants were able to be included. This reflects the challenges inherent in clinical trial recruitment among people with psychosis.”

  1. Three first-line medical therapies for smoking abstinence were superior to placebo in people with schizophrenia spectrum disorder, a meta-analysis found.
  2. Be aware that half the trials in the meta-analysis had less than 12-week duration.

Paul Smyth, MD, Contributing Writer, BreakingMED™

The study had no funding.

Siskind was supported by an Australian National Health and Medical Research Council Early Career Research Grant.

The editorialists declared no competing interests.


Cat ID: 57

Topic ID: 87,57,730,130,143,192,57,489,925