Combination bupropion-zonisamide facilitates rapid reduction in smoke exposure and prevents weight gain during switching to electronic nicotine delivery systems: A randomized clinical trial.

In 30 seconds

This randomized clinical trial tested whether bupropion plus zonisamide (BUP/ZON) improved smoking reduction during a switch to electronic nicotine delivery systems (ENDS), compared with bupropion alone or placebo. Adults who smoked but were not seeking cessation treatment were assigned to one of the three medication groups while using study-provided ENDS. In the modified intent-to-treat analysis, end-of-treatment exhaled carbon monoxide did not differ by treatment, but abstinence rates were higher with both active treatments than placebo: 26.7% with BUP/ZON, 25.0% with BUP, and 10.0% with placebo. Weight loss was observed with BUP/ZON, unlike the weight gain in the other groups.

Key findings

• Modified intent-to-treat analysis found no treatment differences in end-of-treatment exhaled carbon monoxide.
• Smoking abstinence rates were 26.7% with BUP/ZON, 25.0% with BUP, and 10.0% with placebo.
• Among medication-adherent participants, exhaled carbon monoxide was significantly lower with BUP/ZON than with BUP or placebo.
• Weight loss occurred with BUP/ZON, whereas weight gain occurred with BUP and placebo.

Why it matters

Switching to ENDS may be accompanied by medication strategies that support reduced cigarette exposure, but the overall analysis did not show an end-of-treatment carbon monoxide difference. The adherence-dependent signal and observed weight pattern are relevant to evaluating combined smoking-reduction and weight outcomes. These findings also underscore the need for larger trials with longer treatment duration before drawing firm conclusions.

What to keep in mind

The trial included 60 participants per group, and the clearest carbon monoxide result was in the medication-adherent per-protocol sample. The authors state that larger trials with longer treatment duration are warranted.