Abstract: We identified 51 trials with 22,509 participants. Most recruited adults from the community using media or local advertising. People enrolled in the studies typically smoked an average of 23 cigarettes a day. We judged 18 of the studies to be at high risk of bias, but restricting the analysis only to the five studies at low or to the 28 studies at unclear risk of bias did not significantly alter results. We identified very low-certainty evidence, limited by risk of bias, inconsistency and imprecision, comparing the effect of reduction-to-quit interventions with no treatment on cessation rates (RR 1.74, 95% CI 0.90 to 3.38; I2 = 45%; 6 studies, 1599 participants). However, when comparing reduction-to-quit interventions with abrupt quitting (standard care) we found evidence that neither approach resulted in superior quit rates (RR 1. 01, 95% CI 0.87 to 1.17; I2 = 29%; 22 studies, 9219 participants). We judged this estimate to be of moderate certainty, due to imprecision. Subgroup analysis provided some evidence (P = 0.01, I2 = 77%) that reduction-to-quit interventions may result in more favourable quit rates than abrupt quitting if varenicline is used as a reduction aid. Our analysis comparing reduction using pharmacotherapy with reduction alone found low-certainty evidence, limited by inconsistency and imprecision, that reduction aided by pharmacotherapy resulted in higher quit rates (RR 1. 68, 95% CI 1.09 to 2.58; I2 = 78%; 11 studies, 8636 participants). However, a significant subgroup analysis (P < 0.001, I2 = 80% for subgroup differences) suggests that this may only be true when fast-acting NRT or varenicline are used (both moderate-certainty evidence) and not when nicotine patch, combination NRT or bupropion are used as an aid (all low- or very low-quality evidence). More evidence is likely to change the interpretation of the latter effects. Although there was some evidence from within-study comparisons that behavioural support for reduction to quit resulted in higher quit rates than self-help resources alone, the relative efficacy of various other characteristics of reduction-to-quit interventions investigated through within- and between-study comparisons did not provide any evidence that they enhanced the success of reduction-to-quit interventions. Pre-quit AEs, SAEs and nicotine withdrawal symptoms were measured variably and infrequently across studies. There was some evidence that AEs occurred more frequently in studies that compared reduction using pharmacotherapy versus no pharmacotherapy; however, the AEs reported were mild and usual symptoms associated with NRT use. There was no clear evidence that the number of people reporting SAEs, or changes in withdrawal symptoms, differed between trial arms. There is moderate-certainty evidence that neither reduction-to-quit nor abrupt quitting interventions result in superior long-term quit rates when compared with one another. Evidence comparing the efficacy of reduction-to-quit interventions with no treatment was inconclusive and of low certainty. There is also low-certainty evidence to suggest that reduction-to-quit interventions may be more effective when pharmacotherapy is used as an aid, particularly fast-acting NRT or varenicline (moderate-certainty evidence). Evidence for any adverse effects of reduction-to-quit interventions was sparse, but available data suggested no excess of pre-quit SAEs or withdrawal symptoms. We downgraded the evidence across comparisons due to risk of bias, inconsistency and imprecision. Future research should aim to match any additional components of multicomponent reduction-to-quit interventions across study arms, so that the effect of reduction can be isolated. In particular, well-conducted, adequately-powered studies should focus on investigating the most effective features of reduction-to-quit interventions to maximise cessation rates.

Plain-language summary: This review includes 51 studies of over 22,000 people who smoked tobacco. Most were adults, and people typically smoked at least 23 cigarettes a day at the start of the studies. All studies included at least one group of people who were asked to cut down their smoking and then quit tobacco smoking altogether. This group was compared to either a group who did not receive any treatment to stop smoking, a group who were asked to stop smoking all at once, or a group who were also asked to cut down their smoking in a different way. We did not include studies which asked people to cut down without quitting. Studies lasted for at least six months. The evidence is up to date to October 2018. There was not enough information available to decide whether cutting down before quitting helped more people to stop smoking than no stop-smoking treatment. However, people who were asked to stop smoking all of their cigarettes at once were not more likely to quit than people who were asked to cut down their smoking before quitting. This suggests that asking people to cut down their smoking first may be a useful way to help people to stop smoking. People who cut down their smoking while using varenicline or a fast-acting form of nicotine replacement therapy (NRT), such as gum or lozenge, may be more likely to quit smoking than people who cut down their smoking without using a medicine to help them. Giving people face-to-face support to cut down their smoking may help more people to quit than if they are provided with self-help materials to cut down by themselves. There was not enough information available to decide whether other features of the cutting-down-to-quit intervention improved people's chances of stopping smoking. We looked at whether being asked to cut down smoking before quitting resulted in negative effects, such as cigarette cravings, difficulty sleeping, low mood or irritability. Most studies did not provide information about this; more studies are therefore needed to answer this question. There is very low-quality evidence looking at whether cutting down smoking before quitting helps more people to quit smoking than no treatment. We rated the quality as very low, as there were problems with the design of studies, findings of studies were very different from one another, and not enough people took part, making it difficult to tell whether cutting down helps people to quit smoking. However, there is moderate-certainty evidence that cutting down before quitting may result in similar quit rates to quitting all at once, which suggests that cutting down may be a helpful approach. We rated this evidence as moderate because there is a chance that future studies may find that cutting down helps slightly more or slightly fewer people to quit than when people quit all at once. There is also moderate-quality evidence that people may be more likely to quit by cutting down first when they use a stop-smoking medicine like varenicline or a type of fast-acting NRT to help them. We rated this evidence as moderate certainty because there were not enough people taking part; more studies are needed.