Gareth J Hollands, Máirtín S McDermott, Nicola Lindson-Hawley, Florian Vogt, Amanda Farley, Paul Aveyard

Pharmacological treatments for tobacco dependence, such as nicotine replacement therapy (NRT), have been shown to be safe and effective interventions for smoking cessation. Higher levels of adherence to these medications increase the likelihood of sustained smoking cessation, but many smokers use them at a lower dose and for less time than is optimal. It is therefore important to determine the effectiveness of interventions designed specifically to increase medication adherence. Such interventions may include further educating individuals about the value of taking medications and providing additional support to overcome problems with maintaining adherence. The primary objective of this review was to assess the effectiveness of interventions to increase adherence to medications for smoking cessation, such as NRT, bupropion, nortriptyline and varenicline (and combination regimens). This was considered in comparison to a control group, typically representing standard care. Secondary objectives were to i) assess which intervention approaches are most effective; ii) determine the impact of interventions on potential precursors of adherence, such as understanding of the treatment and efficacy perceptions; and iii) evaluate key outcomes influenced by prior adherence, principally smoking cessation. We searched the following databases using keywords and medical subject headings: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OVID SP) (1946 to July Week 3 2014), EMBASE (OVID SP) (1980 to Week 29 2014), and PsycINFO (OVID SP) (1806 to July Week 4 2014). The Cochrane Tobacco Addiction Group Specialized Register was searched on 9th July 2014. We conducted forward and backward citation searches. Randomised, cluster-randomised or quasi-randomised studies in which participants using active pharmacological treatment for smoking cessation are allocated to an intervention arm or a control arm. Eligible participants were adult (18+) smokers. Eligible interventions comprised any intervention that differed from standard care, and where the intervention content had a clear principal focus on increasing adherence to medications for tobacco dependence. Acceptable comparison groups were those that provided standard care, which depending on setting may comprise minimal support or varying degrees of behavioural support. Included studies used a measure of adherence behaviour that allowed some assessment of the degree of adherence. Two review authors searched for studies and independently extracted data for included studies. Risk of bias was assessed according to the Cochrane Handbook guidance. For continuous outcome measures, we report effect sizes as standardised mean differences (SMDs). For dichotomous outcome measures, we report effect sizes as relative risks (RRs). We obtained pooled effect sizes with 95% confidence intervals (CIs) using the fixed effects model. Our search strategy retrieved 3165 unique references and we identified 31 studies as potentially eligible for inclusion. Of these, 23 studies were excluded at full-text screening stage or identified as studies awaiting classification subject to further information. We included eight studies involving 3336 randomised participants. The interventions were all additional to standard behavioural support and typically provided further information on the rationale for, and emphasised the importance of, adherence to medication, and supported the development of strategies to overcome problems with maintaining adherence.Five studies reported on whether or not participants achieved a specified satisfactory level of adherence to medication. There was evidence that adherence interventions led to modest improvements in adherence, with a relative risk (RR) of 1.14 (95% CI, 1.02 to 1.28, P = 0.02, n = 1630). Four studies reported continuous measures of adherence to medication. Although the standardised mean difference (SMD) favoured adherence interventions, the effect was small and not statistically significant (SMD 0.07, 95% CI, -0.03 to 0.17, n = 1529). Applying the GRADE system, the quality of evidence for these results was assessed as moderate and low, respectively.There was evidence that adherence interventions led to modest improvements in rates of cessation. The relative risk for achieving abstinence was similar to that for improved adherence. It was not significant in meta-analysis of four studies providing short-term abstinence: RR = 1.07 (95% CI 0.95 to 1.21, n = 1755), but there was statistically significant evidence of improved abstinence at six months or more from a different set of four studies: RR = 1.16 (95% CI, 1.01 to 1.34, P = 0.03, n = 3049). Applying the GRADE system, the quality of evidence for these results was assessed as low for both.As interventions were similar in nature and the number of studies was low, it was not possible to investigate whether different types of intervention approaches were more effective than others. Relevant outcomes other than adherence or cessation were not reported.There was no evidence that interventions to increase adherence to medication led to any adverse events. All included studies were assessed as at high or unclear risk of bias. This was often due to a lack of clarity in reporting - meaning assessments were unclear - rather than clear evidence of failing to sufficiently safeguard against the risk of bias. There is some evidence that interventions that devote special attention to improving adherence to smoking cessation medication through providing information and facilitating problem-solving can improve adherence, though the evidence for this is not strong and is limited in both quality and quantity. There is some evidence that such interventions improve the chances of achieving abstinence but again the evidence for this is relatively weak.