Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial.

BACKGROUND: Combining short-acting nicotine replacement therapy with varenicline increases smoking cessation rates compared with varenicline alone, but not all people tolerate these medications or find them helpful. We aim to investigate the therapeutic potential of an analogous combination, by evaluating the effectiveness, safety, and acceptability of combining nicotine salt e-cigarettes with cytisine, compared to nicotine salt e-cigarettes or cytisine only, on smoking abstinence at six months. METHODS: A pragmatic, community-based, investigator-blinded, randomised superiority trial design will be utilised. Eligible participants will be people who smoke daily (N = 800, 90% power) from throughout New Zealand, who are: aged ≥ 18 years, motivated to quit in the next two weeks, able to provide online consent, willing to use e-cigarettes and/or cytisine, and have daily access to a mobile phone. Recruitment will utilise multi-media advertising. Participants will be randomised (3:3:2 ratio) to 12 weeks of: 1) e-cigarettes (closed pod system, 3% nicotine salt, tobacco flavour) plus cytisine; 2) e-cigarettes alone, or 3) cytisine alone. All groups will receive a six-month, text-message-based behavioural support programme. The primary outcome is self-reported, biochemically verified, continuous abstinence at six months post-quit date. Secondary outcomes, measured at quit date, then one, three, six, and 12 months post-quit date, include self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes smoked per day, withdrawal and urge to smoke, time to (re)lapse, treatment use and compliance, treatment crossover, dual-use, use of other cessation products, change in e-cigarette products, continuation of product use, acceptability, change in health state, health-related quality of life, change in body mass index, adverse events, and cost per quitter. DISCUSSION: Pragmatic trials are of particular value as they reflect the 'real world' impact of interventions. The trial will provide some of the first evidence on the effectiveness of combining nicotine salt e-cigarettes with cytisine for smoking cessation, in a country with strong tobacco control policy. Findings will be incorporated into relevant systematic reviews, informing practice and policy. TRIAL REGISTRATION: NCT05311085 ClinicalTrials.gov. Registered 5th April, 2022.

Study of Natural Products Adverse Reactions (SONAR) in Adults with Mental Health Conditions: A Cross-Sectional Study.

INTRODUCTION: Mental illness is a leading cause of non-fatal disease burden worldwide. Natural health products (NHPs) are sought by patients with mental health conditions as a safer and more 'natural' option than conventional pharmacotherapy; however, the possible adverse events (AE) and interactions between NHPs and prescription medicines are not fully known. OBJECTIVES: The aim of this study was to determine (i) the prevalence of adult patients with mental health conditions taking prescription medications only, NHPs only, NHPs and prescription medications concurrently, or neither, (ii) which prescription medications and NHPs are most commonly used, (iii) AEs (serious and non-serious) experienced in the last 30 days for each product use group. METHODS: Mental health clinics in Alberta and Ontario, Canada, were included in an active surveillance study investigating NHP-drug interactions. On their first clinic visit, adult mental health patients were provided with a form inquiring about prescription drug use, NHP use, and any undesirable health events experienced in the last month. Healthcare professionals were also asked to report AEs. RESULTS: A total of 3079 patients were screened at 11 mental health clinics in Alberta and Ontario. In total, 620 AEs were reported in 447 patients (14.9%). The majority of adverse events were seen in patients using both NHPs and prescription medicines (58.8%), followed by patients taking only prescription medicines (37.1%), NHPs only (3.4%) and neither (0.67%). Combining NHPs and prescription medications increases the likelihood of experiencing AEs (OR 2.1; p < 0.001; 95% CI 1.7-2.6). CONCLUSIONS: Adult patients with mental health conditions who are taking both prescription medications and NHPs are more likely to report an adverse event than patients taking prescription drugs or NHPs alone. Polypharmacy increases the likelihood of an adverse event. Active surveillance is feasible and could contribute to enhanced pharmacovigilance.

Cytisine versus varenicline for smoking cessation in New Zealand indigenous Maori: a randomized controlled trial.

AIM: To determine whether cytisine was at least as effective as varenicline in supporting smoking abstinence for ≥ 6 months in New Zealand indigenous Maori or whanau (extended-family) of Maori, given the high smoking prevalence in this population. DESIGN: Pragmatic, open-label, randomized, community-based non-inferiority trial. SETTING: Bay of Plenty, Tokoroa and Lakes District Health Board regions of New Zealand. PARTICIPANTS: Adult daily smokers who identified as Maori or whanau of Maori, were motivated to quit in the next 2 weeks, were aged ≥ 18 years and were eligible for subsidized varenicline. Recruitment used multi-media advertising. INTERVENTIONS: A total of 679 people were randomly assigned (1 : 1) to receive a prescription for 12 weeks of cytisine or varenicline, plus low-intensity cessation behavioural support from the prescribing doctor and community stop-smoking services or a research assistant. Day 5 of treatment was the designated quit date. MEASUREMENTS: The primary outcome was carbon monoxide-verified continuous abstinence at 6 months, analysed as intention-to-treat (with multiple imputation for missing data). Secondary outcomes measured at 1, 3, 6 and 12 months post-quit date included: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance and acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health-related quality of life. FINDINGS: Verified continuous abstinence rates at 6 months post-quit date were 12.1% (41 of 337) for cytisine versus 7.9% (27 of 342) for varenicline [risk difference 4.29%, 95% confidence interval (CI) = -0.22 to 8.79; relative risk 1.55; 95% CI = 0.97-2.46]. Sensitivity analyses confirmed that the findings were robust. Self-reported adverse events over 6 months occurred significantly more frequently in the varenicline group (cytisine: 313 events in 111 participants; varenicline: 509 events in 138 participants, incidence rate ratio 0.56, 95% CI = 0.49-0.65, P < 0.001) compared with the cytisine group. Common adverse events were headache, nausea and difficulty sleeping. CONCLUSION: A randomized controlled trial found that cytisine was at least as effective as varenicline at supporting smoking abstinence in New Zealand indigenous Maori or whanau (extended-family) of Maori, with significantly fewer adverse events.

Hypnotherapy for smoking cessation.

BACKGROUND: Hypnotherapy is widely promoted as a method for aiding smoking cessation. It is intended to act on underlying impulses to weaken the desire to smoke, or strengthen the will to stop. OBJECTIVES: To evaluate the effect and safety of hypnotherapy for smoking cessation. SEARCH METHODS: For this update we searched the Cochrane Tobacco Addiction Group Specialized Register, and trial registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform), using the terms "smoking cessation" and "hypnotherapy" or "hypnosis", with no restrictions on language or publication date. The most recent search was performed on 18 July 2018. SELECTION CRITERIA: We considered randomized controlled trials that recruited people who smoked and implemented a hypnotherapy intervention for smoking cessation compared with no treatment, or with any other therapeutic interventions. Trials were required to report smoking cessation rates at least six months after the beginning of treatment. Study eligibility was determined by at least two review authors, independently. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data on participant characteristics, the type and duration of hypnotherapy, the nature of the control group, smoking status, method of randomization, and completeness of follow-up. These authors also independently assessed the quality of the included studies. In undertaking this work, we used standard methodological procedures expected by Cochrane.The main outcome measure was abstinence from smoking after at least six months' follow-up. We used the most rigorous definition of abstinence in each trial, and biochemically validated abstinence rates where available. Those lost to follow-up were considered to still be smoking. We summarized effects as risk ratios (RRs) and 95% confidence intervals (CIs). Where possible, we performed meta-analysis using a fixed-effect model. We also noted any adverse events reported. MAIN RESULTS: We included three new trials in this update, which brings the total to 14 included studies that compared hypnotherapy with 22 different control interventions. The studies included a total of 1926 participants. Studies were diverse and a single meta-analysis was not possible. We judged only one study to be at low risk of bias overall; we judged 10 studies to be at high risk of bias and three at unclear risk. Studies did not provide reliable evidence of a greater benefit from hypnotherapy compared with other interventions or no treatment for smoking cessation. Most individual studies did not find statistically significant differences in quit rates after six months or longer, and studies that did detect differences typically had methodological limitations.Pooling small groups of relatively comparable studies did not provide reliable evidence for a specific effect of hypnotherapy relative to controls. There was low certainty evidence, limited by imprecision and risk of bias, that showed no statistically significant difference between hypnotherapy and attention-matched behavioural treatments (RR 1.21, 95% CI 0.91 to 1.61; I2 = 36%; 6 studies, 957 participants). Results were similarly imprecise, and also limited by risk of bias, when comparing hypnotherapy to intensive behavioural interventions (not matched for contact time) (RR 0.93, 95% CI 0.47 to 1.82; I2 = 0%; 2 studies, 211 participants; very low certainty evidence). Results from one small study (40 participants) detected a statistically significant benefit of hypnotherapy compared to no intervention (RR 19.00, 95% CI 1.18 to 305.88), but this evidence was judged to be of very low certainty due to high risk of bias and imprecision. No significant differences were detected in comparisons of hypnotherapy with brief behavioural interventions (RR 0.98, 95% CI 0.57 to 1.69; I² = 0%; 2 studies, 269 participants), rapid/focused smoking (RR 1.00, 95% CI 0.43 to 2.33; I2 = 65%; 2 studies, 54 participants), and pharmacotherapies (RR 1.68, 95% CI 0.88 to 3.20; I2 = 5%; 2 studies, 197 participants). When hypnotherapy was evaluated as an adjunct to other treatments, the pooled result from five studies showed a statistically significant benefit in favour of hypnotherapy (RR 2.10, 95% CI 1.31 to 3.35; I² = 62%; 224 participants); however, this result should be interpreted with caution due to the high risk of bias across studies (four had a high risk or bias, one had an unclear risk), and substantial statistical heterogeneity.Most studies did not provide information on whether data specifically relating to adverse events were collected, and whether or not any adverse events occurred. One study that did collect such data did not find a statistically significant difference in the adverse event 'index' between hypnotherapy and relaxation. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether hypnotherapy is more effective for smoking cessation than other forms of behavioural support or unassisted quitting. If a benefit is present, current evidence suggests the benefit is small at most. There is very little evidence on whether hypnotherapy causes adverse effects, but the existing data show no evidence that it does. Further large, high-quality randomized controlled trials, and more comprehensive assessments of safety, are needed on this topic.

Suspected Hepatotoxicity With a Supercritical Carbon Dioxide Extract of Artemisia annua in Grapeseed Oil Used in New Zealand.

A case series of hepatotoxicity associated with an extract of Artemisia annua L. was identified through the New Zealand spontaneous adverse drug reaction reporting system. A. annua extract, produced using a supercritical carbon dioxide extraction method and formulated with grapeseed oil, has been marketed in New Zealand as a natural product for joint health. As of 31 January 2019, the New Zealand Pharmacovigilance Centre had received 29 reports of hepatic adverse reactions occurring in patients taking A. annua extract in grapeseed oil. The case reports were assessed for patient and adverse reaction characteristics, patterns of A. annua extract use and causality (based on the WHO-UMC system for standardized case causality assessment). Patients were aged 47 to 93 years (median 67). Time to onset of hepatotoxicity from starting A. annua extract was 7 days to approximately 12 months in the 23 reports with this information. Nineteen of these reports indicated onset within 12 weeks. A. annua extract was the sole suspect medicine in 27 reports. A few patients had possible predisposing conditions. Twenty-seven patients were reported to have recovered or improved on stopping A. annua extract. Nine patients required hospital admission. The pattern of hepatic injury varied. Jaundice, often with pruritus and dark urine, was experienced by 16 patients. There was considerable consistency across case reports from various reporters. We assessed the case reports as a series using the Bradford Hill guidelines for causal inference and concluded that there was a safety signal of a causal association between the A. annua extract and hepatotoxicity sufficient to be communicated and investigated further.

Cytisine versus varenicline for smoking cessation for Maori (the indigenous people of New Zealand) and their extended family: protocol for a randomized non-inferiority trial.

BACKGROUND AND AIMS: Cytisine, a nicotinic acetylcholine receptor partial agonist (like varenicline) found in some plants, is a low-cost, effective smoking cessation medication that may appeal to Maori [the indigenous people of New Zealand (NZ)]. The RAUORA trial aims to determine the effectiveness, safety and cost-effectiveness of cytisine (Tabex® ) versus varenicline (Champix® ) for smoking cessation in Maori and the whanau (extended family) of Maori. DESIGN: Pragmatic, community-based, open-label randomized non-inferiority trial. SETTING: Lakes District Health Board region, NZ. PARTICIPANTS: Daily smokers (n = 2140) who self-identify as Maori or whanau of Maori, and are: aged ≥ 18 years, motivated to quit smoking in the next 2 weeks, eligible for subsidized varenicline, able to provide verbal consent and have daily access to a mobile phone/internet. Recruitment uses multi-media advertising. INTERVENTION AND COMPARATOR: Participants are randomized (1 : 1 ratio) to receive a prescription for 12 weeks of cytisine tablets [following the manufacturer's dosing regimen for 25 days, then one 1.5-mg tablet every 6 hours (two per day) until 12 weeks] or varenicline tablets (following the manufacturer's dosing regimen). Both groups receive brief stop-smoking advice from the prescribing doctor and withdrawal-orientated behavioural support via community-based stop-smoking counselling services (frequency, duration and mode of delivery tailored for participants) or a research assistant (six weekly 10-15-minute calls). Participants are advised to reduce their smoking over the first 4 days of treatment, with day 5 as their designated quit-date. MEASUREMENTS: The primary outcome is carbon monoxide-verified continuous abstinence at 6 months post-quit date. Secondary outcomes at 1, 3, 6 and 12 months post-quit date include: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance, treatment acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health-related quality of life. COMMENTS: This trial compares cytisine and varenicline when used by the indigenous people of NZ and their extended family for smoking cessation.

Characteristics and practices of Traditional Chinese Medicine retail shops in London, UK: A cross-sectional study using an observational approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) is a popular form of ethnomedicine in the UK, and is accessed by Western, Chinese and other ethnic groups. The current regulatory regime does not effectively protect the public against poor-quality and unsafe TCMs. Understanding ethnopharmacological information on how TCM is promoted and practiced may help to inform initiatives aimed at ensuring the safe use of TCMs in the UK, and put laboratory-based ethnopharmacological investigations of TCMs in a broader context. AIM OF THE STUDY: This study aimed to examine the characteristics and practices of TCM retail outlets in London, UK, and to identify factors relevant to the safe use of TCM in the UK. MATERIALS AND METHODS: TCM retail outlets ('shops') in London, UK, were identified using a systematic approach. A structured questionnaire including questions on shop business type was used to recruit participant shops. Shops consenting to participate were visited within six weeks of providing consent. A piloted semi-structured questionnaire on shop characteristics was used for data collection following observation. The British National Formulary 53 was used to classify medical conditions/uses for TCMs promoted in the shops. Data were stored and analysed using MS Access 2003, MS Excel 2003 and SPSS 13. RESULTS: In total, 54 TCM shops in London were identified, of which 94% offered TCM consultations with a TCM practitioner. Detailed characteristics were described within 35/50 shops that gave consent to observing their premises. Most shops labelled and displayed over 150 Chinese Materia Medica (CMMs; crude materials, particularly herbs) for dispensing after consultations with a TCM practitioner. Medical conditions/uses and Patent Chinese Medicines (PCMs) were commonly promoted. In total, 794 occurrences of 205 different medical conditions/uses (median=32, QL=19, QU=48) were identified. These conditions/uses most commonly related to the following therapeutic systems: central nervous system (160/794, 20.2%); musculoskeletal and joint disease (133/794, 16.8%); obstetrics, gynaecology, and urinary-tract disorders (122/794, 15.4%); skin (102/794, 12.9%); gastrointestinal system (62/794, 7.8%). Specific conditions/uses that were frequently promoted included eczema (19/23 shops, 82.6%), arthritis (18/23, 78.3%), acne (17/23, 73.9%), obesity/weight loss/slimming (17/23, 73.9%) and psoriasis (17/23, 73.9%). Claimed conditions/uses included some serious medical conditions (e.g. diabetes, cancer and hypertension) and those focusing on vulnerable groups (e.g. children's diseases and pregnancy treatments). CONCLUSIONS: TCM shops in London, UK, typically displayed names of a wide range of medical conditions/uses for TCMs using readily understandable medical terms, implying TCM can be used to prevent or treat these conditions. However, many of these advertisements did not comply with UK regulations on medical claims for herbal medicines. Future studies should explore how these advertisements influence consumers' decisions to access TCM in the UK, practices of TCM shop staff towards the supply of TCMs in the UK, and what are the health implications at the individual and population levels.

Cytisine versus nicotine for smoking cessation.

BACKGROUND: Placebo-controlled trials indicate that cytisine, a partial agonist that binds the nicotinic acetylcholine receptor and is used for smoking cessation, almost doubles the chances of quitting at 6 months. We investigated whether cytisine was at least as effective as nicotine-replacement therapy in helping smokers to quit. METHODS: We conducted a pragmatic, open-label, noninferiority trial in New Zealand in which 1310 adult daily smokers who were motivated to quit and called the national quitline were randomly assigned in a 1:1 ratio to receive cytisine for 25 days or nicotine-replacement therapy for 8 weeks. Cytisine was provided by mail, free of charge, and nicotine-replacement therapy was provided through vouchers for low-cost patches along with gum or lozenges. Low-intensity, telephone-delivered behavioral support was provided to both groups through the quitline. The primary outcome was self-reported continuous abstinence at 1 month. RESULTS: At 1 month, continuous abstinence from smoking was reported for 40% of participants receiving cytisine (264 of 655) and 31% of participants receiving nicotine-replacement therapy (203 of 655), for a difference of 9.3 percentage points (95% confidence interval, 4.2 to 14.5). The effectiveness of cytisine for continuous abstinence was superior to that of nicotine-replacement therapy at 1 week, 2 months, and 6 months. In a prespecified subgroup analysis of the primary outcome, cytisine was superior to nicotine-replacement therapy among women and noninferior among men. Self-reported adverse events over 6 months occurred more frequently in the cytisine group (288 events among 204 participants) than in the group receiving nicotine-replacement therapy (174 events among 134 participants); adverse events were primarily nausea and vomiting and sleep disorders. CONCLUSIONS: When combined with brief behavioral support, cytisine was found to be superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12610000590066.).

Medicinal plants used for menstrual disorders in Latin America, the Caribbean, sub-Saharan Africa, South and Southeast Asia and their uterine properties: a review.

ETHNOPHARMACOLOGICAL RELEVANCE: Menstrual disorders are generally not perceived as major health concerns by global health organizations, despite being disruptive to women׳s daily activities, particularly when access to sanitary facilities or analgesics is limited. Improving menstrual health requires access to safe and effective medication, but many women in Latin America, Africa or Asia prefer traditional medicine above modern remedies (such as contraceptives), as they can cause physical symptoms associated with fertility loss. Many medicinal plants are used for menstrual disorders, but few have been examined for their pharmacological activities related to traditional uses. Plants that have a smooth muscle-relaxant effect could ease menstrual cramps, but there are indications that dysmenorrhea in low-income countries is commonly treated with emmenagogues. This review aims to assess the most salient plants used to treat menstrual morbidity in Latin America and the Caribbean, sub-Saharan Africa, South and Southeast Asia, their uterine properties and adverse effects. To test whether plants used for painful menstruation could have uterine contracting properties, we recorded whether these species were also used to ease birth, induce menstruation, abortion or expel the afterbirth, as these suggest spasmogenic activities. MATERIALS AND METHODS: We reviewed the literature documenting traditional plant use in the study area for dysmenorrhea, regulating or inducing menstruation, uterine cleansing, uterine fibroids, expelling the placenta and lochia and for easing childbirth. Thirty genera (59 species) used in at least two continents or frequently throughout one continent, where shortlisted from the 90 most salient plant species emerging from our literature review. Using Medline, we searched for pharmacological properties and/or mechanisms of action relevant to their traditional uses of the shortlisted species. We searched VigiBase™, the WHO global individual case safety report database, on reported adverse drug reactions associated with these species. RESULTS: More than 2000 plant species are used for menstrual disorders in the study area. The most salient uses are to treat painful menstruation, induce or regulate menses, and induce abortion. Around half (29) of the 59 most salient species have been tested for their pharmacological effects, of which 48% act as uterine spasmolytics and 31% as uterine spasmogenics. Several frequently used species contain toxic constituents, which may put women and their unborn children at serious risk. VigiBase(TM) listed adverse drug reactions for 18 of these species, but few reports came from the study area. CONCLUSIONS: Research into the risks and benefits of medicinal plants for menstrual complaints should be given a higher priority in reproductive health programs that respect traditional knowledge and practices. Increased data collection is needed on adverse drug reactions among women using herbal medicines for reproductive health, especially in countries with limited reproductive health facilities.

Pharmacists' views on and experiences with bowel cancer screening kits in Auckland, New Zealand.

OBJECTIVES: To explore the views of New Zealand pharmacists on bowel cancer screening, particularly with regards to faecal occult blood testing (FOBT) kits, self-perceived knowledge on FOBT kits and barriers, motivators and experiences with selling and counselling consumers with respect to FOBT kits. METHODS: Semi-structured interviews were conducted face to face or by telephone with 20 community pharmacists in the Auckland region. Interviews were recorded and transcribed verbatim and data were coded and analysed using NVivo software to identify key themes. KEY FINDINGS: Participant pharmacists believed that they were well placed to provide advice on FOBT kits to consumers. Barriers to selling the kits included cost and perceived lack of test sensitivity of the kits, poor consumer demand, pharmacists' lack of training and information, and a belief that selling FOBT kits was outside the pharmacists' scope of practice. Motivators to selling the kits included customer convenience, ease of use, confidence in the kits and embracing new roles for pharmacists. Pharmacists were concerned that use of the kits may increase the burden on the public health system through customer anxiety over test results; however, they agreed that there was a need for bowel cancer screening and awareness and that people concerned about bowel cancer should make visiting their general practitioner a priority. CONCLUSIONS: Pharmacists' views were mixed. Pharmacists' training and competence with respect to the provision of bowel cancer kits, and how a bowel cancer screening service can be developed to optimise public health outcomes, need to be addressed.

A national census of medicines use: a 24-hour snapshot of Australians aged 50 years and older.

OBJECTIVE: To explore the current use of conventional and complementary medicines in Australians aged ≥ 50 years. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional postal survey sent to a random sample of 4500 Australians aged ≥ 50 years between June 2009 and February 2010. MAIN OUTCOME MEASURES: Prevalence of medicines use, reasons for medicines use and sources of medicines. RESULTS: Response rate was 37.3%. Medicines use was very common; 87.1% of participants took one or more medicines and 43.3% took five or more in the previous 24 hours. Complementary medicines were used by 46.3% of participants, 87.4% of whom used both conventional and complementary medicines. The most commonly used medicines were antihypertensive agents (43.2% of participants), natural marine and animal products including fish oil and glucosamine (32.4%) and lipid-lowering agents (30.4%). Doctors recommended 79.3% of all medicines and 93.0% of conventional medicines. Pharmacists commonly recommended occasional medicines (ie, as needed), while friends, family and media most often influenced use of complementary medicines. CONCLUSIONS: The use of multiple medicines is common and higher than reported in the 1995 National Health Survey. Today, much medicines use is to prevent future disease by influencing risk factors. High levels of polypharmacy highlight the need to support the safe and effective use of medicines in the community. Although doctors recommend or prescribe most medicines, self-directed medication use is common. This highlights the need for consumer access to accurate information and strategies to improve health literacy about medicines.

Study protocol for a non-inferiority trial of cytisine versus nicotine replacement therapy in people motivated to stop smoking.

BACKGROUND: Smokers need effective support to maximise the chances of successful quit attempts. Current smoking cessation medications, such as nicotine replacement therapy (NRT), bupropion, nortriptyline or varenicline, have been shown to be effective in clinical trials but are underused by smokers attempting to quit due to adverse effects, contraindications, low acceptability and/or high cost. Cytisine is a low-cost, plant-based alkaloid that has been sold as a smoking cessation aid in Eastern Europe for 50 years. A systematic review of trial evidence suggests that cytisine has a positive impact on both short- and long-term abstinence rates compared to placebo. However, the quality of the evidence is poor and insufficient for licensing purposes in many Western countries. A large, well-conducted placebo-controlled trial (n = 740) of cytisine for smoking cessation has recently been published and confirms the findings of earlier studies, with 12-month continuous abstinence rates of 8.4% in the cytisine group compared to 2.4% in the placebo group (Relative risk = 3.4, 95% confidence intervals 1.7-7.1). No research has yet been undertaken to determine the effectiveness of cytisine relative to that of NRT. METHODS/DESIGN: A single-blind, randomised controlled, non-inferiority trial has been designed to determine whether cytisine is at least as effective as NRT in assisting smokers to remain abstinent for at least one month. Participants (n = 1,310) will be recruited through the national telephone-based Quitline service in New Zealand and randomised to receive a standard 25-day course of cytisine tablets (Tabex®) or usual care (eight weeks of NRT patch and/or gum or lozenge). Participants in both study arms will also receive a behavioural support programme comprising an average of three follow-up telephone calls delivered over an eight-week period by Quitline. The primary outcome is continuous abstinence from smoking at one month, defined as not smoking more than five cigarettes since quit date. Outcome data will also be collected at one week, two months and six months post-quit date. DISCUSSION: Cytisine appears to be effective compared with placebo, and given its (current) relative low cost may be an acceptable smoking cessation treatment for smokers, particularly those in low- and middle-income countries. Cytisine's 'natural' product status may also increase its acceptability and use among certain groups of smokers, such as indigenous people, smokers in countries where the use of natural medicines is widespread (e.g. China, India), and in those people who do not want to use NRT or anti-depressants to help them quit smoking. However it is important to ascertain the effectiveness of cytisine compared with that of existing cessation treatments. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12610000590066).

A pilot randomised, open, uncontrolled, clinical study of two dosages of St John's wort (Hypericum perforatum) herb extract (LI-160) as an aid to motivational/behavioural support in smoking cessation.

There is an association between smoking and depression, yet the herbal antidepressant St John's wort (Hypericum perforatum L.; SJW) herb extract has not previously been investigated as an aid in smoking cessation. In this open, uncontrolled, pilot study, 28 smokers of 10 or more cigarettes per day for at least one year were randomised to receive SJW herb extract (LI-160) 300 mg once or twice daily taken for one week before and continued for 3 months after a target quit date. In addition, all participants received motivational/behavioural support from a trained pharmacist. At 3 months, the point prevalence and continuous abstinence rates were both 18%, and at 12 months were 0%. Fifteen participants (54%) reported 23 adverse events up to the end of the 3-month follow-up period. There was no statistically significant difference in the frequency of adverse events for participants taking SJW once or twice daily (p > 0.05). Most adverse events were mild, transient and non-serious. This preliminary study has not provided convincing evidence that a SJW herb extract plus individual motivational/behavioural support is likely to be effective as an aid in smoking cessation. However, it may be premature to rule out a possible effect on the basis of a single, uncontrolled pilot study, and other approaches involving SJW extract may warrant investigation.