Second-line Pharmacotherapy Research Articles

Disseminating cognitive behavioural therapy (CBT) for insomnia at scale: capitalising on the potential of digital CBT to deliver clinical guideline care.

Cognitive behavioural therapy (CBT) is the recommended first-line treatment for insomnia. However, guideline care is very seldom available and most patients receive no treatment, or less effective second-line pharmacotherapy or sleep hygiene, neither of which are evidence-based for chronic insomnia. The primary challenge for CBT has been supply. There are not enough therapists to meet the enormous demand. We must accelerate clinician training, but this approach can never be sufficient, even with abbreviated, efficient therapies. Fortunately, however, the treatment landscape has also changed dramatically. Fully-automated digital CBT (dCBT) has emerged as a safe, effective, and scalable treatment delivery format. dCBT is software only, so it can be disseminated as readily and widely as sleep medication. Moreover, dCBT can be integrated into services. Just as medications can be delivered through health professionals and health systems, approved dCBT programmes can be the same. However, an ecosystem of psychologically-based care should not necessitate a medical prescription model. Our proposed stepped care framework, comprises both population health and clinical health service initiatives, enabling universal access to guideline care for insomnia. The diverse ways in which CBT may be delivered (in-person, face-to-face, using telehealth, group therapy, digitally) can operate congruently and efficiently to optimise treatment for people at all levels of complexity and need. With safe and clinically effective dCBT products now set to become established as treatments, clearly differentiated from wellness apps, there is potential to rapidly transform insomnia services and, for the first time, to deliver clinical guideline care at international scale.

Expert consensus on the diagnosis and treatment of adult attention deficit hyperactivity disorder in China (2023 Edition)

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in school-age children, with 30%-50% persisting into adulthood. In addition, adult ADHD patients have more comorbidities, are more difficult to identify, and have a wider range of impairments on individual function, thereby leading to more serious adverse effects on medical care, economy and society. This consensus establishes the diagnose of adult ADHD based on the 11th edition of International Classification of Diseases (ICD-11), determines the treatment plans based on the etiology and pathogenesis of the disease, recommends psycho-stimulants as the first-line pharmacotherapy for adult ADHD and selective noradrenalin reuptake inhibitors (NARIs) as the second-line pharmacotherapy to reduce the core symptoms, and combines non-pharmacological treatments, such as cognitive behavioral therapy, health education and lifestyle training, aiming to improve patients' functioning and quality of life to the utmost.

Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-Line Drugs: A Nation-Wide Population-Based Comparative Safety Study.

To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidylpeptidase-4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study. A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial. Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17). Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.

Sodium-Glucose Cotransporter-2 Inhibitors-from the Treatment of Diabetes to Therapy of Chronic Heart Failure.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are currently the second-line pharmacotherapy in type 2 diabetes, particularly through their effectiveness in reducing glycemia, but also due to their cardioprotective and nephroprotective effects. In light of surprisingly satisfactory results from large, randomized trials on gliflozins, SGLT2 received the highest recommendation (Class IA) with the highest level of evidence (A) in the treatment algorithm for HF with reduced LVEF in recent ESC HF guidelines. This great breakthrough in the treatment of HF is due to different mechanisms of action of gliflozins that are reported to be able to change the natural course of HF by reducing the risk of both hospitalization and death. They are recommended regardless of the patient’s diabetes status. This review summarizes the up-to-date literature on their beneficial and pleiotropic impact on the cardiovascular system.

The Role of Non-statin Lipid-Lowering Medications in Youth with Hypercholesterolemia.

Lifestyle modification is additive to lipid-lowering medications in the treatment of heterozygous familial hypercholesterolemia (HeFH), which does not respond sufficiently to statin therapy. While both are also important in homozygous familial hypercholesterolemia (HoFH), additional measures such as apheresis may be needed. The purpose of this review is to identify non-statin medications to lower cholesterol that are available for children and adolescents as adjunctive therapy. Ezetimibe is commonly used as second-line pharmacotherapy for treatment of HeFH and HoFH. Colesevelam, a bile acid sequestrant, may be considered for adjunct therapy. Since 2015, the PCSK9 inhibitor evolocumab has been available for adolescents, and its FDA approval has now expanded to age 10years. The ANGPTL3 inhibitor evinacumab has been approved for children age 12years and older. A clinical trial for lomitapide is in progress. Approvals for PCSK9 and ANGPTL3 inhibitors have expanded opportunities for children and adolescents with HeFH and HoFH to achieve lower LDL-C levels.

Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment.

Osteoarthritis (OA) can be defined as the result of pathological processes of various etiologies leading to damage to the articular structures. Although the mechanism of degenerative changes has become better understood due to the plethora of biochemical and genetic studies, the drug that could stop the degenerative cascade is still unknown. All available forms of OA therapy are based on symptomatic treatment. According to actual guidelines, comprehensive treatment of OA should always include a combination of various therapeutic options aimed at common goals, which are pain relief in the first place, and then the improvement of function. Local treatment has become more common practice, which takes place between rehabilitation and pharmacological treatment in the hierarchy of procedures. Only in the case of no improvement and the presence of advanced lesions visible in imaging tests, should surgery be considered. Currently, an increasing number of studies are being published suggesting that intra-articular injections may be as effective or even more effective than non-steroidal anti-inflammatory drugs (NSAIDs) and result in fewer systemic adverse events. The most commonly used preparations are hyaluronic acid (HA), glucocorticosteroids (GS), and also platelet-rich plasma (PRP) in recent years. This review aims to present the mechanism of action and clinical effectiveness of different pharmacological options in relieving pain and improving functions in OA as well as the emerging approach in intra-articular treatment with PRP.

Positioning Infliximab and Vedolizumab in the Treatment of Moderate-to-Severe Ulcerative Colitis

Positioning Infliximab and Vedolizumab in the Treatment of Moderate-to-Severe Ulcerative Colitis

Management of heart failure with reduced ejection fraction in 2021: an update for GPs.

In February 2021, the National Institute for Health and Care Excellence (NICE) approved the use of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i) for patients with or without diabetes and with a left ventricular ejection fraction (LVEF) of <40%.1 This article provides some practical guidance for GPs on implementing the recommendation. Until recently, three groups of drugs were recommended by NICE as standard therapy to improve symptoms and prognosis in heart failure with reduced ejection fraction (HFrEF). The aspiration is for patients to receive them at the maximal tolerated doses (Table 1). The groups are: angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin-neprilysin inhibitors (ARNI); beta-blockers (BB); and — for patients remaining symptomatic — mineralocorticoid receptor antagonists (MRA). View this table: Table 1. First- and second-line pharmacotherapy groups (’the four pillars’) known to reduce mortality in HFrEF and approved by NICEa In patients with persistent or worsening symptoms whose LVEF is <35%, any ACEI/ARB should be replaced with sacubitril–valsartan (Entresto®), the current sole licensed member of ARNI, as both symptoms and prognosis are improved.2 Chronic heart failure still carries a poor prognosis, worse than some cancers, with a mortality of 42% at 5 years after the diagnosis in the UK.3 In part this reflects incomplete optimisation of existing therapies. GPs have a major role to play in spotting the need for medicines optimisation (Table 1), considering non-pharmacological interventions, and liaising with the community heart failure nurse and cardiac rehabilitation teams. In the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial, addition of dapagliflozin reduced the composite cardiovascular endpoint (hospitalisation for heart failure, urgent outpatient diuretic, therapy, or cardiovascular death) by 26% with a Number …

Issue Highlights

Issue Highlights

Proceedings of an emergency medical team (paramedics) with a patient in anaphylaxis

Introduction: Anaphylactic shock is an acute allergic body reaction to allergens. This condition threatens the patient's life and health. Anaphylaxis can be caused by intolerance to many nutrients, medications or hymenoptera stings.Aim of the manuscript: The aim of the manuscript was to determine the pattern of proceedings of emergency medical teams with patients in anaphylactic shock.Material and methods: The individual case method of a patient stung by a Hymenoptera insect, for whom a medical rescue team was dispatched, was used. The research material was obtained thanks to the analysis of medical rescue operations and dispatch orders.Results: The analysis of medical records of the injured person depicted an appropriate algorithm of proceedings with a patient in anaphylactic shock. In anaphylaxis, it is important to gather information as soon as possible, make an accurate and prompt diagnosis, and provide immediate pharmacotherapy. In this case, the first-line drug is Adrenaline, which prevents the release of histamine and reverses the effects of shock. Further treatment requires oxygen, fluids and second-line pharmacotherapy. Conclusions: The emergency medical team followed the applicable algorithms and current knowledge. It implemented appropriate medical rescue operations, thanks to which the condition of the injured was stabilized. The first step is to stop the exposure to the allergen.

Myopathy secondary to empagliflozin therapy in type 2 diabetes.

SummarySodium/glucose co-transporter 2 (SGLT2) inhibitors are novel oral hypoglycaemic agents that are increasingly used in the management of type 2 diabetes mellitus (T2DM). They are now recommended as second-line pharmacotherapy (in conjunction with metformin) in patients with type 2 diabetes and established atherosclerotic heart disease, heart failure or chronic kidney disease due to their favourable effects on cardiovascular and renal outcomes. We report a case of a 69-year-old man who developed muscle pain, weakness and wasting after commencing the SGLT2 inhibitor empagliflozin. This persisted for 1 year before he underwent resistance testing, which confirmed muscle weakness. His symptoms resolved within weeks of ceasing empagliflozin, with improvement in muscle strength on clinical assessment and resistance testing and reversal of MRI changes. No other cause of myopathy was identified clinically, on biochemical assessment or imaging, suggesting that empagliflozin was the cause of his myopathy.Learning points:Empagliflozin, a commonly used SGLT2 inhibitor, was associated with myopathy.A high degree of suspicion is required to diagnose drug-induced myopathy, with a temporal relationship between starting the medication and symptom onset being the main indicator.Recognition of drug-induced myopathy is essential, as discontinuation of the offending drug typically improves symptoms.

&lt;p&gt;Burden of diabetes mellitus in patients with acromegaly treated with second-line pharmacotherapy in Spain&lt;/p&gt;

ObjectiveTo evaluate the burden of diabetes mellitus (DM) in adult patients with acromegaly treated with second-line pharmacotherapy, from the perspective of the Spanish National Health System (NHS).MethodsA Markov model was developed including three states: normal glucose metabolism, DM and death. The evolution of a hypothetical cohort of acromegaly patients requiring second-line pharmacological treatment (pegvisomant or pasireotide) after first generation somatostatin analogues therapy was analyzed. Direct healthcare costs regarding acromegaly management, diabetes management and drugs costs were obtained from Spanish sources. Transition probabilities between health states were obtained from published studies. Deterministic and probabilistic sensitivity analyses were undertaken.ResultsCompared to pasireotide, pegvisomant increased the likelihood of glucose normalization and reduced the likelihood of DM. Consequently, in a cohort of 1,000 patients with acromegaly, treatment with pegvisomant compared to pasireotide would prevent 243, 413 and 453 cases of DM after 1, 2 and 5 years, respectively, and would reduce mortality by 0.1% after 5 years of treatment. This would result in 1 million euros savings for the NHS in 5 years. These health benefits would be obtained with savings of €1,512, €3,422 and €10,162 per patient treated with pegvisomant, after 1, 2 and 5 years, respectively. After 5 years of treatment, the probability that pegvisomant generated savings versus pasireotide would be 65.3%.ConclusionThe favorable effects of pegvisomant on glucose metabolism would allow a considerable number of cases of DM to be avoided compared to pasireotide, resulting in savings for the NHS in Spain.

Comparative survival benefit of currently licensed second or third line treatments for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) negative advanced or metastatic non-small cell lung cancer: a systematic review and secondary analysis of trials

BackgroundA review of therapies for advanced cancers licenced by the EMA between 2009 and 2013 concluded that for more than half of these drugs there was little evidence of overall survival or quality of life benefit. Recent years have witnessed a growing number of licensed second-line pharmacotherapies for advanced/metastatic non-small cell lung cancer (NSCLC). With the aim of gauging patient survival benefit, we conducted a systematic review of randomised controlled trials (RCT) and compared survival outcomes from available licensed treatments for patients with advanced/metastatic NSCLC.MethodsRCTs of second/third line treatments in participants with advanced/metastatic NSCLC and negative/low expression of Anaplastic Lymphoma Kinase (ALK) and of Epidermal Growth Factor Receptor (EGFR) were included. We searched electronic databases (MEDLINE; EMBASE; Web of Science) from January, 2000 up to July, 2017. Two or more independent reviewers screened bibliographic records, extracted data, and assessed risk of bias of studies. Published Kaplan Meier plots for OS and PFS along with restricted-mean-survival methods and parametric modelling were used to estimate the survival outcomes as mean number of months of survival. Network meta-analysis was undertaken to rank interventions and to make indirect comparisons.ResultsWe included 11 RCTs with data for 7581 participants that compared nine different drugs. In studies of patients regardless of histology groups, targeted drugs (ramucirumab and nintedanib) yielded small overall survival gains of < 2.5 months over docetaxel, erlotinib provided no benefit, while immunotherapies (atezolizumab and pembrolizumab) delivered 5 to 6 months gain. Studies with patients stratified by histology confirmed the apparent superiority of immunotherapy (nivolumab and atezolizumab) over targeted treatments (ramucirumab, nintedanib, afatinib) providing between about 4 to 8 months OS gain over docetaxel. In network analysis immunotherapies consistently ranked higher than alternatives irrespective of population histology and outcome measure.ConclusionOur review indicates that nivolumab, pembrolizumab and atezolizumab provide superior survival benefits compared to other licensed drugs for late stage NSCLC. Patient gains from these immunotherapies are substantial compared to the expected average survival with chemotherapy (docetaxel) of < 1 year for people with squamous histology and about 1.25 year for those with non-squamous histology.

Cardiovascular risk profile in individuals initiating treatment for overactive bladder – Challenges and learnings for comparative analysis using linked claims and electronic medical record databases

For managing overactive bladder (OAB), mirabegron, a β3 adrenergic receptor agonist, is typically used as second-line pharmacotherapy after antimuscarinics. Therefore, patients initiating treatment with mirabegron and antimuscarinics may differ, potentially impacting associated clinical outcomes. When using observational data to evaluate real-world safety and effectiveness of OAB treatments, residual bias due to unmeasured confounding and/or confounding by indication are important considerations. Falsification analysis, in which clinically irrelevant endpoints are tested as a reference, can be used to assess residual bias. The objective in this study was to compare baseline cardiovascular risk among OAB patients by treatment, and assess the presence of residual bias via falsification analysis of OAB patients treated with mirabegron or antimuscarinics, to determine whether clinically relevant comparisons across groups would be feasible. Linked electronic health record and claims data (Optum/Humedica) for OAB patients in the United States from 2011–2015 were available, with index defined as first date of OAB treatment during this period. Unadjusted characteristics were compared across groups at index and propensity-matching conducted. Falsification endpoints (hepatitis C, shingles, community-acquired pneumonia) were compared between groups using odds ratios (ORs) and 95% confidence intervals (CI). The study identified 10,311 antimuscarinic- and 408 mirabegron-treated patients. Mirabegron patients were predominantly older males, with more comorbidities. The analytic sample included 1,188 antimuscarinic patients propensity-matched to 396 mirabegron patients; after matching, no significant baseline differences remained. Estimates of falsification ORs were 0.7 (CI:0.3–1.7) for shingles, 1.5 (CI:0.3–8.2) for hepatitis C, 0.8 (CI:0.4–1.8) and 0.9 (CI:0.6–1.4) for pneumonia. While propensity matching successfully balanced observed covariates, wide CIs prevented definitive conclusions regarding residual bias. Accordingly, further observational comparisons by treatment group were not pursued. In real-world analysis, bias-detection methods could not confirm that differences in cardiovascular risk in patients receiving mirabegron versus antimuscarinics were fully adjusted for, precluding clinically relevant comparisons across treatment groups.

Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review

ABSTRACTIntroduction: Generalized anxiety disorder (GAD) often begins during adolescence or early adulthood and persists throughout the lifespan. Randomized controlled trials support the efficacy of selective serotonin and selective serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively), as well as benzodiazepines, azapirones, anti-adrenergic medications, melatonin analogs, second-generation antipsychotics, kava, and lavender oil in GAD. However, psychopharmacologic treatment selection requires clinicians to consider multiple factors, including age, co-morbidity, and prior treatment.Areas covered: The authors review the literature concerning pharmacotherapy for pediatric and adult patients with GAD with specific commentary on the efficacy and tolerability of selected agents in these age groups. The authors describe an algorithmic approach to the pediatric and adult patient with GAD and highlight considerations for the use of selected medications in these patients.Expert opinion: In adults with GAD, SSRIs and SNRIs represent the first-line psychopharmacologic treatment while second-line pharmacotherapies include buspirone, benzodiazepines, SGAs, and pregabalin. In pediatric patients with GAD, SSRIs should be considered the first line pharmacotherapy and psychotherapy enhances antidepressant response.

Systematic review with network meta-analysis: first- and second-line pharmacotherapy for moderate-severe ulcerative colitis.

There are limited data to inform positioning of agents for treating moderate-severe ulcerative colitis (UC). To assess comparative efficacy and safety of different therapies as first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor(TNF)-α) agents for moderate-severe UC, through a systematic review and network meta-analysis, and appraise quality of evidence (QoE) using grading of recommendations, assessment, development and evaluation (GRADE) approach. We identified randomised controlled trials (RCTs) in adults with moderate-severe UC treated with anti-TNF agents, anti-integrin agents and janus kinase (JAK) inhibitors, as first-line or second-line agents, and compared with placebo or another active agent. Efficacy outcomes were induction/maintenance of remission and mucosal healing; and safety outcomes were serious adverse events and infections. Network meta-analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities. In biologic-naïve patients (12 trials, no head-to-head comparisons), infliximab and vedolizumab were ranked highest for induction of clinical remission (infliximab: odds ratio [OR], 4.10 [95% confidence intervals [CI], 2.58-6.52]; SUCRA,0.85; vedolizumab:SUCRA,0.82) and mucosal healing (infliximab:SUCRA,0.91; vedolizumab:SUCRA,0.81) (moderate QoE). In patients with prior anti-TNF exposure (4 trials, no head-to-head comparisons), tofacitinib was ranked highest for induction of clinical remission (OR, 11.88 [2.32-60.89]; SUCRA, 0.96) and mucosal healing (moderate QoE). Differences in trial design limited comparability of trials of maintenance therapy for efficacy. Vedolizumab was ranked safest in terms of serious adverse events (SUCRA, 0.91), and infection (SUCRA, 0.75) in maintenance trials. Infliximab and vedolizumab are ranked highest as first-line agents, and tofacitinib is ranked highest as second-line agent, for induction of remission and mucosal healing in patients with moderate-severe UC, based on indirect comparisons. Head-to-head trials are warranted to inform clinical decision-making with greater confidence.

Burden Of Diabetes Mellitus In Patients With Acromegaly Treated With Second-Line Pharmacotherapy In Spain

Burden Of Diabetes Mellitus In Patients With Acromegaly Treated With Second-Line Pharmacotherapy In Spain

PnPP-19, A Spider Toxin Derivative: New Hope for the Treatment of Sexual Dysfunction?

The incidence of erectile dysfunction (ED) is increasing every year worldwide, and affects primarily those patients that suffer from vascular diseases, such as diabetes and hypertension. There is an increasing number of patients for whom first-line and second-line pharmacotherapy are not indicated. Animal venoms and toxins have been envisaged as pharmacological tools that enable elucidating the mechanisms that lead to erectile function, as well as give hints for drug development to treat ED. Recent studies have demonstrated the promising action of the synthetic peptide PnPP-19, derived from a spider toxin (PnTx2-6), on erectile function. This peptide potentiates erection at 4 and 8 Hz in vivo and ex vivo. It shows no apparent toxicity and presents low immunogenicity to mice. It does not affect sodium channels or rat hearts. Therefore, PnPP-19 may emerge as a new pharmacological tool and shows favorable properties as a bioactive molecule in the treatment of ED.

Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial

Metformin is the recommended first-line pharmacotherapy for patients with type 2 diabetes. There is no consensus on the optimum second-line pharmacotherapy. We compared the efficacy and safety of the sodium glucose cotransporter 2 inhibitor empagliflozin and the sulfonylurea glimepiride as add-on to metformin in patients with type 2 diabetes. In this double-blind phase 3 trial, patients (aged ≥18 years) with type 2 diabetes and HbA1c concentrations of 7-10%, despite metformin treatment and diet and exercise counselling, were randomly assigned in a 1:1 ratio with a computer-generated random sequence, stratified by HbA1c, estimated glomerular filtration rate (eGFR), and region, to empagliflozin (25 mg once daily, orally) or glimepiride (1-4 mg once daily, orally) as add-on to metformin for 104 weeks. Patients and investigators were masked to treatment assignment. The primary endpoint was change from baseline in HbA1c levels at weeks 52 and 104. Differences in the primary endpoint were first tested for non-inferiority (based on a margin of 0·3%). If non-inferiority was shown, differences in the primary endpoint at week 104 were then tested for superiority. Analysis was done on the full-analysis set-ie, patients who were treated with at least one dose of study drug and had a baseline HbA1c value. This study is registered with ClinicalTrials.gov, number NCT01167881. A 104-week extension is ongoing. Between August, 2010, and June, 2011, 1549 patients were randomly assigned to receive empagliflozin (n=769) or glimepiride (n=780); four patients in the empagliflozin group did not receive the assigned treatment. Empagliflozin was non-inferior to glimepiride at both timepoints. At week 104, adjusted mean difference in change from baseline in HbA1c with empagliflozin versus glimepiride was -0·11% (95% CI -0·19 to -0·02; p=0·0153 for superiority). Adverse events were reported in 661 (86%) patients treated with empagliflozin and 673 (86%) patients treated with glimepiride. Severe adverse events were reported in 72 (9%) patients in the empagliflozin group and 68 (9%) in the glimepiride group. Serious adverse events were reported in 119 (16%) patients in the empagliflozin group and 89 (11%) in the glimepiride group. Confirmed hypoglycaemic adverse events (plasma glucose ≤3·9 mmol/L or requiring assistance) at week 104 were reported in 19 (2%) patients treated with empagliflozin and 189 (24%) patients treated with glimepiride. Empagliflozin might be an effective and a well tolerated second-line treatment option for patients with type 2 diabetes who have not achieved good glycaemic control on metformin. Boehringer Ingelheim and Eli Lilly.

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice.

Strategies for assisting smoking cessation include behavioural counselling to enhance motivation and to support attempts to quit and pharmacological intervention to reduce nicotine reinforcement and withdrawal from nicotine. Three drugs are currently used as first line pharmacotherapy for smoking cessation, nicotine replacement therapy, bupropion and varenicline. Compared with placebo, the drug effect varies from 2.27 (95% CI 2.02, 2.55) for varenicline, 1.69 (95% CI 1.53, 1.85) for bupropion and 1.60 (95% CI 1.53, 1.68) for any form of nicotine replacement therapy. Despite some controversy regarding the safety of bupropion and varenicline, regulatory agencies consider these drugs as having a favourable benefit/risk profile. However, given the high rate of psychiatric comorbidity in dependent smokers, practitioners should closely monitor patients for neuropsychiatric symptoms. Second-line pharmacotherapies include nortriptyline and clonidine. This review also offers an overview of pipeline developments and issues related to smoking cessation in special populations such as persons with psychiatric comorbidity and pregnant and adolescent smokers.