When selecting an antidepressant, a number of factors must be considered. These considerations are summarized under the mnemonic STEPS: Safety, Tolerability, Efficacy, Payment (eg, cost-effectiveness), and Simplicity of use. Venlafaxine is the first of a new class of antidepressants that selectively blocks the serotonin and noradrenaline uptake pumps without blocking muscarinic, histaminergic and adrenergic receptors or inhibiting sodium fast channels. Because venlafaxine avoids these mechanisms of action, it has a wide therapeutic index, an improved tolerability profile and a reduced risk of causing pharmacodynamically mediated drug-drug interactions when compared to tricyclic antidepressants (TCAs). In contrast to some other new antidepressants, venlafaxine also avoids effects on cytochrome P450 which are likely to cause clinically meaningful, pharmacokinetically mediated drug-drug interactions. The effects on the uptake pumps of both serotonin and noradrenaline appear to be responsible for some of venlafaxine's unique features in terms of antidepressant efficacy, including its ascending antidepressant dose-response curve and its apparent rapid onset of antidepressant action at the upper end of its clinically relevant dosing range. Venlafaxine is effective in a broad spectrum of patients, including outpatients and inpatients, those with and without melancholia, patients with symptoms of anxiety or agitation or retardation and patients with first time or recurrent episodes of major depression. An important factor when selecting an antidepressant is the simplicity of the dosing regimen and the ability to rapidly and confidently achieve the optimal dose for the patient. In this regard, venlafaxine can be initiated at a clinically effective dose from the beginning. If the patient fails to respond to this dose, there is evidence that increased antidepressant efficacy can be achieved by increasing the dose rather than having to resort to an augmentation strategy or switch to another class of antidepressants. In the immediate release form, venlafaxine has proven antidepressant efficacy when using a twice-or three-times-a-day schedule. A sustained release formulation is expected to be marketed soon and will permit once-a-day-dosing.

The benefits of an antidepressant with an early or rapid onset of action include a more rapid resolution of the debilitating symptoms of depression, a potential reduction in the risk of suicide and cost savings associated with a reduction in hospitalization. While these benefits are valuable, this promise has yet to be fulfilled by any antidepressant. Venlafaxine is a unique serotonin-noradrenaline reuptake inhibitor (SNRI) which produces rapid and prolonged desensitization of β-adrenergic receptors in preclinical studies after both acute and chronic administration of venlafaxine. Results from placebo-controlled and active comparator clinical studies provide evidence that venlafaxine may have an early onset of activity which is most apparent at higher dosages. The early onset is most apparent with rapid escalation of the venlafaxine dosage, and the incidence, therefore, of side effects tends to be higher early after initiating therapy with venlafaxine. Thus, venlafaxine may fill the long awaited need for an antidepressant with an early onset of action.

The ventricular assist device is being increasingly used as a “bridge-to-transplant” option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharmacotherapy. Pharmacokinetic/pharmacodynamic alterations affecting pharmacotherapy are increasingly discovered in children supported with extracorporeal membrane oxygenation, another form of mechanical circulatory support. Similarities between extracorporeal membrane oxygenation and ventricular assist devices support the hypothesis that similar alterations may exist in ventricular assist device-supported patients. We conducted a literature review to assess the current data available on pharmacokinetics/pharmacodynamics in children with ventricular assist devices. We found two adult and no paediatric pharmacokinetic/pharmacodynamic studies in ventricular assist device-supported patients. While mechanisms may be partially extrapolated from children supported with extracorporeal membrane oxygenation, dedicated investigation of the paediatric ventricular assist device population is crucial given the inherent differences between the two forms of mechanical circulatory support, and pathophysiology that is unique to these patients. Commonly used drugs such as anticoagulants and antibiotics have narrow therapeutic windows with devastating consequences if under-dosed or over-dosed. Clinical studies are urgently needed to improve outcomes and maximise the potential of ventricular assist devices in this vulnerable population.

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.

Background: Anticholinergic and sedating medications are generally contraindicated in those with cognitive decline. We examined trends in medication use by patients at initial presentation to a rural and remote memory clinic (RRMC) between March 2004 and June 2015 to determine whether patterns of medication use have changed. Methods: The first 444 patients seen at the RRMC between 2004 and 2015 were included in this analysis. Medication lists were collected at the patient’s initial visit, and it was noted whether patients were taking anticholinergic or potentially sedating drugs. Statistical analysis (Spearman’s correlation) was conducted to examine trends in medication use over time. Results: Patients were on a mean of 5.18 medications (standard deviation, 3.46). Ninety-one patients (20.5%) were taking at least one anticholinergic medication. There was a decline (25.0% in 2004 to 12.5% in 2014) in percentage of patients presenting with anticholinergic medications over the 11 years of this study (Spearman’s correlation coefficient =−0.64, p=0.035). The prevalence of drugs acting on the central nervous system trended toward an increase, but this was not statistically significant. Sixty-three patients (14.2%) presented to the RRMC already taking a cholinesterase inhibitor. Conclusions: The most encouraging statistic to come from this study is a decline in anticholinergic medication use in this rural population. Prescribers must be properly informed to ensure that the number of medications per patient does not continue to rise, that medications are used only as necessary, and that potentially deleterious medications are avoided.

Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related chronic infections represent a major health problem worldwide. Although the efficacy of HBV and HCV treatment has improved, several important problems remain. Current recommended antiviral treatments are associated with considerable expense, adverse effects and poor efficacy in some patients. Thus, several alternative approaches have been attempted. To review the clinical experiences investigating the use of lipid- and water-soluble vitamins in the treatment of HBV- and HCV-related chronic infections, PubMed, the Cochrane Library, MEDLINE and EMBASE were searched for clinical studies on the use of vitamins in the treatment of HBV- and HCV-related hepatitis, alone or in combination with other antiviral options. Different randomised clinical trials and small case series have evaluated the potential virological and/or biochemical effects of several vitamins. The heterogeneous study designs and populations, the small number of patients enrolled, the weakness of endpoints and the different treatment schedules and follow-up periods make the results largely inconclusive. Only well-designed randomised controlled trials with well-selected endpoints will ascertain whether vitamins have any role in chronic viral hepatitis. Until such time, the use of vitamins cannot be recommended as a therapy for patients with chronic hepatitis B or C.