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Esketamine approved in the US as the first ever monotherapy for treatment-resistant depression in adults
For the first time, the Food and Drug Administration (FDA) has approved a ketamine-related drug as a standalone treatment for adults with major depressive disorder (MDD). Esketamine nasal spray is approved for patients who have treatment-resistant depression (TRD) - defined as an inadequate response to at least two oral antidepressants.
The approval follows a multicentre randomised controlled trial which demonstrated the rapid efficacy of esketamine monotherapy. Within the first 24 hours of the initial dose, participants experienced significant improvements in their Montgomery-Asberg Depression Rating Scale (MADRS) total score, with the effects persisting for at least 4 weeks. By the fourth week, 22.5% of patients receiving esketamine had achieved remission (MADRS total score ≤12), compared to 7.6% in the placebo group.
Until now, esketamine had been approved in the US exclusively as an adjunctive therapy alongside an oral antidepressant for two indications in adults: as a treatment for TRD, and for those with MDD experiencing suicidal ideation or behaviour.
This expanded indication makes esketamine accessible to individuals with TRD who are not on an antidepressant or who wish to discontinue their current one, which may help to overcome treatment barriers owing to negative experiences with oral antidepressants, such as poor tolerability.
Despite growing clinical adoption of esketamine, several questions remain. The optimal patient profile for treatment response, how long therapeutical effects might persist, and the appropriate duration of therapy all require further investigation. While no longer considered a last-resort treatment, esketamine is not a first- or second-line treatment.
Esketamine is approved only for use in an appropriate certified clinical setting under the supervision of a health care provider; typically this will mean referring to a designated treatment facility offering esketamine. A key practical consideration is the logistical and occupational commitments required of patients; for example, the need to take time away from work and to arrange necessary transport and support. The drug must be self-administered by the patient, who is supervised by a health care provider in a certified medical office, and the patient monitored for at least 2 hours because of the risk of sedation, respiratory depression, difficulty with attention, judgement and thinking (dissociation), suicidal thoughts and behaviours, and the potential for drug misuse. For these reasons, esketamine is only available via a restricted distribution programme in the US.
People with poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. Esketamine is contraindicated in patients with aneurysmal vascular disease, arteriovenous malformation, or intracerebral haemorrhage.
Esketamine is available in Europe; however, it is not currently approved for monotherapy. Availability of esketamine varies according to the country of practice and relevant regulatory approval.
NICE recommends cytisinicline for smoking cessation, expanding treatment options for clinicians in the UK
The National Institute for Health and Care Excellence (NICE) has updated its guidelines on smoking cessation, now recommending cytisinicline (also known as cytisine) as a pharmacological treatment option for adults aged 18-65 years who want to quit smoking. This addition places cytisinicline alongside other well-established interventions such as varenicline, nicotine replacement therapy (NRT), and bupropion.
A plant-derived alkaloid, cytisinicline acts as a partial agonist at the alpha-4 beta-2 nicotinic acetylcholine receptor, and has been used for decades in Eastern Europe. A growing body of evidence suggests that cytisinicline outperforms placebo and NRT and offers comparable effectiveness to varenicline in aiding smoking cessation. However, the NICE update committee acknowledged that evidence remains limited for certain population subgroups, especially those affected by health inequalities.
While the drug may increase the risk of nausea and insomnia compared to placebo or NRT, these adverse effects were generally mild. In contrast, varenicline was associated with a higher incidence of nausea. The committee noted that symptoms such as nausea and headaches may also be related to nicotine withdrawal, complicating the interpretation of adverse effect profiles.
NICE advises setting a quit date within the first 5 days of treatment. It stresses that cytisinicline, as with all types of pharmacotherapy for smoking cessation, should be prescribed within a comprehensive approach that includes behavioural support. It is not recommended for use in pregnant or breastfeeding women, nor for individuals under 18 or over 65 years.
This update offers primary care practitioners an additional, evidence-based tool to aid in smoking cessation, and provides a new option for patients seeking effective smoking cessation strategies. Healthcare professionals are encouraged to discuss the available options with patients to determine the most suitable treatment based on individual needs and preferences.
Guidelines recommend statins for people living with HIV to prevent cardiovascular events
People living with HIV are at greater risk of atherosclerotic cardiovascular disease (ASCVD). In order to prevent major cardiovascular events such as stroke and heart attacks, guidelines now recommend statin therapy for primary prophylaxis in people over 40 years of age who are living with HIV.
The new recommendations were informed by findings from the National Institutes of Health (NIH)-supported REPRIEVE (Randomised Trial to Prevent Vascular Events in HIV) trial, a large randomised controlled trial undertaken in people living with HIV. The trial found that pitavastatin (a moderate-intensity statin) may offset the high risk of cardiovascular disease in people living with HIV by 35%, compared to placebo, after a median follow-up of 5 years.
As a consequence of this trial, the US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents with HIV now recommends at least moderate-intensity statin therapy for primary prophylaxis in people 40-75 years of age with HIV who have low to intermediate (<20%) 10-year ASCVD risk estimates. People with HIV who are less than 40 years of age or have a 10-year ASCVD risk estimate ≥20% should be treated as per the general population, based on evidence-based guidelines.
The British HIV Association (BHIVA) also recommends offering statin therapy to people living with HIV over the age of 40 years, regardless of their estimated ASCVD risk or lipid profile. Patients with an estimated 10-year ASCVD risk ≥5% should be prioritised for primary prophylaxis. [NEW REF: https://www.bhiva.org/BHIVA-rapid-guidance-on-the-use-of-statins-for-primary-prevention-of-cardiovascular-disease]
People living with HIV are twice as likely to develop cardiovascular disease, which may be related to the disease itself and/or the use of antiretroviral therapy (ART). The global burden has tripled over the past two decades and is responsible for 2.6 million disability-adjusted life years.
FDA approves olezarsen for the treatment of familial chylomicronemia syndrome
Olezarsen, a ligand conjugated antisense oligonucleotide targeting apo C-III, has been shown to reduce triglyceride (TG) levels by >50% and acute pancreatitis risk by >85% in patients with familial chylomicronemia syndrome (FCS). Olezarsen has been approved by the US Food and Drug Administration as an adjunct to diet to reduce TG levels in adults with FCS. Note this indication is for a rare and severely affected subgroup of patients with hypertriglyceridaemia only. Olezarsen is not approved in Europe as yet.
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Introducing our new Frailty topic
Unlock essential insights into frailty with the latest addition to BMJ Best Practice.
Recognising frailty is crucial. It’s an independent risk factor for adverse health outcomes, such as increased hospitalisations. By identifying frailty, we can tailor interventions to mitigate risks and improve outcomes. This topic is designed to equip you with the tools you need to navigate the complexities of frailty management, by helping you to:
- Identify frailty
- Navigate an ageing population
- Understand the implications of frailty
- Support the MDT
Have you used our Comorbidities Manager?
Managing the treatment of patients with comorbidities is hard – clinical guidelines only focus on single conditions – but failure to manage comorbidities leads to worse clinical outcomes and longer lengths of stay.
Our unique Comorbidities Manager* provides guidance on the treatment of a patient’s acute condition alongside their preexisting comorbidities.
*This feature is only available if your institution has purchased the Comorbidities Manager. If you have access it will appear under the ‘Your Profile’ section in the menu at the top of the page.
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One in three adults suffer from multiple chronic conditions and most patients in the acute setting have more than one medical condition.
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