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FDA approves novel antipsychotic lumateperone as a new adjunctive treatment for depression
The US Food and Drug Administration (FDA) has approved lumateperone, a drug originally developed to treat psychosis, as an adjunctive treatment for major depressive disorder.
Lumateperone is an atypical antipsychotic with a distinctive mechanism of action. It is a serotonin 5-HT2A receptor antagonist and a partial agonist at central dopamine D2 receptors. Already approved for schizophrenia and depressive episodes associated with bipolar disorder, lumateperone gained approval in November 2025 as an adjunctive therapy to antidepressants for major depressive disorder in adults who experience only partial response to standard antidepressants.
The decision was underpinned by two positive phase 3 randomised controlled trials, demonstrating that lumateperone, when added to an oral antidepressant, significantly reduced depressive symptoms compared with placebo. Participants tolerated the treatment well over six weeks, with somnolence, dry mouth, diarrhoea, and dizziness the most frequently reported adverse effects. Importantly, rates of metabolic disturbance, extrapyramidal symptoms, and prolactin elevation, often problematic with other antipsychotic augmentation strategies, remained low. An accompanying open-label extension study suggests this favourable tolerability profile may persist over 6 months.
Lumateperone’s unique mechanism of action and safety profile may make it a valuable option in the future for select patients with depression, particularly those with a partial response to antidepressants, or for whom there are concerns about tolerability with other augmentation treatments. However, longer-term and real-world data are lacking, and head-to-head trials with established augmentation drugs are still needed. Additionally, availability in the US is limited by cost. Lumateperone is not currently approved in Europe.
AMT-130 gene therapy slows disease progression in patients with Huntington’s disease
AMT-130, a gene therapy which uses RNA interference to lower levels of mHTT (mutant huntingtin) protein, has shown promising results in one phase 1/2 study. Based on information from press releases, initial topline results from the European arm of the study indicate that the therapy has the potential to slow disease progression, giving hope to patients with Huntington’s disease. The study met its primary endpoint, with a statistically significant 75% slowing of disease progression with high-dose AMT-130 compared with control at 36 months, as measured using the composite Unified Huntington’s Disease Rating Scale. A secondary endpoint was also met, with high-dose AMT-130 showing a statistically significant 60% slowing of disease progression as measured by Total Functional Capacity. Favourable trends were also found across additional clinical measures of motor and cognitive function, mean cerebrospinal fluid neurofilament light protein (NfL) levels reduced below baseline at 36 months, and the therapy was well tolerated with a manageable safety profile.
A single dose of the drug is expected to last a lifetime. The US Food and Drug Administration (FDA) has previously granted AMT-130 breakthrough therapy designation and regenerative medicine advanced therapy designation, programmes designed to accelerate the development and review of new drugs. It is anticipated that a biologics license application will be submitted to the FDA in 2026 requesting accelerated approval of the drug. AMT-130 currently also has orphan drug designation in Europe.
FDA approves nerandomilast for treatment of idiopathic pulmonary fibrosis in adults
Idiopathic pulmonary fibrosis (IPF) has few treatment options and currently relies on antifibrotic agents (nintedanib and pirfenidone) and supportive therapy. Nerandomilast, an oral phosphodiesterase-4 (PDE-4) inhibitor, is the first new treatment for IPF approved by the US Food and Drug Administration (FDA) in more than 10 years.
One randomised, double-blind, placebo-controlled phase 3 trial demonstrated that people with IPF taking nerandomilast had a significantly smaller decline in forced vital capacity (FVC) compared with placebo-treated groups over a period of 1 year. Nerandomilast can be used alone or in combination with antifibrotic therapy.
This treatment has the potential to impact the care of many patients, including those with:
- intolerance to an antifibrotic agent and
- continued worsening in lung function despite use of an antifibrotic agent.
WHO declares mpox emergency over
The World Health Organization (WHO) declared that the mpox public health emergency of international concern (PHEIC) was over on 5 September 2025. The PHEIC was first declared in August 2024 due to various mpox outbreaks in Africa.
The decision to end the PHEIC is based on a sustained decline in the number of cases and deaths in the Democratic Republic of the Congo (DRC), and other affected countries including Uganda, Sierra Leone, and Burundi, as well as the fact that there is now a better understanding of the drivers of transmission and the risk factors for disease severity. Despite lifting the PHEIC, the WHO’s mpox response will continue.
In the past 12 months, approximately 43,800 laboratory-confirmed cases of mpox have been reported in Africa, including 186 deaths (as of 28 September 2025). The three countries with the majority of cases were the DRC, Uganda, and Sierra Leone. The spread in Africa was due to two distinct outbreaks:
- A clade Ia outbreak primarily in mpox-endemic areas and mainly affecting children.
- A clade Ib outbreak in the eastern part of the country that spread rapidly and reached neighboring countries that had not previously reported cases.
The WHO has assessed the overall global public health risk to be moderate for clade Ib and clade IIa mpox, and low for clade Ia and IIb mpox.
This was the second time that the WHO declared an mpox outbreak to constitute a PHEIC, with the first one declared in July 2022 due to a global outbreak of clade IIb mpox in countries that had not previously experienced cases. The emergency was declared over in May 2023 as the number of cases had decreased significantly since their peak in August 2022. However, clade II mpox is still circulating globally with outbreaks in many countries.
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Prostate cancer: explore our topic
Prostate cancer is the second most common cancer and the fifth leading cause of cancer mortality in men worldwide. This topic will help you to learn how to:
- Diagnose the condition confidently
- Manage patients effectively
- Share information with patients
- Advise patients about PSA testing
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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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At a glance
One in three adults suffer from multiple chronic conditions and most patients in the acute setting have more than one medical condition.
- Treat patients with comorbidities with confidence
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