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ACKR1 genetic testing should be offered before starting clozapine treatment

A simple genetic test should be offered before starting a vital medication for treatment-resistant schizophrenia, according to a new Perspective led by UCL researchers.

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  • ACKR1 genetic testing should be offered before starting clozapine treatment

Some people are unnecessarily excluded from a vital medication for treatment-resistant schizophrenia, according to a new Perspective published this week in Nature Mental Health. 

Clozapine is the most effective and only licensed medication for treatment-resistant schizophrenia. However, in about 1 in 200 people taking clozapine, the number of white blood cells will drop, increasing their risk of infection. To manage this risk, people taking clozapine are required to have regular blood tests. If their number of white blood cells drops below a certain threshold, clozapine has to be stopped indefinitely. 

Some people, however, have naturally low numbers of white blood cells but are not at risk of infection. These people have ADAN, which is caused by a difference in a gene called ACKR1 and is common in people with African ancestry. The minimum white blood cell count threshold is lowered for people with ADAN to allow them to continue clozapine without stopping unnecessarily.

However, in this week’s Perspective, the authors found – after systematically reviewing the literature – that ADAN goes frequently undetected. This means that people with ADAN are unfairly excluded from vital clozapine treatment despite it being safe for them to receive it. 

To address this, the authors – comprising an expert team of psychiatrists, haematologists, and clinical scientists – provide a framework for offering a new genetic test to rapidly identify people with ADAN right at the beginning of their clozapine treatment. This approach, the authors state, will allow more people to benefit from clozapine, giving them the best chance of recovery while saving NHS resources.  

Dr Steve Murtough, the Perspective’s first author, says: 

“We want people who need and can safely receive clozapine to be able to do so – but we’ve found that many people with ADAN are being unfairly excluded, simply because mental health services are not currently equipped to identify ADAN quickly and at scale. In this Perspective, we provide a framework for how mental health services can incorporate a simple genetic test into existing practice, so that ADAN can be rapidly identified at the beginning of clozapine treatment.”

Links

  • Perspective in Nature Mental Health
  • Dr Stephen Murtough’s academic profile
  • UCL Division of Psychiatry

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