Children on cystic fibrosis drugs may experience severe mood changes

A cystic fibrosis drug dubbed ‘the holy grail’ by doctors may trigger mood changes, behavioural problems, insomnia and talk of suicide in children as young as three, disturbing research has revealed.

The medicine, Kaftrio, which was approved for a full NHS roll-out last month, eases the worst symptoms of the genetic disease and is expected to dramatically improve life expectancy.

But a new study, published last week in The Lancet, gives clear indication the drug can affect mental health. Researchers gave doses of the medication to 197 children aged two to five. After one month, 93 of them – 47 per cent – were reported to have sudden, abnormal changes in behaviour.

A third developed attention-deficit hyperactivity disorder (ADHD), which leads to poor concentration, irritability and impulsive behaviour. Others became aggressive. One in ten developed ‘abnormal sadness’ and one had suicidal thoughts. These changes persisted in 58 of the 93 children and stopping treatment led to an ‘immediate recovery in symptoms’.

It is unclear why the drug might cause mental health problems, or who might be worst affected.

French scientists behind The Lancet study speculate that it may tip the balance of substances in the brain involved in feelings of anxiety and depression. They believe that until there is better understanding of what the drug is doing inside the body, caution should be taken when prescribing it to children.

Cystic fibrosis (CF) is a life-long genetic condition that causes the body to produce thick mucus that clogs the digestive system and causes lung infections. In the 1970s, few patients lived beyond their teens – now about half make it into their 40s.

Patients, who are often hospitalised by the effects of the disease, have called Kaftrio ‘close to a cure’ as it helps them to live normal lives. But since it was made available in 2020, stories have emerged of psychiatric issues.

Two years ago The Mail on Sunday was the first to sound the alarm, after adults with CF came forward with a raft of problems they said were triggered by the tablets, including severe depression, debilitating brain fog and memory problems.

One woman in her early 30s began to experience extreme anger and depression, migraines, seizures and temporary paralysis. In two shocking instances reported by this newspaper in 2022, a woman attempted to take her own life and a boy of nine with no history of mental health issues began self harming after starting on similar medication.

At the time, healthcare professionals and the CF Trust suggested these issues could be a result of the life-changing nature of treatment – not the drug itself. But following our reports, patient advice leaflets in Kaftrio packets were updated to include depression as a potential side effect.

Kaftrio, as well as similar drugs Symkevi, Orkambi and Kalydeco, are known as CFTR modulators, as they correct the fault in a gene called CFTR that causes CF’s most debilitating symptoms. They are all made by US-based pharmaceutical firm Vertex.

A spokesman for the company last night said: ‘We conducted an in-depth analysis of all available data, and based on this comprehensive assessment we find no causal relationship between Kaftrio and psychiatric events, nor do we find a causal association of Kaftrio with low mood, problems with sleep, concentration, and memory, or challenging behaviour in children and young people.’

We contacted the mother of the nine-year-old who previously spoke to the MoS about the side effects her son suffered while taking Symkevi and Kalydeco.

She said the drugs had caused her ‘happy’ boy to become constantly tearful. Later she discovered he had begun scratching his face and arms with a razor.

His consultant agreed that he should stop the drugs, and he quickly returned to normal.

Now 11, last summer the boy was started on Kaftrio. His mother says: ‘The problems started almost as soon as he took the medication – it was like a switch. He went from a happy, bubbly and confident boy who loves football to tearful and angry. And the self harming came back, which is terrifying.’

Again he was taken off the drug, and swiftly returned to normal.

‘I’m on a Facebook group for parents of children with CF. There are endless posts about behavioural problems. I can’t help [but think] it’s being caused by Kaftrio.’

David Ramsden of the CF Trust said that while the effects of Kaftrio have been positive for most, ‘we know this has not been the case for everyone’.