Why are doctors doling out so many of the antibiotics now officially linked to suicidal thoughts?

Running towards a railway line, Ian Moore found himself sobbing hysterically and with his brain feeling ‘like it was on fire’. ‘I just wanted to end it all, I had no idea why, these terrible feelings had come out of nowhere,’ says Ian, 43, a former construction site foreman from Bristol.

Although he had been off work with a suspected prostate infection, he was ‘at the peak of my physical fitness — I love cycling, sometimes doing it every day’.

He was happy in his job and enjoying his life with partner Julie. As he explains: ‘I had no reason to be suddenly feeling suicidal. It was terrifying.’

‘I remember feeling a burning sensation in my brain and bladder, like I was being fried inside,’ he recalls.

The suicidal feelings appeared after just three days of starting a seven-day course of ciprofloxacin, one of a class of strong broad-spectrum antibiotics called fluoroquinolones, which are commonly prescribed to treat pneumonia, bronchitis and urinary tract infections. Fluoroquinolones include levofloxacin, moxifloxacin, norfloxacin and ofloxacin, as well as ciprofloxacin.

As Good Health has long highlighted, fluoroquinolones have been linked in some patients to serious long-term harm including tendon rupture; nerve, joint and muscle pain; fatigue; insomnia and gut problems.

Drug manufacturers say serious side-effects are rare, affecting 1 to 3 per cent of those who take them.

But Neal Millar, a professor of orthopaedic surgery and musculoskeletal science at Glasgow University, who treats patients for fluoroquinolone-related toxicity problems, says the true figure is closer to 10 to 15 per cent. To put this in context, last year there were more than 500,000 fluoroquinolone items prescribed in the community in England alone (this figure doesn’t include hospital prescriptions).

It is thought that these side-effects may be triggered by the drugs’ action on the mitochondria, the ‘batteries’ in all our cells.

Mounting evidence for these potential side-effects led to the Medicines & Healthcare products Regulatory Agency (MHRA) in 2019 highlighting the potential risks, although this had only a small impact on prescribing patterns.

Then, in August this year, it published a drug safety update reminder to prescribers, highlighting the risks of ‘disabling and potentially long-lasting or irreversible side effects . . .’ from fluoroquinolones, and said treatment should be discontinued at the first signs of a serious reaction, including tendon pain or inflammation.

And in another update, just a month later, it focused specifically on the risk of suicidal side-effects.

Although these are rare, the MHRA said: ‘Healthcare professionals prescribing fluoroquinolone antibiotics are reminded to be alert to the risk of psychiatric reactions, including depression and psychotic reactions, which may potentially lead to thoughts of suicide or suicide attempts. [They] are also reminded to advise patients to be alert to these risks.’

This latest update followed the inquest into the death in Huddersfield of recently retired cardiologist Dr Robert Stevenson in May 2022 at the age of 63. Eleven days after he had been prescribed ciprofloxacin for suspected prostatitis (inflammation of the prostate because of infection), he was found dead in woodland close to his home.

The coroner noted that Dr Stevenson had no previous history of depression and mental health problems; the inquest also heard that the prescribing doctor had not mentioned the possible suicide side-effect, as it was not in prescribing advice available at the time. Such was his concern, the coroner issued a Prevention of Future Deaths Report to the MHRA — essentially asking it to consider reviewing the current evidence to prevent future deaths.

Under the MHRA’s Yellow Card system for reporting drug side-effects, in the four years between 2019 and now, there were 2,226 reports for fluoroquinolone suspected adverse drug reactions.

For context, there were 3,171 for the antidepressant sertraline, with 22.1 million prescription items a year — more than 40 times the number of fluoroquinolone items prescribed each year — so proportionally there were significantly more for these antibiotics.

In its August drug safety update, the MHRA also addressed another concern, that fluoroquinolones are being over-prescribed — stressing that they should not be prescribed ‘for non-severe or self-limiting infections, or for mild to moderate infections unless other antibiotics are considered inappropriate’.

Fluoroquinolones are meant to be reserved for serious infections or those that have proved resistant to other medications but, increasingly, they have been prescribed as first-line treatments.

While research published in March 2023 in the journal Drug Safety showed that between 2016 and 2021 the number of prescriptions in the UK dropped, it also showed that the drugs are still being wrongly prescribed.

As Professor Millar, who takes referrals on fluoroquinolone damage from across the UK, argues, it’s a treatment often given when it’s not needed. ‘In many cases a different type of antibiotic could have been used,’ he says.

He adds that while it’s welcome that the MHRA has listened to patients about the side-effects, in his view the drugs ‘should only be prescribed in hospital settings for serious infections — ‘or at the very least a warning should flash up on a GP computer screen’.

Ian was prescribed ciprofloxacin for suspected prostatitis, which had been causing him pelvic pain. ‘The doctor didn’t say anything about side-effects,’ he says.

‘I took two tablets a day for three days, then suddenly I was thinking about taking my own life.’

Ian remembers little about his frightening ordeal, just that he was upset and crying.

A stranger, noticing his distress, asked if he was all right — this probably saved Ian’s life.

‘It was like I woke up in that moment and realised what I was about to do,’ says Ian. ‘I was shocked and wondered how I’d got there — and why I’d suddenly had those thoughts.’

Ian arrived home in an agitated state and told Julie what had happened. Although worried because it was so out of character, she put it down to the infection. Ian carried on taking the tablets for three more days then stopped because his condition had deteriorated rapidly — he had repeated suicidal thoughts and became increasingly manic and unable to sleep.

Believing that he still had an infection, he went to A&E and described the acid-like burning sensation in his pelvic floor and his suicidal thoughts. ‘The doctor told me I was anxious and prescribed me more ciprofloxacin,’ says Ian. ‘But I threw them away as, by then, I was convinced they were harming me.

‘Two days later, I was having lunch with Julie in a restaurant and burst out crying. I felt unbalanced — as if I was going to fall over — and developed tinnitus and blurred vision.

‘Julie took me straight to A&E, where still convinced it was infection-related, they prescribed me another antibiotic [Bactrim, which is not a fluoroquinolone].’

Having lost 5 kg in weight in just a few weeks, Ian went back to his GP and asked her if his symptoms could be an adverse reaction to the antibiotic. But the GP referred Ian for a CT scan, worried that he had cancer. When the scan came back clear a few weeks later, he was referred to a neurologist.

‘While I waited, I researched my symptoms online and found out about fluoroquinolone toxicity syndrome. I also read about Professor Millar and contacted him — he diagnosed me with it in July, two months after my symptoms began.’

Ian’s experience is far from unique, according to Fluoroquinolone Toxicity Support UK, a patient group that campaigns for greater recognition and improved treatments of the syndrome.

‘Patients are being gaslighted and told it’s all in their head by their doctors. Not enough of them know about fluoroquinolone toxicity,’ says Miriam Knight, co-founder of the support group.

After years of campaigning, she says the MHRA’s recognition of psychiatric symptoms is a significant step forward ‘when you consider how much in denial they have been about this previously.

‘But we want greater awareness among doctors and the public of the damage these drugs can do and to stop them being overprescribed’.

Psychiatrist Professor David Healy, director of RxISK, a drug safety campaign group, who has been an expert witness in suicide trials involving prescription medications, agrees that the side-effects of fluoroquinolones aren’t often recognised by doctors.

‘Doctors just don’t make the connections between fluoroquinolone antibiotics and suicidal symptoms, despite it being reported in medical literature for years,’ he told Good Health.

‘Medicine is too hyper-specialist these days: the kidney doctor might prescribe a kidney drug that causes eye side-effects, but the eye specialists don’t know anything about kidney drugs and so just see the eye problem.’

Professor Healy says he has doctor friends who have described going into a dissociative state, where they felt disconnected from the world, after taking fluroquinolones. He was also contacted by the family of a young man who had been prescribed a high dose of ciprofloxacin before and after surgery to straighten his nose and noticed that he seemed out of sorts.

‘He started having visual hallucinations and hearing things that weren’t there — he withdrew socially and stayed in his room at university and became isolated and depressed,’ says Professor Healy.

‘When he went to his doctor and said he’d only been feeling like that since he’d taken ciprofloxacin, his doctor didn’t listen and instead prescribed him an anti-psychotic drug. That made things worse, and he took his own life.

‘I have seen other people diagnosed with mental illness where the diagnosis of fluoroquinolone toxicity was missed.

‘This happens a lot with drug side-effects generally, where they are mistaken for depression and the patient is prescribed an anti-psychotic drug, which can exacerbate the suicidal symptoms.

‘Drug companies say these reactions are rare, but they are rarely looked for in clinical trials and rarely reported — that’s not the same thing.’

A 2018 paper in the journal JAMA estimated that up to 200 different drugs can cause suicidal thoughts — but that number may be closer to 500 based on more recent research by RxISK, using clinical trial evidence, case reports and drug label listings, says Professor Healy.

‘Three weeks ago I attended the inquest of a 15-year-old boy who took the antibiotic doxycycline for his acne.’ The coroner’s verdict on cause of death is expected early next month.

‘And there was another case in 2019 involving a Cambridge University student, Alana Cutland, who fell to her death from a plane in Madagascar, after having a psychotic reaction to doxycycline she’d been prescribed as an antimalarial.’

The coroner who held the inquest into her death sent a Prevention of Future Deaths report to the MHRA, saying: ‘In my view the information sent out with the drug should be reviewed.’

Doxycycline is not a fluoroquinolone but a widely used type of tetracycline antibiotic; the drug leaflet does not mention psychotic reactions as a potential side-effect.

Professor Healy says all drugs can affect other areas of the body than the area they target.

‘A classic example is antidepressants that target serotonin in the brain — only 5 per cent of serotonin is in the brain, most of the serotonin is in the skin, blood and gut — so you can get effects all over the body.

‘People need to be made much more aware that all sorts of drugs can trigger suicidal feelings.’

Former foster carer Lisa Mitchell, who describes herself as previously ‘young for my age and happy-go-lucky’ also experienced terrible neurological side-effects and suicidal thoughts after she was prescribed a five-day course of ciprofloxacin for an ear and sinus infection in March last year.

‘I’d had one course of antibiotics, but stopped taking them after a few days as I felt they weren’t working and went back to my GP who prescribed ciprofloxacin,’ says Lisa, 44, a mother of two from Gateshead, Tyne and Wear.

‘She explained that they might cause aches and pains, but this was rare and nothing to worry about. When my neck started to hurt after three days, I thought it must be what the doctor was talking about, but then I developed numbness in both my arms.

‘By the following day I was delirious and hallucinating, seeing insects crawling in butter and flour,’ she says. ‘My nerves felt like they were burning and I started having electric jolts in my brain. It was really frightening.

‘I wasn’t sleeping and was wracked with pain. I felt like I was suddenly 90 years old — I had memory problems and bad brain fog.

‘I began to feel suicidal, I was calling a mental health crisis line every night and I felt I couldn’t take any more.

‘I think that it was only because I became so seriously ill that I didn’t go ahead. I also didn’t want to leave my kids alone.’

Lisa had been prescribed mild-dose antidepressants for a bereavement previously, but wasn’t taking them at the time she took ciprofloxacin because she no longer needed them.

She had also never had serious depression or suicidal thoughts before and blames ciprofloxacin for her symptoms.

Since stopping the medication, she has been plagued with neurological and physical symptoms (which include gut problems and losing 12 kg) yet she feels clinicians dismissed her, including a neurologist ‘who just wouldn’t acknowledge that ciprofloxacin had caused my problems,’ she says.

She was finally diagnosed after she contacted Professor Millar. ‘He was the first person who listened.’

He says that patients with long-term harm from fluoroquinolones need to have their symptoms acknowledged and be given a clear pathway to get the right treatment — this involves treating the symptoms individually, with specialised physiotherapy for tendon problems, for instance.

Eighteen months after he stopped taking ciprofloxacin, Ian is still experiencing symptoms such as tendonitis (inflamation of the tendons in his legs), muscle wasting in his legs and painful joints. He struggles to walk and, as well as losing over a stone of muscle mass, his weight has dropped from 11 st 5 lb (72 kg) to 9 st (57 kg) — he’s 5 ft 11 in — since taking ciprofloxacin.

‘There are some days when I just don’t want to be here,’ he says. ‘I never would have taken ciprofloxacin had someone explained the risks to me.’

As well as her physical symptoms, Lisa suffers with severe anxiety and insomnia. ‘Taking those few tablets have ruined my life,’ she says.

In a statement, Bayer, the main producer of ciprofloxacin, said patient safety is the company’s highest priority and ‘therefore we fully support the advice for healthcare professionals to be alert to the risk of psychiatric reactions when treating patients with fluoroquinolone antibiotics, of which ciprofloxacin is one such treatment.

‘These psychiatric reactions may occur after first administration of ciprofloxacin. If depression, psychotic reactions, suicide-related thoughts or behaviour occur, ciprofloxacin should be discontinued. The overall benefit-risk profile of Bayer’s fluoroquinolones remains unchanged and positive if used as directed’.

An MHRA spokesperson said there have been no drug safety updates on doxycycline (subsequent to the 2019 inquest). ‘We urge healthcare professionals and patients to continue to consult the advice in the product information regarding medicines safety including the Patient Information Leaflet.’

A spokesman for the British Generic Manufacturers Association said: ‘Our member companies take extremely seriously the safety in use of the generic medicines they market.

‘Under the legal requirements of their Marketing Authorisations issued by MHRA they regularly update their product information, including patient information leaflets, whenever requested to do so by the regulator.’

quintoxsupport.co.uk