Are your medications making you miserable? Over the past decade researchers have uncovered significant links between many of our most commonly used drugs – from over-the-counter indigestion remedies to heart pills – and patients taking them suffering depression.
Now, alarmingly, scientists are warning that blockbuster slimming jabs such as Wegovy, Ozempic and Saxenda may also carry a risk of depression – just as the Government is planning to put millions of Britons on such drugs (which are known as GLP-1 agonists).
In a study recently published in the journal Scientific Reports, based on eight years’ worth of data from more than 160,000 obese patients, those taking the slimming drugs had nearly treble the normal risk of depression and double the risk of anxiety – while their risk of suicidal behaviour was up to three times higher compared with people who weren’t on the drugs, reported researchers from Chung Shan Medical University in Taiwan.
Yi-Sun Yang, a professor of medicine who led the study, said: ‘This finding holds significant importance, noting that studies have typically excluded patients with a history of psychiatric disorders – resulting in a lack of data for understanding the long-term consequences of GLP-1 drug use in patients with obesity.’
In fact, depression is a worryingly common side-effect with a number of widely used prescription medicines.
Research in the Journal of the American Medical Association in 2018 found that more than a third of adults are taking medications known to carry a risk of causing depression as a side-effect. And the more types of medications someone takes, the higher their depression risk.
The researchers warned: ‘The use of prescription medications that have depression as a potential adverse effect is common and associated with greater likelihood of depression.’
Indeed recent research has highlighted this risk for numerous widely used medications, including those that treat acid reflux, such as omeprazole; beta-blockers such as atenolol; drugs used to treat high blood pressure and irregular heartbeats.
Rimonabant, an anti-obesity agent, was withdrawn from the market in 2008 due to depressive side effects
Other drugs linked to depression include some prescription-only antibiotics, steroids, Parkinson’s drugs and the Pill (more of which later).
And GLP-1s are not the first weight-loss drugs linked to psychiatric problems.
Rimonabant, an anti-obesity agent, was withdrawn from the market in 2008 due to these kinds of side-effects. Brand name Acomplia, it was launched by the French pharmaceutical company Sanofi-Aventis in 2006 in Europe, but its licence was withdrawn there after it was found to be causing an unacceptable level of psychiatric disorders, particularly depression.
In a letter to British healthcare professionals explaining the withdrawal, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) wrote: ‘There was approximately a doubling of the risk of symptoms such as depression, sleep disturbance, anxiety and aggression.’
Rimonabant acts as an appetite suppressant by inhibiting the release of hunger hormones in the brain. In 2010, a report in the journal Neurobiology of Disease by drug-maker Pfizer, which itself abandoned attempts to launch a similar type of slimming drug (called a cannabinoid receptor antagonist), said that the medication may cause depression because it also lowers levels of the ‘feelgood’ brain chemical serotonin and causes inflammation in the brain that might cause mood to plummet.
The MHRA letter said that the depressive side-effects of rimonabant may have been more common in clinical practice than in the clinical trials.
Could the same happen with the GLP-1 agonist drugs?
The researchers involved in the recent study in Scientific Reports suggest that GLP-1s may reduce levels of dopamine in the brains of some patients.
Weight loss drugs may reduce levels of dopamine, which prompts feelings of motivation and reward, in some patients
Low dopamine levels are linked with depression – possibly because dopamine prompts feelings of motivation and reward, so a shortage can cause people’s moods to plunge.
This latest study echoes the results from research last year, based on World Health Organisation data on reported side-effects – this showed that people who took semaglutide (the drug in Wegovy and Ozempic) were 45 per cent more likely to have thoughts of suicide or self-harm than people on other medications, reported the journal JAMA Network Open.
Numbers of such side-effects could rise as the Government announced in December that the GLP-1 drug Mounjaro (generic name tirzepatide) will be rolled out on the NHS in England to 3.5million Britons, starting this month: Mounjaro will be offered to people with a body mass index (BMI) of more than 35 and at least one obesity-related health problem.
The problem is that while many people clearly benefit from their medication, they may not realise it could also be raising their risk of depression. Or that it might be why they feel so low.
‘If you can associate the onset of your depressive feelings with starting the medicine, then that’s a strong sign it may be a side-effect,’ says Leyla Hannbeck, chief executive of the Independent Pharmacies Association.
Leyla Hannbeck, chief executive of the Independent Pharmacies Association, says you should not stop taking medication that you suspect is causing side effects without first consulting your doctor
However, she stresses: ‘Many of these medications can treat serious health problems. So if you feel depressive symptoms, you should not just stop taking them without first discussing this with your doctor, as having your meds swapped for similar prescribed ones may make a real difference.’
Here, we look at some of the other commonly prescribed medications with this worrying side-effect…
Heartburn drugs
People who regularly take proton-pump inhibitors (PPIs) to treat indigestion and heartburn have more than double the normal risk of developing depression, according to a study of more than 70,000 Americans’ health records, published in the journal Nature Scientific Reports in 2022.
PPI drugs suppress acid production in the stomach – around one in six UK adults take PPIs, according to a BMJ report in 2023.
Scientists have suggested various ways in which PPI drugs, which can also be bought over-the-counter, may cause depression.
They may interfere with proteins in nerves throughout the body and brain, raising the risk of neurological damage that can lead to depression and dementia, reported the journal Neural Plasticity in 2018.
Another study, in 2018, suggested that the psychological side-effects of PPIs are potentially caused by the reduced absorption of nutrients, especially vitamin B12 (stomach acid helps to break down food).
Vitamin B12 helps to maintain the neurological system and a deficiency may cause cognitive impairment and neurological disorders, according to researchers at Cardiff University.
Beta blockers
Beta blockers have been used for decades to treat patients after a heart attack – the drugs block the effects of adrenaline, causing the heart to beat more slowly and with less force, which in turn lowers blood pressure.
Beta blockers also help widen veins and arteries to improve blood flow. Numerous studies suggest that they may increase people’s risk of depression.
A study last November suggested that the patients most likely to suffer depression as a side-effect of beta-blocker drugs were also the least likely to benefit from taking them, reported the New England Journal of Medicine.
This found that many heart attack survivors don’t actually need to take beta blockers because their hearts’ pumping ability hasn’t been damaged. What’s more, these unnecessarily treated patients are the most likely to experience depressive symptoms as a result of taking the drugs.
Previously researchers have suggested various reasons for the link between beta blockers and depression.
One theory is that they interfere with the ‘feelgood’ brain chemical serotonin, or alternatively the pills may reduce the brain’s production of the hormone melatonin, also thought to cause depression, according to a 2022 paper in the journal Drug Safety.
The authors, led by Christoph Meier, a professor of pharmacology at the University of Basel in Switzerland, recommended that people with depression as a consequence of taking beta blockers may benefit from changing to another class of drugs called hydrophilic beta-blockers, which don’t penetrate the protective blood-brain barrier.
Steroids
Steroids are used widely to treat conditions such as arthritis, asthma, eczema and allergies, by lowering inflammation.
However, they have also been linked to symptoms of depression. In 2022, scientists at Leiden University Medical Centre in The Netherlands reported that this may be because they cause structural changes in the brain.
This was based on more than 750 UK patients who were taking the drugs long term – for months or years: they had a smaller amygdala, a region of the brain linked with the processing and regulation of emotions.
Other reasons have been suggested, including steroids reducing levels of the ‘feelgood’ chemical serotonin.
The pill
Women using birth-control pills may have as much as 130 per cent increased risk of depression, particularly in the first two years of taking them, according to a 2023 study in the journal Epidemiology and Psychiatric Sciences.
Based on the health records of more than 264,000 British women, this analysis showed the risk seemed to have disappeared within two years of women stopping birth control pills.
This echoes a previous study by the University of Copenhagen, based on more than one million Danish women’s health records and published in the journal JAMA Psychiatry in 2016.
It found that the longer a woman was prescribed a hormonal contraceptive, the greater her risk of being treated with antidepressant drugs for the first time.
Previous studies have suggested that the hormones in the Pill, particularly progesterone, may disrupt some women’s brain function in some way.
