How everyday ibuprofen pills can help beat depression
Antidepressants don’t work for a THIRD of patients. But now doctors have identified a surprise new treatment ...
GO TO your GP complaining of depression and you’re likely to walk away with a prescription for an antidepressant. However, you might need two or three more different prescriptions before you eventually find the medication that works for you.
And even if it does, the benefits may well be little better than a placebo — and along the way you are likely to experience some unpleasant side-effects, such as drowsiness, nausea, insomnia and loss of libido.
But psychiatrists are increasingly confident that, within a few years, things could be very different, with patients being tested to find out whether a drug is likely to work for them. Their prescription would then be a drug cocktail tailored to their specific biology — and that cocktail might include an antiinflammatory drug such as ibuprofen.
What is driving these changes is a radical new theory about a cause of depression. For decades, psychiatrists had suggested it was due to a brain chemical imbalance: treatment was aimed at restoring this balance, usually by boosting levels of the mood chemical serotonin.
This ignored the emerging evidence that around 30 to 40 per cent of people with depression also had chronically raised levels of inflammation in their brains. Recent research has indicated that this can reduce the effectiveness of the mood-boosting pills.
Last year, Carmine Pariante, a professor of biological psychiatry at King’s College London, showed that measuring the level of two markers for inflammation in the blood could accurately predict if a depressed patient would benefit from the standard antidepressants, known as SSRIs (selective serotonin reuptake inhibitors), such as Prozac.
‘We found that above a certain level of inflammation, there was not going to be any benefit,’ he says.
This could make a significant difference to patients. ‘Half of all patients with depression fail to find an effective drug with their first prescription,’ says Professor Pariante, ‘and a third don’t benefit from any of them.’ WHen
a patient doesn’t respond to an antidepressant, doctors commonly increase the dose. But Professor Pariante’s research suggests something else might be more effective.
‘If inflammation levels are too high, an anti-inflammatory drug may help,’ he says. ‘We are testing one commonly used to treat acne, an antibiotic called minocycline.’
Paying attention to inflammation also promises to change the way we think about depression generally. ‘It makes depression just a part of what is going on in the whole body,’ explains Professor Pariante.
‘Patients seem to instinctively understand this, because they are very aware of the physical feelings that come with depression.
‘The aches and pains and the feeling of being sick and tired can be just like flu. That’s because inflammation is a sign of increased activity by the immune system.’
Most chronic diseases, such as heart disease, diabetes, cancer and Alzheimer’s, involve inflammation. It is the swelling and redness you see when you cut your finger or catch flu.
In the short-term, inflammation is protective, but in the long-term it becomes damaging.
‘Inflammation makes depression worse in several ways,’ says Professor Pariante. One is by raising production of damaging free radicals — these are a normal by-product of energy production but in excess, they affect the signals between different parts of the brain.
Inflammation also brings down levels of various chemical messengers in the brain that can improve your mood, such as serotonin, dopamine and endorphins, which have opium-like effects.
But new research shows it also affects a much less familiar, excitatory brain chemical called glutamate — depressed patients have been found to have high levels of glutamate and it has been shown to alter the flow of signals between brain cells.
exactly how this causes depression isn’t yet clear, but recent research has found that blocking it with a tranquilliser called ketamine, normally used on horses, can have a dramatic effect on long- term depression and suicidal thoughts. nearly half of a group of 100 patients with severe depression given a ketamine injection once a week responded to treatment for the first time, according to a report in April from the Oxford Health nHS Foundation Trust.
Understanding inflammation has led to another test for spotting patients who will or won’t respond to treatment. That is because inflammation can alter the way depressed people see life.
‘The technical term is “negative bias”,’ explains Catherine Harmer, a professor of cognitive neuroscience at Oxford University. ‘In daily life, these patients put a pessimistic spin on what people say or their facial expressions.
‘But they are not just naturally grumpy — we have shown it’s an effect of inflammation.’ This ‘negative bias’ phenomenon is a way of spotting those who will respond to medication, because an antidepressant works in patients with inflammation by making them more optimistic, an effect that happens fast.
Professor Harmer tests their response with a series of pictures of faces with different emotions.
‘At first, they see them as being more negative than a healthy person would. But within a week or so of taking the drug, some are seeing them in a more positive light, long before other signs of depression start changing.’
The test is now being trialled in a major study involving five countries in the eU.
So, why do people’s brains become inflamed in the first place? A major factor is stress, according to Philip Cowen, a professor of psychopharmacology at Oxford University and a clinical scientist with the Medical Research Council. ‘ Stress fires up the immune system and releases the hormone cortisol,’ he says. ‘That raises inflammation in the brain and around the body.
‘Doctors already routinely test inflammation levels in, for example, cancer, Crohn’s disease and rheumatoid arthritis, so it could easily be done for depressed patients. That would show who might benefit from existing anti-inflammatory drugs.’
These range from standard painkillers such as aspirin and ibuprofen — the so- called nonsteroidal anti-inflammatory drugs ( nSAIDs) — to heavyweight rheumatism drugs.
‘ I wouldn’t recommend you take them without a doctor being involved, but trying a natural anti- inflammatory, such as omega 3 in fish oil capsules, would be unlikely to cause a problem,’ says Professor Cowen. ‘You’d need to be getting at least a gram of the ePA essential fatty acid it contains.’ THAT
depressed patients with chronic inflammation are likely to have raised cortisol from stress means that relaxation therapies such as yoga and meditation might also be helpful to them. So, too, might probiotics.
The inflammation connection with depression is still at the research stage, and clinical trials are needed.
even so, it is already encouraging some researchers to experiment with combining drugs that affect the various mood-changing brain chemicals, such as dopamine and endorphins, rather than just targeting serotonin with SSRIs.
This is because one of the effects of inflammation is to alter the levels of all these brain chemicals.
Bringing in inflammation doesn’t just hold out the hope of a new, improved toolbox, but of seeing depression in a new light — not as a mysterious mind malfunction, but something as physical as arthritis or heart disease.
And that could be the biggest change of all.