Is this proof depression can be a physical illness? MATTHEW LEEMING says he cured his depression with anti-inflammatory drugs
Having no money is ‘sick-making’, as Evelyn Waugh’s characters used to say.
At the age of 47 I found myself living in Dubai, broke after a business venture went horribly wrong, and pole-axed with treatment-resistant depression.
I couldn’t work I felt so awful. Getting out of bed and into a taxi to a friend’s office where I pretended to occupy myself each day was an ordeal.
It was 2012 and for 20 years I’d been on a type of antidepressant called a tricyclic which, until then, had kept the depression which had only once before rendered me unable to work, at bay.
But it stopped being effective, I think through the shock of the business problems.
Trying to explain what depression feels like is difficult because it is in part an absence: an absence of feeling, an absence of self-respect, a lack of power to do anything and be optimistic.
I know of someone who had suffered depression and cancer and who said depression was worse. ‘When I had cancer, I wanted to live. But when I had depression I wanted to die,’ they said.
The brain itself has no pain receptors but I think everyone with depression would agree that the disease is the mental equivalent of pain — concentrated anguish, unrelieved negative thoughts, hatred of oneself.
But you also feel physically ill, as if you had been hit by a train. It’s not that you can’t be bothered to get out of bed: it is as physically difficult to do so, as when you have flu.
Living with depression is like carrying a large weight around. That weight is heavier in the morning perhaps because in many depressed people levels of cortisol (a stress hormone) are higher in the morning.
The cortisol levels and feelings of illness suggested to me that depression might be a physical disease. Although I didn’t know about the cortisol link at the time, when I first saw a doctor about the depression I said: ‘This is physical.’
But it meant nothing to him. He probably took this thought to be another symptom. However, 20 years later, I read about the work of Carmine Pariante, a professor of biological psychiatry — a brand new discipline — at King’s College, London, which suggested depression can indeed be an inflammatory physical illness.
‘In some cases, depression is due to normal bodily processes going wrong, the product of a malfunctioning immune system,’ Professor Pariante told me.
At the heart of his case are two well-attested observations. The first is the effects of interferon, a drug that stimulates the immune system to use inflammation to destroy the hepatitis virus lodged inside the liver.
One study Professor Pariante was involved with, which was published in the journal Neuropsychopharmacology in 2016, found that a third of patients given interferon for hepatitis treatment developed depression, and these were the patients who had the strongest inflammation.
‘This suggests that the depression in these patients might be caused by the inflammation,’ says Professor Pariante.
Second, people with rheumatoid arthritis often become depressed. Rheumatoid arthritis is an auto immune condition that occurs when the immune system perceives the body’s chemical messengers as invading bacteria and secretes an inflammatory chemical, tumour necrosis factor (TNF), in a bid to destroy them resulting in join pain and swelling.
Around 20 per cent of patients with this disease are also depressed according to Edward Bullmore, a professor of psychiatry at the University of Cambridge. Most doctors regard the depression as a response to the misery of the disease. But Professor Pariante believes the TNF causes the depression. ‘We now know that chemicals secreted by the body to signal the increased inflammation, such as TNF, can also directly affect brain cells and brain function, inducing depressive symptoms,’ he explains.
An anti-inflammatory drug called Remicade, developed to treat rheumatoid arthritis, that blocks the action of TNF has been a remarkably effective treatment for the disease he says.
In some patients it also caused an apparently miraculous lifting of the patient’s depression. The effect can be so dramatic that nurses call it the ‘Remicade high’.
Remicade — also known as infliximab — was recently trialled as an antidepressant but was only shown to be effective for patients with both depression and high inflammatory markers.
However TNF is just one of many inflammatory proteins in our bodies and according to Professor Pariante the resulting inflammation they bring causes ‘sickness behaviour’, something our body does to rid itself of damaging viruses and toxins while the lethargy and lack of motivation gives it a chance to recover.
Increased inflammation can affect our emotions and behaviour and induce symptoms that resemble depression, such as fatigue, malaise, aches and pains, bad mood and reduced interest in socialising,’ Professor Pariante says. ‘If you remember how you felt last time you had a really bad infection, you will recognise these symptoms. In fact, inflammatory chemicals change the function of brain areas that are important for anxiety and depression.’
If Professor Pariante is right, the inflammation theory suggests that in many cases depression is your mind telling your body you are ill when you are not — you are actually suffering inflammation.
Not all depression is caused like this but Professor Pariante estimates that 40 per cent of cases may involve inflammation.
Professor Pariante’s work turned on a mental lightbulb for me. A professor agreed that my disease was physical!
And because I was living in Dubai I was able to do something about it. That’s because you can buy Celebrex, a non-steroidal anti-inflammatory used for treating arthritis, over-the-counter there (but only on prescription in the UK). Internet research following reading about Pariante’s work produced papers showing its clinical effectiveness when used with antidepressants.
So I bought a packet. I took 200mg a day (I guessed at the dose) for a week with no effect but then one evening I took 400mg, the dose prescribed daily for arthritis. Within half an hour the ghastly feelings were leaving me, the anxiety in my stomach contracting as if after a strong drink following a bad day at work. Within two weeks I stopped taking the antidepressants — for the first time in 20 years. I felt normal.
Chekhov (a doctor as well as a writer) once said ‘If many remedies are prescribed for an illness, you may be certain that the illness has no cure’ and there are certainly a huge number of antidepressants on the market, none of which are universally effective. But this could be because depression has a number of causes, one of which it seems is inflammation.
Professor Pariante says that ‘depression could be like a fever — a symptom of a variety of underlying pathologies’.
So what does this mean for treatment? Professor Edward Bullmore in his book The Inflamed Mind predicts that future research will involve investigating drugs like Remicade and Celebrex rather than looking for new antidepressants in the mould of Prozac.
But despite my positive experience with anti-inflammatories Professor Bullmore warns: ‘Doctors and psychiatrists will want to see positive clinical trial data before recommending anti-inflammatory treatment for depression.
‘It is worth remembering that all anti-inflammatory drugs, including Celebrex, have side-effects and it is not advisable to start taking them until the evidence for therapeutic benefit is clearer. Hopefully, there will be further progress in the next few years to get us to that point but the current situation is still a scientific work in progress.’
I don’t think patients should suffer while there are effective drugs much less dangerous than lithium — which is what is generally prescribed for treatment-resistant depression — available.
If Professor Pariante is right, people with depression may gain more than a new treatment. We may receive sympathy. The inflammation theory provides depressed people with an acknowledgement that they are physically ill and can’t just pick up their mat and walk.