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.

By MATTHEW LEEMING FOR THE DAILY MAIL – PUBLISHED: 17:42 EDT, 23 September 2019 | UPDATED: 03:27 EDT, 24 September 2019

In Tiny Doses, An Addiction Medication Moonlights As A Treatment For Chronic Pain

Lori Pinkley, a 50-year-old from Kansas City, Mo., has struggled with puzzling chronic pain since she was 15.

She’s had endless disappointing visits with doctors. Some said they couldn’t help her. Others diagnosed her with everything from fibromyalgia to lipedema to the rare Ehlers-Danlos syndrome.

Pinkley has taken opioids a few times after surgeries but says they never helped her underlying pain.

“I hate opioids with a passion,” Pinkley says. “An absolute passion.”

Recently, she joined a growing group of patients using an outside-the-box remedy: naltrexone. It is usually used to treat addiction, in a pill form for alcohol and as a pill or a monthly shot for opioids.

As the medical establishment tries to do a huge U-turn after two disastrous decades of pushing long-term opioid use for chronic pain, scientists have been struggling to develop safe, effective alternatives.

When naltrexone is used to treat addiction in pill form, it’s prescribed at 50 mg, but chronic-pain patients say it helps their pain at doses of less than a tenth of that.

Low-dose naltrexone has lurked for years on the fringes of medicine, but its zealous advocates worry that it may be stuck there. Naltrexone, which can be produced generically, is not even manufactured at the low doses that seem to be best for pain patients.

Instead, patients go to compounding pharmacies or resort to DIY methods — YouTube videos and online support groups show people how to turn 50 mg pills into a low liquid dose.

Some doctors prescribe it off-label even though it’s not FDA-approved for pain.

University of Kansas pain specialist, Dr. Andrea Nicol has recently started prescribing it to her patients, including Pinkley. Nicol explains that for addiction patients, it works by blocking opioid receptors — some of the brain’s most important feel-good regions. So it prevents patients from feeling high and can help patients resist cravings.

At low doses of about 4.5 mgs, however, naltrexone seems to work completely differently.

“What it’s felt to do is not shut down the system, but restore some balance to the opioid system,” Nicol says.

Some of the hype over low-dose naltrexone has included some pretty extreme claims with limited research to back them, like using it to treat multiple sclerosis and neuropathic pain or even using it as a weight-loss drug.

In the past two years, however, there’s been a big increase in new studies published on low-dose naltrexone, many strengthening its claims as a treatment for chronic pain, though most of these were still small pilot studies.

Dr. Bruce Vrooman, an associate professor at Dartmouth’s Geisel School of Medicine, was an author of a recent review of low-dose naltrexone research. Vrooman says that when it comes to treating some patients with complex chronic pain, low-dose naltrexone appears to be more effective and well-tolerated than the big-name opioids that dominated pain management for decades.

“Those patients may report that this is indeed a game changer,” Vrooman says. “It may truly help them with their activities, help them feel better.”

So how does it work? Scientists think that for many chronic pain patients, the central nervous system gets overworked and agitated. Pain signals fire in an out-of-control feedback loop that drowns out the body’s natural pain-relieving systems.

They suspect that low doses of naltrexone dampen that inflammation and kick-start the body’s production of pain-killing endorphins — all with relatively minor side effects.

Despite the promise of low-dose naltrexone, its advocates say few doctors know about it.

The low-dose version is generally not covered by insurance, so patients typically have to pay out of pocket to have it specially made at compounding pharmacies.

Advocates worry that the treatment is doomed to be stuck on the periphery of medicine because, as a 50-year-old drug, naltrexone can be made generically.

Patricia Danzon, a professor of health care management at the Wharton School at the University of Pennsylvania, explains that drug companies don’t have much interest in producing a new drug unless they can be the only maker of it.

“Bringing a new drug to market requires getting FDA approval and that requires doing clinical trials,” Danzon says. “That’s a significant investment, and companies — unsurprisingly — are not willing to do that unless they can get a patent and be the sole supplier of that drug for at least some period of time.”

And without a drug company’s backing, a treatment like low-dose naltrexone is unlikely to get the big promotional push out to doctors and TV advertisements that have turned drugs like Humira or Chantix into household names.

“It’s absolutely true that once a product becomes generic, you don’t see promotion happening, because it never pays a generic company to promote something if there are multiple versions of it available and they can’t be sure that they’ll capture the reward on that promotion,” Danzon says.

The drugmaker Alkermes has had huge success with its exclusive rights to the extended-release version of naltrexone, called Vivitrol. In a statement for this story, the company says it hasn’t seen enough evidence to support the use of low-dose naltrexone to treat chronic pain and therefore is remaining focused on opioid addiction treatment.

Pinkley says she is frustrated that there are so many missing pieces in the puzzle of understanding and treating chronic pain, but she, too, has become a believer in naltrexone.

She has been taking it for about a year now, at first paying $50 a month out of pocket to have the prescription filled at a compounding pharmacy. In July, her insurance started covering it.

“I can go from having days that I really don’t want to get out of bed because I hurt so bad,” she says, “to within a half-hour of taking it, I’m up and running, moving around, on the computer, able to do stuff.”

This story is part of NPR’s reporting project with KCUR and Kaiser Health News.

This story is part of NPR’s reporting project with KCUR and Kaiser Health News.