Depression is one of those words we throw around without thinking too carefully about what it actually means or what its causes might be. Is it really appropriate to say that we are “depressed” because someone is late for an appointment or because the central heating has broken down? We have a wonderfully rich English language, and I think we should use it to the full.
To me, genuine depression is something much deeper. It can involve losing control of your emotions and feeling isolated and apart from your fellow human beings, with no one you feel able to reach out to. You don’t feel understood. You may even begin to wonder about the meaning of life. At some level you may know that life has meaning, but somehow that knowledge isn’t getting through to you psychologically or emotionally.
I find myself subject to ups and downs, and in my case they are often associated with not having, as I would put it, a pot on the boil—not having constructive things to do that excite and engage me. I need something to look forward to, something that stimulates me and gives me a sense of purpose. Perhaps this gives me a tiny glimpse into why solitary confinement must be so extraordinarily difficult for a human being.
I can also become downhearted when I contemplate the state of the world. There is a particular frustration in feeling powerless to do anything while watching what seems to me like a slow-motion destruction derby taking place before my eyes. I see politicians making statements I don’t believe, and institutions in which I once had greater confidence—the Church, the police, the judicial system, the Home Office, and border control—appearing increasingly compromised.
Whether one agrees with my assessment or not, the underlying question interests me: how much does our perception of the world around us affect our own state of mind? And, equally importantly, how do we prevent legitimate concern about the world from overwhelming our ability to live constructively within it?
I think depression is therefore a subject well worth exploring, and I intend to return to it on more than one occasion.
This morning I heard a BBC programme dealing with hard-to-treat depression. Inevitably, one programme cannot cover every aspect of such a complex subject, but I thought it provided a useful starting point for thinking and talking about it.
You might like to have a read. Ed.
Depression—perhaps we have been asking the wrong question.
I listened to a fascinating edition of BBC Radio 4’s All in the Mind dealing with what is called “hard-to-treat depression.” What interested me was not simply the various new treatments being investigated, but a much more fundamental question that ran through the whole program. What exactly do we mean when we use the word depression?
The program began with Professor Barney Dunn, professor of clinical psychology at the University of Exeter, who runs an NHS psychological therapy service dealing with people whose depression has proved difficult to treat. He was asked the obvious question: what does “hard-to-treat depression” actually mean? His answer was straightforward. It means that you remain depressed, or your depression rapidly returns after you have tried the treatments that would normally be offered. You may have tried several antidepressants and perhaps several forms of psychotherapy and yet you are still depressed.
The surprising figure was that this may apply to at least 30% of people with depression. Dunn made the interesting observation that when someone reaches this stage, perhaps the objective has to change somewhat. Instead of endlessly pursuing the idea of completely curing the depression, we may also need to help people learn how to live well alongside it.
A woman called Katie provided the human reality behind all this. She first experienced depression when she was 14 and is now 41. She had tried various antidepressants. The first actually made her feel worse; others helped but produced physical side effects. She now takes what she calls a maintenance dose, which “takes the edge off things” without solving everything. Cognitive behavioral therapy helped her understand the connection between her thoughts and feelings, but she did not feel that it ultimately enabled her to live the life she wanted.
Her description of depression struck me. She said that it “sucks the joy out of your life.” You can know perfectly well that there are things you normally love doing, yet find yourself unable to derive pleasure from them. There can also be physical exhaustion and a profound sense of isolation and disconnection from the world.
There is evidently also a considerable hole in our mental health system. At one end you have your GP, antidepressants, and NHS talking therapies, generally aimed at mild-to-moderate depression and anxiety. At the other end are specialist mental-health services for people who are severely ill or at significant risk. But what happens to the people in between? Katie found herself discharged from secondary mental health services while still struggling considerably, yet no longer eligible for primary care services. Dunn acknowledged that this gap is very real.
Are we making the same mistake with depression that we once made with fever?
For me, the most thought-provoking contribution came from Professor Ed Bullmore, author of The Inflamed Mind. He questioned whether “depression” itself is really an adequate diagnosis.
He used a wonderful analogy. Imagine going to a doctor in the 19th century with a high temperature and various other symptoms. The doctor might diagnose you as having a fever. Today that would not be enough. Fever is not really an explanation of what is wrong with you; it is a symptom. The doctor would want to discover whether your fever was caused by influenza, pneumonia, an infection, or something else entirely. Different causes require different treatments.
Bullmore wonders whether psychiatry is still at the “fever” stage in its understanding of depression.
At present we collect together a number of symptoms—disturbed sleep, changes in appetite, low mood, lack of activity, inability to experience pleasure, and so on—and if enough boxes are ticked, the person receives a diagnosis of depression. But what if two people who both satisfy those criteria have arrived there through completely different routes?
This seems to me enormously important. Perhaps asking somebody “Do you have depression?” will eventually seem as crude as asking somebody “Do you have a fever?” The more useful question is, why are you depressed?
Inflammation and the brain
One possible answer, at least for some people, may involve inflammation.
Bullmore explained that when he was a medical student in the 1980s, he was taught that the brain was essentially isolated from the immune system by the blood-brain barrier. Science has moved considerably since then. We now know that the nervous and immune systems communicate with one another continually and that the immune system itself has an important role in brain development.
Could inflammation therefore cause depression in some people? The answer appears to be possibly yes, but we are not yet at the point where this can simply be translated into routine treatment.
One trial of an anti-inflammatory drug did not show a significant improvement when researchers looked at the patients’ overall depression scores. But when they examined individual symptoms, something interesting emerged. There was a significant improvement in anhedonia.
This was a new word for me and an important one. Anhedonia means the inability to experience pleasure. Things that once delighted you simply don’t anymore. It is not necessarily sadness. It is the absence of joy.
This distinction could turn out to matter enormously. Instead of saying, “Here is a drug for depression,” perhaps medicine will eventually say, “Here is a treatment for this particular mechanism, which is preventing you from experiencing pleasure.”
There is already another interesting example. Dunn mentioned a drug called pramipexole, originally used for Parkinson’s disease. It acts upon the dopamine system involved in movement and reward, and there is evidence that it can help with anhedonia in some people with hard-to-treat depression.
It is not enough to remove misery.
This brought the program to what I thought was another profound point. People suffering from depression don’t necessarily want merely to feel less bad. They want to feel good again.
There is a difference.
Traditional treatments may be quite effective at reducing anxiety, sadness, and negative thinking without necessarily restoring enthusiasm, interest, pleasure, meaning, and purpose.
Dunn and his colleagues have therefore been developing something called ADEPT—Augmented Depression Therapy. The starting point is beautifully simple. Instead of concentrating entirely on what is wrong, the therapist asks the person something like, “If depression wasn’t dominating your life, what would you like your life to contain?”
It might be work, friendships, hobbies, relationships, looking after yourself or simply getting outdoors.
The person then begins moving towards those things while learning to recognize the ways in which depression tries to stop them. Dunn described certain thoughts as “dampening appraisals”: I don’t deserve this. I shouldn’t be enjoying myself. This isn’t good enough. I’ll be too big for my boots.
Rather than arguing endlessly with these thoughts, the person learns to notice them, step away from them, and return their attention to the experience itself.
Katie had undergone ADEPT and said something that stayed with me. Previously she had regarded recovery almost as an on/off switch. First I must get well, and then I can enjoy life.
ADEPT taught her something different: you can experience moments of joy while you are still unwell.
Her father was undergoing cancer treatment at the time, so objectively it was an extremely difficult period of her life. Nevertheless, she deliberately began noticing the things that still gave her pleasure—nature, walking her dog, and going down to the beach.
And the achievement does not have to be enormous. On a particularly difficult day it might simply be getting out of bed and making yourself a nice cup of tea.
I thought that was perhaps one of the wisest observations in the whole programme.
Putting a small electrical current through the brain
Then we came to something completely different — transcranial direct current stimulation, or TDCS.
This involves wearing a headset with electrodes positioned against the forehead through which a very small electrical current is passed. The presenter tried it herself and described some tingling and itching but nothing particularly unpleasant.
Professor Cynthia Fu of King’s College London explained the theory. Depression appears to involve alterations in the way different brain circuits communicate, including circuits concerned with mood, memory and concentration. Some areas may be underactive and others overactive. By slightly altering the electrical activity of one region, TDCS may influence the wider circuit.
The current involved is tiny — about two milliamps in the treatment described. Fu compared this with approximately 200 milliamps involved in operating an ordinary torch. It is also quite different from electroconvulsive therapy. It does not produce a seizure and doesn’t require an anaesthetic.
In the study described, people used the equipment for about half an hour at a time over ten weeks, initially around five times a week and later around three. This isn’t a case of putting the headset on for half an hour and suddenly feeling wonderful. Any improvement appears to develop gradually over a period of weeks.
Perhaps most interestingly, the treatment can be administered at home under clinical supervision. During the pandemic researchers discovered that they could supervise people’s first sessions through video calls rather than having somebody physically present.
The evidence is not uniform. It appears promising for some people whose depression has not responded adequately to antidepressants, but results are more mixed among people who have been through many different antidepressants over many years. Once again we return to the same conclusion: depression is not one thing.
The combination lock
Towards the end Dunn produced another analogy which I liked.
He described depression as a biological, psychological and social beast. There might be something biological happening in the brain or body. There might be particular habits of thought. And there may be circumstances in someone’s life which are continually reinforcing the problem.
He compared this to a combination lock.
There may not be one magic number which opens it. You have to discover the right number for each part of the lock.
This also explains why the future may lie not in discovering the cure for depression but in intelligently combining treatments. Medication might help one element, psychological therapy another, changes in circumstances another, and perhaps treatments such as tDCS another.
Other possibilities currently being researched include ketamine, psychedelics and even altering the bacteria in the gut.
The eventual destination is something called precision psychiatry. Instead of treating everybody carrying the same label in roughly the same way, doctors would try to establish the particular biological, psychological and social factors which are triggering and maintaining depression in this particular human being.
We are apparently still some distance from that ideal, but the direction of travel seems sensible to me.
There are now 15 research clinics across England, Scotland and Wales concerned with hard-to-treat depression, and interestingly people can refer themselves rather than necessarily having to go through their GP. They can receive specialist assessment and may also have the opportunity to participate in trials of some of these newer approaches.
A couple of moments of joy
The programme ended where perhaps it should have begun — with Katie rather than the professors.
After living with depression for many years she has become better at recognising when it is returning and knowing what she can do about it. But the most valuable thing she has learned is not to wait until everything is right before allowing herself to experience something good.
There may be days when almost everything seems black and there are only two small moments of joy.
Notice them.
Hold onto them.
And then build upon them.
Perhaps depression is not one disease at all but the final common destination of many different roads. If so, the great mistake may have been assuming that everyone arriving at that destination should be given the same map for the journey home.
