Antidepressants are among the most commonly prescribed drugs throughout the western world. In fact, they are prescribed more than any other drug for Americans aged 18 to 44, and they are now taken four to five times more frequently than in the early 90s. In the UK, antidepressant use has doubled over the past decade. Either more people are depressed, more people are talking about their depression, or doctors now think they have got a pill that will help.
What are these drugs? Unlike the antidepressants of 30 years ago, they are considered “clean” and well-tailored. They target a certain neurochemical and leave the rest of the brain alone. (Old-school antidepressants were notorious for their scattershot effect.)
First-line antidepressants are almost exclusively what are called selective serotonin reuptake inhibitors (SSRIs), with the emphasis on “selective”. That means they keep serotonin in the connections between neurons (the synapses, where all the action is) far longer than it would normally remain. Serotonin is a neurochemical that appears to moderate the information travelling between neurons. The theory is that depression grows from too much information, consisting mainly of self-criticism, negative memories and negative expectations, cycling in an endless loop. More serotonin should diminish this unhelpful deluge.
But do SSRIs actually work? Despite great promise, the big picture reveals a mixed bag of results – and opinions. Many studies have revealed extremely limited effectiveness for SSRIs when compared with placebos. These disappointing results drew attention to studies conducted by the pharmaceutical companies, in which poor results were systematically buried. (Did we really trust the drug makers to present an unbiased picture?) Yet other well-controlled studies suggest that SSRIs do help depressed people at least some of the time. The final verdict? SSRIs help some people on a good day, according to some studies and not others. Most experts agree that it would be a very good thing to find other drugs that work more reliably.
Along comes ketamine. Ketamine has been around since the early 1960s, when it became available as an anaesthetic for use with humans and animals. Its psychotropic (mind-altering) effects were soon discovered. Ketamine changed people’s perception of themselves and the world around them to a degree comparable to LSD and other psychedelics. Thus began its career as a street drug and its designation as a controlled substance. You know how the reasoning goes: we can’t let people go around changing their reality. Nevertheless, it has been used as a party drug for decades, often under the nickname “K”.
Ketamine’s potential for fighting depression has been studied for years. Current reviews conclude that it is highly effective against depression – a promising new medicine, but potentially dangerous, both physically (you can lose your balance) and psychologically (it can produce psychotic-like states). But how does it work?
The main neurotransmitter for communicating between brain cells is glutamate. Little bundles of glutamate molecules, sent from one neuron to the next, tell each neuron how rapidly to fire – a very important message. But glutamate molecules have to enter the receiving cell through a doorway designed to welcome them. And one of the main doorways is called the NMDA receptor.
Thanks to swarms of glutamate molecules shooting into NMDA receptors all over the brain, an incredibly complex, incredibly subtle network of firing neurons creates our sense of reality. When the brain is functioning normally, the pattern of firing neurons matches what is going on in the world outside your brain. If you happen to be schizophrenic, then not so much.
What ketamine does is block many of those NMDA receptors, so the glutamate molecules have nowhere to land. Consequently, the network that fashions reality starts to fall apart. The harmony of synchronised neurons breaks down, and your perception of the world starts to drift. That’s why ketamine is called a “dissociative”. Ketamine has been used on the battlefield where wounded soldiers can dissociate from their pain. So ketamine’s main contribution is to free you from what’s in front of your face.
Nobody knows exactly how ketamine nails depression. Yet I don’t think it’s so mysterious. When people are depressed, they undergo the same cycling thought patterns over and over again: I’m no good. Nobody really likes me. I don’t deserve to be happy. I’m too selfish, too greedy, too unpleasant. It’s called rumination. What’s more, the negative self-thoughts reinforced through rumination promote feelings of sadness, shame and hopelessness, while those feelings reinforce the spiralling negative thoughts. A vicious circle indeed.
What ketamine might do is break the cycle, perturb the relentless repetition of depressive self-appraisals. The “reality” that you are a bad, worthless person gets fragmented, because ketamine fragments everything you think you know. Ketamine permits you to sojourn into different psychological realities. That is one of the risks associated with clinically dispensed ketamine, but for depressives, a little holiday from the daily grind of pessimism might be a welcome relief.
It would be great if ketamine-based treatment moves beyond its interminable research phase: is it really safe? Can we be absolutely sure? Let’s not forget that booze can also make you lose your balance, and it’s quite legal. And depression itself can generate psychosis, often for lengthy periods. Ketamine doesn’t look so bad on balance.
I would like to see ketamine become available, at least through the safeguards of the doctor-patient relationship, to the millions who suffer depression. But there is a lesson to be learned from ketamine’s protracted debut. We are so afraid of the drugs people take for fun, to feel good, or at least to feel different for a few hours, that we ban them almost reflexively and punish those who use them. Why? What’s so bad about adults taking a vacation from the imperious reality we call “normal” – a reality that, sorry to say, isn’t decreed by God or nature but by culture, by a semi-arbitrary history of conventions? We should divert some of our hyped-up fear of abuse potential into a societal experiment, a sandbox, so to speak, for exploring the benefits of various popular drugs – drugs (such as ketamine, marijuana, ecstasy and psilocybin) that are illegal because people sometimes want to take them. Surprise, surprise: these drugs might just help people feel better.
If ketamine helps treat depression, why can’t doctors prescribe it? | Marc Lewis
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