Ketamine has ‘fast-acting benefits’ for depression

Ketamine has “shown promise” in the rapid treatment of major depression and suicidal thoughts, a US study says.

Ketamine has a reputation as a party drug but is licensed as an anaesthetic.

The study found use of the drug via a nasal spray led to “significant” improvements in depressive symptoms in the first 24 hours.

The Royal College of Psychiatrists said it was a “significant” study that brought the drug “a step closer to being prescribed on the NHS”.

The report by researchers from Janssen Research and Development, a Johnson and Johnson company, and Yale School of Medicine, is the first study into ketamine as a treatment for depression that has been done by a drug company.

It is being published in the American Journal of Psychiatry.

The trial looked at 68 people at imminent risk of suicide.

All patients were treated with a stay in hospital and anti-depressants.

In addition, half were given ketamine in the form of esketamine (part of the ketamine molecule) in a nasal spray and half were given a placebo.

The study found those using esketamine had a much greater improvement in depression symptoms at all points over the first four weeks of treatment.

However, at 25 days the effects had levelled out.

The study’s authors suggest it could offer an effective rapid treatment for people severely depressed and at imminent risk of suicide and could help in the initial stages of treatment, as most anti-depressants take four to six weeks to become fully effective.

The nasal spray is now undergoing phase three trials before it can be licensed for treatment.

Potential for abuse

There were no reports of esketamine dependence or misuse in the trial but the authors warn that more research is needed on the potential for abuse of ketamine and say these should be looked at during subsequent trials.

Scientists in the UK are also studying ketamine as a treatment for depression taken intravenously.

Dr James Stone, from the Royal College of Psychiatrists, told the BBC the “interesting” US study confirmed the findings from successful studies into intravenous ketamine.

“The main reason for its significance is because this is being developed by a drug company and it’s potentially quite likely that this medication might become available as a treatment available on the NHS for depression.”

‘Severe depression’

He said because it was being given as a nasal spray it was “much easier to administer” than intravenous ketamine and was “potentially quicker to give, so it means more people can be dosed at the same time” and you need less equipment.

Dr Stone said if it did go on to be prescribed on the NHS it would be aimed at people with severe depression as a second or third line of treatment if other drugs haven’t worked and could be used for people instead of electroconvulsive therapy.

Prof Mitul Mehta from King’s College told the BBC it was an “exciting” study.

“All the studies to date have been looking at intravenous use – there are some people who have explored oral ketamine but that doesn’t appear to be as successful as intravenous so intranasal seems to be a really good halfway-house.

“It enters the body relatively quickly – it’s not as fast as going straight into your bloodstream but not as slow as via the stomach and it’s reasonably easy to control how much you give to a person. In that respect this is a really important study.”

But he said far bigger studies are needed to look out for any rare side-effects.

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How bacteria are changing your mood

If anything makes us human it’s our minds, thoughts and emotions.

And yet a controversial new concept is emerging that claims gut bacteria are an invisible hand altering our brains.

Science is piecing together how the trillions of microbes that live on and in all of us – our microbiome – affect our physical health.

But even conditions including depression, autism and neurodegenerative disease are now being linked to these tiny creatures.

We’ve known for centuries that how we feel affects our gut – just think what happens before an exam or a job interview – but now it is being seen as a two-way street.

Groups of researchers believe they are on the cusp of a revolution that uses “mood microbes” or “psychobiotics” to improve mental health.

The study that ignited the whole concept took place at Kyushu University in Japan.

The researchers showed that “germ-free” mice – those that never came into contact with microbes – pumped out twice the amount of stress hormone when distressed than normal mice.

The animals were identical except for their microbes. It was a strong hint that the difference was a result of their micro-organisms.

“We all go back to that first paper for the first wave of neuroscientists considering microbes,” says Dr Jane Foster, a neuropsychiatrist at McMaster University in Canada.

“That really was very powerful for those of us who were studying depression and anxiety.”

It was the first hint of microbial medicine in mental health.

How could bacteria be altering the brain?

The brain is the most complex object in the known universe so how could it be reacting to bacteria in the gut?

  • One route is the vagus nerve, it’s an information superhighway connecting the brain and the gut.
  • Bacteria break down fibre in the diet into chemicals called short-chain fatty acids, which can have effects throughout the body.
  • The microbiome influences the immune system, which has also been implicated in brain disorders.
  • There is even emerging evidence that gut bugs could be using tiny strips of genetic code called microRNAs to alter how DNA works in nerve cells.

    There is now a rich vein of research linking germ-free mice with changes in behaviour and even the structure of the brain.

    But their completely sterile upbringing is nothing like the real world. We’re constantly coming into contact with microbes in our environment, none of us are germ-free.

    At Cork University Hospital, Prof Ted Dinan is trying to uncover what happens to the microbiome in his depressed patients.

    A good rule of thumb is a healthy microbiome is a diverse microbiome, containing a wide variety of different species living all over our bodies.

    Prof Dinan says: “If you compare somebody who is clinically depressed with someone who is healthy, there is a narrowing in the diversity of the microbiota.

    “I’m not suggesting it is the sole cause of depression, but I do believe for many individuals it does play a role in the genesis of depression.”

    And he argues some lifestyles that weaken our gut bacteria, such as a diet low in fibre, can make us more vulnerable.

    The microbiome

    • You’re more microbe than human – if you count all the cells in your body, only 43% are human
    • The rest is our microbiome and includes bacteria, viruses, fungi and single-celled archaea
    • The human genome – the full set of genetic instructions for a human being – is made up of 20,000 instructions called genes
    • But add all the genes in our microbiome together and the figure comes out at between two million and 20 million microbial genes
    • It’s known as the second genome and is linked to diseases including allergy, obesity, inflammatory bowel disease, Parkinson’s, whether cancer drugs work and even depression and autism

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      It’s an intriguing concept – that an imbalance in the gut microbiome could be involved in depression.

      So scientists at the APC Microbiome centre, at University College Cork, started transplanting the microbiome from depressed patients to animals. It’s known in the biz as a trans-poo-sion.

      It showed that if you transfer the bacteria, you transfer the behaviour too.

      Prof John Cryan told the BBC: “We were very surprised that you could, by just taking microbiome samples, reproduce many of the features of a depressed individual in a rat.”

      This included anhedonia – the way depression can lead to people losing interest in what they normally find pleasurable.

      For the rats, that was sugary water they could not get enough of, yet “when they were given the microbiome from a depressed individual, they no longer cared”, says Prof Cryan.

      Listen to The Second Genome on BBC Radio 4.

      The next episode airs at 11:00 BST on Tuesday April 24, repeated 21:00 BST Monday April 30 and on the BBC iPlayer

      Similar evidence – linking the microbiome, the gut and the brain – is emerging in Parkinson’s disease.

      It is clearly a brain disorder. Patients lose control over their muscles as brain cells die and it leads to a characteristic tremor.

      But Prof Sarkis Mazmanian, a medical microbiologist from Caltech, is building the case that gut bacteria are involved.

      “Classical neuroscientists would find this as heresy to think you can understand events in the brain by researching the gut,” he says.

      He has found “very powerful” differences between the microbiomes of people with Parkinson’s and those without the disease.

      Studies in animals, genetically hardwired to develop Parkinson’s, show gut bacteria were necessary for the disease to emerge.

      And when stool was transplanted from Parkinson’s patients to those mice, they developed “much worse” symptoms than using faeces sourced from a healthy individual.

      Prof Mazmanian told the BBC: “The changes in the microbiome appear to be driving the motor symptoms, appear to be causal to the motor symptoms.

      “We’re very excited about this because it allows us to target the microbiome as an avenue for new therapies.”

      The evidence linking the microbiome and the brain is as fascinating as it is early.

      But the pioneers of this field see an exciting prospect on the horizon – a whole new way of influencing our health and wellbeing.

      If microbes do influence our brains then maybe we can change our microbes for the better.

      Can altering the bacteria in Parkinson’s patients’ guts change the course of their disease?

      There is talk of psychiatrists prescribing mood microbes or psychobiotics – effectively a probiotic cocktail of healthy bacteria – to boost our mental health.

      Dr Kirsten Tillisch, at University of California, Los Angeles, told me: “If we change the bacteria can we change the way we respond?

      But she says we need far bigger studies that really probe what species, and even sub-species, of bacteria may be exerting an effect on the brain and what products they are making in the gut.

      Dr Tillisch said: “There’s clearly connections here, I think our enthusiasm and our excitement is there because we haven’t had great treatments.

      “It’s very exciting to think there’s a whole new pathway that we can study and we can look and we can help people, maybe even prevent disease.”

      And that’s the powerful idea here.

      The microbiome – our second genome – is opening up an entirely new way of doing medicine and its role is being investigated in nearly every disease you can imagine including allergies, cancer and obesity.

      I’ve been struck by how malleable the second genome is and how that is in such stark contrast to our own DNA.

      The food we eat, the pets we have, the drugs we take, how we’re born… all alter our microbial inhabitants.

      And if we’re doing that unwittingly, imagine the potential of being able to change our microbiome for the better.

      Prof Cryan said: “I predict in the next five years when you go to your doctor for your cholesterol testing etc, you’ll also get your microbiome assessed.

      “The microbiome is the fundamental future of personalised medicine.”

      Follow James on Twitter.

      Illustrations: Katie Horwich

Could you be a workaholic, addicted to your job?

“My name is JC and I am a workaholic.”

JC, who lives in Tampa Bay, Florida, says she needed a lot of courage the first time she stood up and said that in front of a group of people she had never met before.

JC, who doesn’t want us to reveal her full name, had gone along to a meeting of Workaholics Anonymous because she felt she couldn’t cope anymore.

A 40-year-old healthcare worker, who had conquered her alcoholism and an eating disorder, she says she couldn’t experience the serenity that she hoped sobriety would bring because she instead had become addicted to working.

“I was constantly obsessed with work,” she says. “I realised I used work to numb out and avoid myself, my feelings and my fears.”

Her work addiction and the stress that came with it affected her health.

“I had premature grey hair within three months of starting a management position,” she says. “I experienced adrenal fatigue… I have a heart condition.”

Following a similar 12-step recovery plan to the one first devised by Alcoholics Anonymous, Workaholics Anonymous started in the US in the early 1980s.

Today there are more than 100 meeting groups around the world, from Argentina to the US, the UK and Japan. There is also the possibility of joining an online meeting via Skype or over the phone.

But how do you know if you are a workaholic? And what other ways are there to get help?

Wilmar Schaufeli, a professor of work and organisational psychology at Utrecht University in the Netherlands, describes a workaholic as “a person who works obsessively hard in a compulsive way”.

“So it’s a combination between excessive work and compulsive work, compulsive tendency.”

He adds that going to Workaholics Anonymous works for many sufferers because “you see people who have the same problem, so you are not alone. I think this is an important thing for all kinds of behavioural problems or addictions.”

For other people with work addiction problems, having one-to-one therapy with a trained professional might be the answer.

But what actually can lead to work addition?

Dr Claudia Herbert, a clinical psychologist at the Oxford Development Centre, in Putney, Oxfordshire, often treats sufferers. She says that many workaholics have other mental health disorders.

“Lots of clients may feel depressed, they may actually think that life is a little bit empty, they may have anxiety problems, they may also have addictions to cope with.”

The condition can be triggered by someone having to work too hard in the first place. “People often have to take jobs that in previous times would have been done by two or three people,” she says.

Work addiction may be caused in part by a person being pushed too hard by his or her parents in their earlier life. “People who as children were reinforced by their achievements rather than who they are, they are more likely to become work addicted,” she adds.

When it comes to the types of jobs where people are more vulnerable to becoming workaholics, Prof Schaufeli says it is more a case of senior professionals rather than those with jobs on the lower rungs of the workplace ladder.

He says that self-employed people are also vulnerable because they can become obsessed by their businesses.

Prof Schaufeli adds that work addicts very often don’t see that their behaviour is problematic because the fact they are doing vast amounts of work often means they are earning more and being promoted.

When it comes to treating work addiction, Dr Herbert says it needs to be individually tailored to each sufferer, and getting to the bottom of what caused it.

At Retreat South, a rehabilitation centre and mental health retreat in the Australian state of Victoria, they run a work-related stress and executive burnout programme, trying to get people’s work/life balance back.

The programme started six years ago, and the average length of stay is one month, with prices from 8,000 Australian dollars ($6,100; £4,400) per week.

Most of the clients are Australian, but they also have some from Asia and Europe.

“We work on the guilt – I haven’t been a good parent, I haven’t been a good partner,” says Jane Enter, Retreat South’s clinical director.

“People should reconnect to who they are, it’s about getting a more balanced life.”

Back in Florida, JC – who first went to Workaholics Anonymous back in 2012 – now volunteers for the organisation.

“I have more time for fun and relationships with people,” she says. “I have the same job. However, because I have changed the way I think and act it is much more manageable.

“I place limits on the number of hours I work in a day.”