Why not sleeping for more than 24 hours can be a revolutionary treatment against bipolar depression

Why not sleeping for more than 24 hours can be a revolutionary treatment against bipolar depression


Keeping people awake in a hospital for hours may seem like a strange way to battle depression, but this is seen as a promising therapy for some people.

The first sign that something is happening is in Angelina’s hands .

While speaking in Italian with a nurse, he begins to gesticulate, forming circles in the air with his fingers. The minutes pass and Angelina becomes more animated . There is a musicality in his voice that he did not have a time before.

The lines on his forehead seem to soften. The way she purses her lips and the wrinkles around her eyes say a lot about her mental state .

Angelina is reviving at exactly the same time that the strength of my body seems to run out.

It is 2 in the morning and we are in a bright kitchen of a psychiatric guard in Milan , eating spaghetti. There is a lingering pain behind my eyes and I can not concentrate. Angelina, on the other hand, will not go to bed for another 17 hours.

Depriving someone from sleep has opposite effects on healthy people and those who suffer from depression. “

Francesco Benedetti, psychiatrist

I am preparing to face a long night. As if to reaffirm her conviction , Angelina removes her glasses, looks directly at me and points her gray eyes with her thumbs. ” Occhi aperti, ” he says. “Open eyes”.


It’s the second night that Angelina has been deliberately awake. For a person with bipolar disorder , who has spent the past two years mired in deep depression, this may sound like the last thing he would need. But Angelina – and the doctors who care for her – believe that this can be her salvation .

For two decades, Francesco Benedetti, who heads the Clinical Psychiatry and Psychobiology unit at San Rafael Hospital in Milan, has been investigating staying awake therapy , combined with exposure to bright light and lithium as a way to treat depression in those cases where the medication has not worked.

As a result, psychiatrists from the United States, the United Kingdom and several European countries are beginning to launch variants of that method in their own clinics.

These chronotherapies seem to work by setting in motion a slow biological clock and in doing so are shedding light on the pathology of depression and more generally on sleep function.

Silhouette of a woman sitting in a tunnelCopyright of the GETTY IMAGES image
Image caption This therapy began to be explored in the face of evidence that antidepressants had no effect in people with bipolar depression.

“Depriving someone from sleep has opposite effects on healthy people and those who suffer from depression,” says Benedetti. If one is to healthy and does not sleep one is cranky if you’re depressed, you can activate an immediate improvement of the mood of the person, as well as their cognitive skills .

Benedetti clarifies that there is a trap: when one goes to sleep and gets the day with the hours of sleep that he had lost, there is a 95% chance of having a relapse .

It was in 1959 when the antidepressant effect of sleep deprivation was first discussed It was in a report published in Germany. That attracted the attention of the German, Burkhard Pflug, who researched the subject in his doctoral thesis and in later studies in the 70s.

People go to sleep every two nights, but when they do they can sleep as long as they want “

Francesco Benedetti, psychiatrist

He said he had confirmed that keeping a person awake for one night could get them out of depression.

Alternative to medication

Benedetti became interested in that idea at the beginning of the 90s when he was a young psychiatrist.

Prozac had been released a few years earlier , revolutionizing treatments for depression, but that drug had not been tested in people with bipolar disorder. Anyway, Benedetti knew from experience that antidepressants had no effect on people with that disease .

His patients desperately needed an alternative and his supervisor, Enrico Smeraldi, had an ace up his sleeve. After reading some articles on sleep deprivation therapy, he tested those theories with his own patients and had positive results. “We saw that it worked,” recalls Benedetti.

“Patients with terrible histories, improved immediately . ” My task was to find a way to make them stay well. “

Image of the sun in the skyCopyright of the GETTY IMAGES image
Image caption Patients are kept awake under a bright light that simulates the sun’s rays.

The help of lithium

Benedetti and his colleagues began to dive into the scientific literature.

Several studies in the United States had suggested that lithium could prolong the effects of sleep deprivation . After investigation, they found that 65% of patients who took lithium three months later showed a sustained response to sleep deprivation.

Since even a brief nap can derail the efficiency of treatment , they also began to look for new ways to keep patients awake at night and took aviation-related medicine as a source of inspiration , where bright light is used to keep the pilots alert.

“We decided to use those three things and the effect was very good,” says Benedetti. By the end of the 1990s, they were routinely treating patients with triple chronotherapy: soil deprivation, lithium, and bright light.


Patients with bipolar depression

  • 70% of people with drug resistance responded to treatment with triple chronotherapy within the first week.
  • 55% showed a sustained improvement a week later.

Sleep deprivation could occur every two nights for a week and exposure to bright light for 30 minutes each morning could continue for two weeks. That protocol is still used today.

“We think not only of depriving people of sleep but also extending the period between sleeping and being awake from 24 to 48,” says Benedetti. ” People go to sleep every two nights, but when they do they can sleep as many hours as they want .”

Encouraging results

The San Rafael hospital began using the therapy in 1996. Since then, they have treated about 1,000 patients with bipolar depression , many of whom had not responded to drug treatments.

Man standing on a dock
Copyright of the GETTY IMAGES image
Image caption Unlike chronotherapy, antidepressants can take a month to produce an effect and in the interim may increase the risk of suicide.

The results speak for themselves: according to the most recent data, 70% of people with drug resistance for bipolar depression responded to treatment with triple chronotherapy within the first week and 55% had a sustained improvement a week later .

While antidepressants – if they work – can take a month to produce an effect and in the interim can increase the risk of suicide, chronotherapy produces an immediate and persistent reduction in suicidal thoughts , even after a single night of deprivation. of the dream.

Long-range depression

Angelina was diagnosed with bipolar disorder 30 years ago , when she was in her thirties. The diagnosis was followed by a period of intense stress : her husband was facing an on-the-job investigation and they were worried that they might lack money for themselves and their children.

When people are severely depressed, they do not have the usual response of an increase in melatonin at night and cortisol levels remain consistently high. “

Steinn Steingrimsson, psychiatrist

Angelina fell into a depression that lasted about three years . Since then, her mood has been oscillating, but she is depressed most of the time. She takes a battery of drugs -antidepressants, stabilizers, anxiolytics, and sleeping pills- that make her feel like a patient, a situation she does not like although she is aware of her problem.

If you had seen her three days before, it would have been difficult to recognize her. She had stopped wearing makeup, washing her hair and smelling bad. He felt quite pessimistic .

After his first night of sleep deprivation, he felt more energetic , which then diminished when he was able to go back to sleep. But despite that, she feels motivated by the presence of her hairdresser before my visit. I praise her appearance and she caresses her golden colored curls in gratitude for noticing it.

Simulated day

At 3 o’clock in the morning we moved to the room with lighting that simulates noon. Sunbeams enter through a skylight and fall on five armchairs lined up against the wall.

This is an illusion, of course. The blue sky is nothing but a colored plastic and the sun is a bright light, but the effect is stimulating . It is as if we were in a sunny room at noon, the only thing that is missing is the heat.

Silhouette of a woman holding her head
Copyright of the GETTY IMAGES image
Image caption These therapies can not only help improve the lives of many people, but also help health systems save money.

When I interviewed her seven hours earlier, interpreter by, Angelina’s face remained expressionless as she answered. At 3.20 she smiles and even tries to start a conversation in English, which she said to speak.

Towards the dawn, Angelina tells me of the story of her family that is beginning to write and invites me to stay with her in Sicily.

The function of sleep

How can it be that a simple thing like being awake produces such a transformation? Unraveling the mechanism is not simple: we still do not fully understand the nature of depression or the function of sleep . But recent studies have begun to provide some ideas.

The brain activity of people with depression seems different during sleep than when they are awake , compared to healthy people. During the day, there are signs that encourage us to stay awake and come from the circadian system, which is our 24-hour internal biological clock They were created to resist sleep.

These signals are replaced by those that promote sleep at night. The cells of our brain also work in cycles that are ostensibly excitable in response to stimuli when one is awake. In people with depression or bipolar disorder, those fluctuations seem more diffuse or absent.

Alarm clock
Copyright of the GETTY IMAGES image
Image caption The brain activity of people with depression seems different during sleep and when they are awake, compared to healthy people.

The internal clock

Depression is also associated with the alteration of the daily rhythm of hormonal secretion and the temperature of the body.

Like sleep signals, these rhythms are driven by the circadian system, which in turn is driven by a system of interacting proteins, encoded by the ‘gene clock’ that is expressed in the rhythmic pattern of each day . They handle hundreds of different cellular processes per day , giving each other time to turn on and off.

The circadian clock marks the pulse in every cell of the body, including the brain cells that are coordinated by an area of the brain called the suprachiasmatic nucleus, which responds to light.

“When people are severely depressed, their circadian rhythm tends to be flat, they do not have the usual response of an increase in melatonin at night and cortisol levels remain consistently high instead of falling at dusk and into the night,” says Steinn Steingrimsson, a psychiatrist at the University Hospital of Sahlgrenska in Gothenburg, who is testing a similar therapy.

Simple and cheap formula

Recovering from a depression is associated with the normalization of these cycles.

“I think that depression can be a consequence of a flattening of circadian rhythms and homeostasis in the brain,” says Benedetti. “When we deprive people of sleep, we re-establish that cyclic process.”

Routine, dream and light of day. It is a simple formula. If it can really reduce the incidence of depression and help people recover more quickly, it can not only help improve the lives of many people, but also help health systems save money.

A week after spending a night awake with Agelina, I called Bendetti to check his progress. She told me that after the third sleep deprivation, she experienced a complete remission of her symptoms and returned to Sicily with her husband. That week, they were about to celebrate 50 years of marriage.

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