Sleep Deprivation as Cure for Depression

History of Approach

Nearly 30 years have passed since Anna Wirz-Justice, MD, first prescribed a night without sleep for a severely depressed 80-year-old woman. "She used to just sit around all day, feeling suicidal," says the Swiss neurobiologist. "She hardly spoke or moved.''

The remedy worked.  By the next morning, the elderly woman "was talking and moving around as if she were actually another person," Wirz-Justice says. "She told me that at about two or three in the morning, she felt like a black cloud had been lifted from her shoulders."

Was Wirz-Justice on to something? She and other researchers thought so -- at first. There is no denying that sleep deprivation temporarily eases depression. Up to 60% of depressed people will show a 30% improvement after just one night awake, according to a review article published in the January 1990 issue of the American Journal of Psychiatry. People who feel the most depressed in the morning and improve later in the day seem to benefit the most from a night without sleep.

But there was a problem: Patients tended to relapse into depression as soon as they did get a good night's sleep. Moreover, habitual sleep deprivation may be linked to long-term health problems such as high blood pressure and diabetes. The challenge then became to find a way of relieving depression by tinkering with sleep-wake cycles.

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Does it Work?

If a depressed mother stays up all night, or even the last half of the night, it is likely that by morning the depression will lift.  Although this sounds too good to be true, it has been well documented in over 1,700 patients in more than 75 published papers during the last 40 years. Sleep deprivation used as a treatment for depression is efficacious and robust: it works quickly, is relatively easy to administer, inexpensive, relatively safe and it also alleviates other types of clinical depression. Sleep deprivation can elevate your mood even if you are not depressed, and can induce euphoria. This throws a new light on insomnia.

This remarkable result is not well known outside a small circle of sleep researchers for three good reasons.  First, sleep deprivation is not as convenient as taking a pill.  Second, prolonged sleep deprivation is not exactly a desirable state; it leads to cognitive defects, such as reduced working memory and impaired decision making.  Finally, depression recurs after the patient, inevitably, succumbs to sleep, even for a short nap.  Nonetheless this is an incredibly important observation; it shows that depression can be rapidly reversed and suggests that something is happening in the sleeping brain to bring on episodes of depression.  All this offers hope that studying sleep deprivation may lead to new, unique and rapid treatments for depression.

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How does it Work?

Neuroscientists have been trying to solve this puzzle.  The first hint of what may be happening during sleep came from J. Christian Gillin, at the University of California at San Diego. Using imaging, he found that a small area of the cerebral cortex in the front of the brain  — the anterior cingulate cortex — which was consistently overactive in depressed patients, quieted to normal levels of activity after the patients were deprived of sleep. And when the patients were allowed to sleep, the activity in this area returned to the elevated levels.

Helen Mayberg at Emory University has shown that electrical stimulation of the anterior cingulate cortex, which disrupts normal activity, also reduces depression.  Some patients reported feeling immediate relief and calm after the procedure.

This tells us where in the cortex to look, but we also need to understand the changes that occur in the cortex during sleep. As you fall asleep, neurons in the brain stem that project throughout the cortex and keep it activated stop firing. The reduced stimulation from the brain stem disconnects the cortex from sensory input and there is a major shift in the pattern of electrical activity in the cortex. During the early part of the night the cortex is in a state of slow-wave sleep punctuated by brief periods of rapid-eye movement sleep (REM), which become more frequent and longer lasting toward early morning.

One major class of antidepressants, tricyclics, blocks REM sleep, which suggests that sleep deprivation may work against depression the same way. This is consistent with the tendency for depressed individuals to sleep longer than they do when they feel normal. Additional support for this hypothesis comes from genetic studies of families with short REM latency — the tendency to enter REM early in the sleep cycle. This condition disrupts slow wave sleep and extends REM sleep. The risk of depression is much greater if you come from a family with this genetic background. While this is a rare genetic defect that can only account for a small fraction of all depressed patients, these special cases give us valuable clues to conditions that predispose some people to clinical depression.

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Power of Hormones

Today, researchers are experimenting with ways to make use of the body's biological clock -- its circadian, or 24-hour, rhythms -- without asking patients to abandon rest altogether. The solution may lie in timing sleep to benefit from certain hormones that ebb and flow throughout the day.

For instance, thyroid stimulating hormone (TSH) helps control our metabolism and, indirectly, our levels of energy. An estimated 25% to 35% of depressed patients have low TSH levels. In recent years, researchers at the National Institute of Mental Health have found that sleep inhibits the release of TSH, while staying awake through the night and the early morning hours boosts it.

Some researchers are trying to manipulate the body's hormonal tides by having patients stay awake through the early morning hours for about a week. Doctors at the University Hospital of Freiburg in Germany tried this experiment on a group of depressed patients who felt better after one night without sleep: They told the patients to go to sleep at 5 p.m. that evening and rest until midnight the next night -- a total of 31 hours. Then the patients gradually eased back to a normal sleep cycle over the course of the week. One night they slept from 6 p.m. until 2 a.m., the following night from 7 p.m. until 3 a.m., until finally they returned to an 11 p.m. to 6 a.m. sleep cycle. Remarkably, the majority -- 75% -- didn't relapse into depression, according to results published last fall in the European Archives of Psychiatry and Clinical Neuroscience.

Methods

There are two methods of using sleep deprivation as a treatment for depression: total or partial deprivation.

Partial deprivation - sleeping the first half of the night only, and waking up halfway through - proved more effective than going to sleep later, or sleeping only the second half of the night. It is thought that partial sleep deprivation, sleeping up to 4 hours a night, will have the same antidepressant benefits as total sleep deprivation. Whereas with total sleep deprivation, the benefits are felt the following day, but are not long-lasting, sleeping four hours can be done continuously, over several days or even weeks, so naturally the benefits here are superior.

Even in patients with bipolar disorder can benefit. Research shows patients with bipolar disorder after sleep deprivation, are pulled from their depressed state to manic state. Manic states can cause sleep deprivation, lasting weeks and even months, so the cycle continues. The patient feels great, lighter in mood, and feel no need for sleep. Of course one should limit this, because of other health risks in prolonged sleep deprivation. Partial deprivation, up to 4 hours sleep is definitely the way to go for long-term treatment.

The ideal way to try for yourself, seems to be to stay awake a full night the first night, then limit yourself to 4 hours a night after that. Try this for a week or two, and see how you feel. I think in most cases, you will have positive results.

If you know someone suffering with severe depression, who barely has energy to talk to you, and no matter how you try to animate them, you have no success, try visiting them in the evening and keeping them awake all night. You will find the next morning their mood will be elevated, they will be more lucid and talkative, and more likely to want to move around and do things. Try then to convince them to use an alarm clock and wake themselves up after only four hours, they'll see for themselves how much better they feel.

The optimum time for sleep appears in some studies, to be from 10pm-2am, 11pm-3am, or12-4 am, underlining the fact that sleeping only the first half of the night provides the best results. In other reports, however, 2-6am 3-7am was optimal. It would depend presumably on your normal bedtime.

Sleep deprivation treatment was popular in the 1970s, but with the discovery of new and effective antidepressant medications, it was soon deemed old-fashioned and unhelpful. Nowadays doctors are reconsidering and endorsing this treatment, finding it helpful even alongside these medications, as the body seemed to accept medication more easily. Many psychiatrists were convinced by remarkable transformations of severely depressed, psychotic and even suicidal patients, back to relative normality after only a few hours. Antidepressant medication alongside sleep deprivation, has proven to help prevent relapse into the depressed state, although these studies are still ongoing.

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But Is It Practical?

Doctors admit that sleep deprivation regimen is tough to follow. Patients should probably try such sleep manipulation only under supervision and perhaps in a group to make the experience more enjoyable, says Edward DeMet, PhD, who studies sleep deprivation at the Veterans Affairs Medical Center in Long Beach. "Obviously, if you need to be driving the next day, you shouldn't do this," he says.

There are other ways to manipulate sleep to improve depressive symptoms. For instance, patients who go one night without sleep and who are exposed to bright light in the morning appear to prolong the emotional benefits of that sleepless night. People who try sleep deprivation while taking antidepressant medicine are also less likely to relapse, according to a study by Wirz-Justice and colleagues published in the August 1999 issue of the journal Biological Psychiatry.

Because antidepressants such as Prozac or lithium often take weeks to work, sleep deprivation may be most useful as a temporary tool that gives people a lift before the drugs take effect.

"It's much easier to pop a pill in the morning than stay up all night," says Wirz-Justice, a professor at the Psychiatric University Clinic's Chronobiology and Sleep Laboratory in Basel, Switzerland. "But sleep deprivation is very cheap and it's very fast. For patients who are severely depressed, the experience for that one day lets them know it's possible to get better. They finally have hope."


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