Staying awake for more than 24 hours may be the fastest treatment for moderate to major depression.
Early research has shown six out of ten patients can get symptom relief within a day of this treatment, compared with the six to eight weeks it can take antidepressants to work.
Sleep deprivation is thought to work by boosting brain messengers such as serotonin - the same one that antidepressants act on.
Several studies have found 40 to 60 per cent of patients are helped by staying awake for a long time. One researcher described it as 'a remarkable transformation of often deeply depressed, psychotic, suicidal patients in a few hours into their pre-illness selves'.
However, the improvement is short-lived, disappearing after the patient slept.
Now researchers at the Medical University of South Carolina and Rhode Island Hospital are looking at providing longer relief by combining sleep deprivation with two other therapies. Pilot studies have shown that the effects of this treatment, known as triple chronotherapy, are rapid and are long-lasting - nine weeks in one trial.
The U.S. researchers will test the treatment in a larger study involving 80 patients with moderate to severe depression, postnatal depression or bipolar disorder.
Current treatments range from exercise and self-help groups to antidepressants. But medication doesn't work for everyone and some reports suggest it is no better than a placebo. It can also take two months for its effects to kick in.
The triple chronotherapy treatment, which is conducted over three days, combines sleep deprivation with 'bright light therapy' - where patients are exposed to a special lamp for up to an hour - and 'sleep-phase advancement' - when waking and sleeping times are changed.
The theory is that sleep deprivation has an anti-depressive effect; the bright light and sleep time changes then help reset the body clock, in turn helping the anti-depressive effect of sleep deprivation last longer. On day one, patients stay awake from 10.30pm, through the night and the whole of the next day. They then sleep from 6pm to 1am the following morning when the process is repeated, but sleeping and waking at different times.
Bright light therapy is given in the early morning of each of the three days - light is thought to stimulate the brain's hypothalamus, which controls mood, sleep and appetite, and to boost brain chemicals such as melatonin and serotonin.
On the second day, the patient sleeps from 8pm to 3am; on the last day, sleep starts at 10pm and finishes at 5am. From then on, patients continue with this 10pm to 5am sleep pattern.
Bright light and sleep time changes help reset the body clock, in turn helping anti-depressive effect last
A previous study at the University of California found significant improvements remained in 63 per cent of depressed patients seven weeks later.
New research at Tufts University has shed some light on what might be happening. It identified a protein called adenosine which is released when you're awake. Sleep deprivation increases levels of adenosine, which alters electrical signals in the brain, causing immediate improvement in mood.
'Triple chronotherapy typically reduces depressive symptoms within one to two days,' says psychiatrist Dr John Gottlieb, of Northwestern University Feinberg School of Medicine in Chicago and a leading expert in chronotherapy. 'It's as biologically active as antidepressants, inexpensive and has minimal side-effects.'
Carmine Pariante, professor of biological psychiatry at the Institute of Psychiatry, King's College London, adds: 'By putting sleep deprivation with other sleep-related therapies that have shown some effectiveness in depression, there is a reasonable expectation the antidepressant action will be stronger and more sustained.
'If this proves true, it will be an important step forward, both to understand mechanisms that cause depression and to find a new treatment for the one in four patients who don't improve with available treatments.'
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