“You've got to be kidding me, Doc. I can barely keep my eyes open as it is, and you want me to pull an all-nighter?”

I smiled. “Yes, exactly that. Maybe even two or three.”

It started out benignly enough. Jodi (not the patient's real name) had been feeling more stressed between meeting the growing demands of her high-stakes job in business management and shouldering more chores while her husband was away on business trips. Strapped for time, she started neglecting her usual self-care routines—eating healthy, exercising, taking time to relax. Not surprisingly, her mood was poor.

Things soon grew worse. She no longer enjoyed activities that were usually the highlight of her day: story time with her children, chatting on the phone with her mom, reading a book. Although she was constantly exhausted, she could not get a good night's sleep; she would toss and turn and still feel tired even when she slept in. Her performance at work had also been suffering; she began missing days because she just couldn't get out of bed.

Jodi knows she should have recognized these warning signs sooner. She had experienced major depression twice before, once in college and again in her late 20s after a breakup. Now in her late 30s, she had been off antidepressants for years. Yet she found herself back in that dark place, barely eating and unable to concentrate enough to read even a short paragraph. Her thoughts circled around the same unpleasant memories and nagging fears. She felt hopeless and guilty.

When she came to see me, I confirmed what Jodi already suspected: she had relapsed into a major depressive episode. Thankfully, she was not having thoughts of hurting herself, and because she had good support from her family and friends, she would not need to be hospitalized. I recommended that she start on an antidepressant immediately. Jodi agreed but was disappointed to learn it might be anywhere from four to six weeks before her medication took effect. She had already fallen behind on work, the holidays were coming up, and she did not want to put her life on hold for this depression any longer. “Isn't there something that will work faster?” she lamented.

“Well, there is one strategy we could try,” I said. “How do you feel about skipping a few nights of sleep?”

Jodi's jaw dropped. “You've got to be kidding me, Doc. I can barely keep my eyes open as it is, and you want me to pull an all-nighter?”

I smiled. “Yes, exactly that. Maybe even two or three.”

Standard antidepressant therapies are often effective in treating depression, but it takes time for them to work. In recent years research has focused on trying to find treatments that could improve symptoms within days as opposed to weeks. Although it seems counterintuitive, an old and often forgotten approach to improving mood rapidly involves short-term sleep deprivation. As a 2015 review in Current Psychiatry Reports noted, therapies that manipulate sleep can significantly improve depressive symptoms. The treatment is not for everyone—elderly patients and those with cognitive impairment, for instance, would not be good candidates—nor should people try it without a clinician's guidance. Still, it can help bring relief before medication kicks in.

Sleep issues are a core symptom of depression. They exacerbate fatigue and cognitive deficits, which are also core symptoms, making daily functioning even more challenging. People often cope by taking daytime naps, which makes falling asleep at night difficult, feeding the cycle of sleep dysregulation. These observations have led many researchers to ask what the connection between sleep and mood is and what biological determinants underlie this relation.

Credit: KAROLIS STRAUTNIEKAS

All creatures sleep—or at least exhibit a circadian rhythm based on the earth's light-dark cycle. In animals, populations of nerve cells have rhythmic activity thought to be the basis of an internally generated timekeeper. This master clock can be found in the brain's suprachiasmatic nucleus. If this area is damaged, daily bodily rhythms become erratic. Research has also shown that genetic regulation of circadian rhythms is off-kilter in people with major depression.

Circadian-sensitive circuits are influenced by external cues, the most important being sunlight. They receive information about the timing and duration of sunlight from the eye: a special subset of cells in the retina, found at the back of the eyeball, transmits this information, even in people who are blind.

Many of us have experienced the power of circadian misalignment when traveling to another time zone. The mismatch between the environmental light-dark cycle and that of our neural circadian pacemakers is more commonly referred to as jet lag. (We undergo this experience to a lesser degree twice a year during daylight saving time switches.) It can take several days for neural circuits to become entrained to the new light-dark schedule, but in the interim, sleep is disrupted, appetite does not match up with mealtimes and our state of mind can suffer.

But could adjusting these cycles reset our mood and, in turn, address mood disorders? In fact, it has been known for 200 years that sleep deprivation can treat depression rapidly. (In 1818 German psychiatrist Johann Christian August Heinroth described the therapy in his Textbook of Disturbances of Mental Life.) Since the 1960s numerous clinical studies have shown that as little as one night of sleep deprivation can relieve symptoms, and a 2015 paper reported swift improvement in 50 to 80 percent of subjects.

Sleep is generally thought to be a mood-stabilizing force. It is certainly one of the first symptoms targeted by clinicians, usually with medications, to help patients feel better. Furthermore, studies have shown that sleep deprivation has an effect on neurotransmitter activity throughout the brain, just like some medications. In 2015 scientists at the University Medical Center Freiburg in Germany, the University of Bonn in Germany, the University of Naples Federico II in Italy and the National Institutes of Health discovered that the effects of sleep deprivation, tricyclic antidepressants and ketamine on mood may all rely on the same molecular target, a receptor in the brain's frontal lobes whose activity may ultimately influence brain connectivity related to mood regulation.

Unfortunately, the gains made by sleep-deprivation therapy alone are not long-lasting. Typically depressive symptoms return within one week, which still leaves four to six weeks before antidepressants can kick in.

There may, however, be a way to maintain this therapy's benefits using the ultimate circadian rhythm calibrator: sunlight. In one of the earliest studies combining sleep and full-spectrum light therapies, psychiatrists at the University of Vienna asked 20 patients with depressive symptoms who had undergone sleep deprivation to take an antidepressant medication in conjunction with either dim or bright light exposure. Their findings, published in 1996, showed that among those patients who responded well to sleep deprivation, receiving daily bright light maintained the antidepressant effect of that limited sleep during a trial period of seven days.

My colleagues and I are now investigating whether this benefit can be maintained even longer. Thus, I offered Jodi the opportunity to participate in a new study of “wake therapy,” which combines sleep deprivation, timed sleep (that is, following a schedule in which sleep time shifts over a number of days) and light therapy. She was hesitant—but then again, she was already sleeping poorly, so what did she have to lose?

To avoid workplace fatigue, Jodi started the treatment that weekend. Adhering to a schedule we had tailored for her, she went through a period of prolonged wakefulness, an “all-nighter.” After that point, she followed a prescribed routine of specific bed and wake times to shift her sleeping cycle. She also sat in front of a full-spectrum light box at breakfast every morning.

When I saw Jodi the next week, she reported that although staying up had been tough, she had noticed a significant improvement in her symptoms. She no longer felt depressed, was able to go back to work and was handling the stresses of everyday life more successfully. We continued to work together, and within a few weeks, with the help of medications, wake therapy and psychotherapy, Jodi was herself again—just in time for the holidays.