Sleep, Insomnia and Nocturnal Panic Attacks
Sleep Drugs Found Only Mildly Effective, but Wildly PopularThe New York Times
October 23, 2007
By Stephanie Saul
Your dreams miss you. Or so says a television commercial for Rozerem, the sleeping pill. In the commercial, the dreams involve Abraham Lincoln, a beaver and a deep-sea diver. Not the stuff most dreams are made of. But if the unusual pitch makes you want to try Rozerem, consider that it costs about $3.50 a pill; gets you to sleep 7 to 16 minutes faster than a placebo, or fake pill; and increases total sleep time 11 to 19 minutes, according to an analysis last year. If those numbers send you out to buy another brand, consider this, as well: Sleeping pills in general do not greatly improve sleep for the average person.
American consumers spend $4.5 billion a year for sleep medications. Their popularity may lie in a mystery that confounds researchers. Many people who take them think they work far better than laboratory measurements show they do. An analysis of sleeping pill studies found that when people were monitored in the lab, newer drugs like Ambien, Lunesta and Sonata worked better than fake pills. But the results were not overwhelming, said the analysis, which was published this year and financed by the National Institutes of Health. The analysis said that viewed as a group, the pills reduced the average time to go to sleep 12.8 minutes compared with fake pills, and increased total sleep time 11.4 minutes.
The drug makers point to individual studies with better results. Subjects who took older drugs like Halcion and Restoril fell asleep 10 minutes faster and slept 32 minutes longer than the placebo group. Paradoxically, when subjects were asked how well they slept, they reported better results, 52 extra minutes of sleep with the older drugs and 32 minutes with the newer drugs. ''People seem to be getting a lot of relief from sleeping pills, but does getting 25 minutes of sleep really give you all that relief?'' asked Dr. Wallace B. Mendelson, the former director of a sleep disorders unit at the University of Chicago. ''A bigger aspect of this is that they change a person's perception of their state of consciousness.'' Dr. Mendelson is semiretired and is a consultant for pharmaceutical companies.
Dr. Karl Doghramji, a sleep expert at Thomas Jefferson University in Philadelphia, agreed. ''Sleeping pills do not increase sleep time dramatically, nor do they decrease wake time dramatically,'' he said. ''Despite those facts, we do find patients who, when they take them, have a high level of satisfaction.'' Dr. Doghramji has disclosed in the past that he is a consultant to pharmaceutical companies. Most sleeping pills work on the same brain receptors as drugs to treat anxiety. By reducing anxiety, the pills may make people worry less about not going to sleep. So they feel better.
Another theory about the discrepancy between measured sleep and perceived sleep involves a condition called anterograde amnesia. While under the influence of most sleep medications, people have trouble forming memories. When they wake up, they may simply forget they had trouble sleeping. ''If you forget how long you lay in bed tossing and turning, in some ways that's just as good as sleeping,'' said Dr. Gary S. Richardson, a sleep disorders specialist at Henry Ford Hospital in Detroit who is a consultant and speaker for pharmaceutical companies and has conducted industry-sponsored research. Sleep, after all, causes a natural state similar to amnesia, one reason toddlers often forget their violent nightmares by the next morning.
If you stay in bed, as most people taking sleeping pills do, amnesia is not a bad thing. Even some people who sleepwalked while taking Ambien, which was implicated in cases of odd, sometimes dangerous behavior while sleeping, believed they were having a good night's sleep. Rosemary Eckley, a graphic artist in New London, Wis., said she thought she was sleeping well on Ambien but woke to find her wrist broken, apparently in a fall while sleepwalking, she wrote in an e-mail exchange. Reports of sleep-eating and sleep-driving on Ambien are reminiscent of problems nearly 20 years ago with Halcion. Some people who took that drug to sleep on airplanes developed a condition known as traveler's amnesia. They landed at their destinations, then got lost or forgot where they were, prompting the authorities in several countries to withdraw Halcion from the market. Reports show that Ambien and similar drugs, advertised as safer than benzodiazepines like Halcion, can cause similar problems. The reports prompted the Food and Drug Administration to ask manufacturers to develop warning guides for distribution with virtually all sleep drugs.
Despite such problems, most specialists say sleeping pills are generally safe. Dr. Mark W. Mahowald, director of the Minnesota Regional Sleep Disorders Center, which is involved in documenting cases of sleep-eating under the influence of Ambien, said serious side effects were rare and should not discourage the use of the pills. The class of drugs known as nonbenzodiazepines, sometimes called ''Z'' drugs, includes Ambien, Lunesta and Sonata. Ambien and its generic equivalent, zolpidem, are the most widely used, together accounting for 40 percent of the market. Newer drugs like Lunesta and Ambien CR, a controlled-release formula, cost about $4 a pill. Zolpidem recently sold for $2 a pill on walgreens.com. Of the three drugs in the class, Sonata, which also retails for about $3.50 a pill, remains in the body the shortest time and, therefore, is normally used by people who have trouble falling asleep but no problem staying asleep.
The advocacy organization Public Citizen's Health Research Group says its benefits are so minimal it should not be used. King Pharmaceuticals, the maker of Sonata, did not respond to several messages seeking comment. A study by an Oregon State University group that reviews the safety and effectiveness of drugs found that Lunesta offered little benefit over generic Ambien or older benzodiazepines, but cost more. Jonae Barnes, a spokeswoman for Lunesta's maker, Sepracor, said the company strongly disagreed and added that the Oregon group did not adequately consider waking time after falling asleep, an area in which Lunesta performed better. Users also sometimes report that Lunesta leaves a bad taste in their mouths, according to studies of the drug. Dr. Mahowald said the older drugs, including Halcion, also known as triazolam, offered better value than the newer ones. ''We tend to use the old benzodiazepines,'' he said of his practice. ''They appear to be as effective as some of the newer ones, and they're infinitely less expensive.'' Dr. Mahowald said that his center participated in industry-sponsored clinical research, but that he did not personally work as a consultant or adviser to pharmaceutical companies. Such drugs, which include flurazepam, brand name Dalmane, and temazepam, Restoril, sell in generic versions for 30 to 50 cents each.
Another inexpensive alternative, and one of the most widely used sleep medications in this country, is the antidepressant trazodone. It works well in many patients, but some people say it leaves them groggy the next day, according to Dr. Daniel Carlat, a psychiatrist in Newburyport, Mass., who publishes The Carlat Psychiatry Report and declines industry financing. In men, trazodone has been linked to rare cases of priapism, prolonged and painful erections. Some patients who fear using sleeping pills turn to over-the-counter remedies like Tylenol PM and Advil PM. Those contain the painkillers acetaminophen and ibuprofen combined with an antihistamine, diphenhydramine, the ingredient in the allergy medication Benadryl. Antihistamines are known to make people sleepy, but there is little evidence that they improve sleep. They can also cause next-day sedation that impairs driving, as well as racing heartbeat and constipation.
The Medical Letter, which reviews drugs, recommends against using antihistamines for sleep. Some doctors say users of Tylenol PM may be taking acetaminophen they do not need. Acetaminophen overdoses can cause liver failure. Rozerem, with its unusual advertising campaign, has at least one benefit over other medications. Because it works by a different mechanism from the others, it is not a controlled substance and apparently does not affect the ability to form memories. It may be the sleeping pill of choice for elderly people who have trouble falling asleep, but suffer memory problems. Still, researchers and drug companies have yet to find a holy grail. ''The problem is, there is no ideal hypnotic,'' said Dr. Manisha Witmans, a sleep medicine specialist at the University of Alberta's Evidence-Based Practice Center. ''The magic pill for sleep has not been invented yet.''
Sleep Loss Linked To Psychiatric Disorders
ScienceDaily (Oct. 23, 2007) - It has long been assumed that sleep deprivation can play havoc with our emotions. This is notably apparent in soldiers in combat zones, medical residents and even new parents. Now there's a neurological basis for this theory, according to new research from the University of California, Berkeley, and Harvard Medical School. In the first neural investigation into what happens to the emotional brain without sleep, results from a brain imaging study suggest that while a good night's rest can regulate your mood and help you cope with the next day's emotional challenges, sleep deprivation does the opposite by excessively boosting the part of the brain most closely connected to depression, anxiety and other psychiatric disorders.
"It's almost as though, without sleep, the brain had reverted back to more primitive patterns of activity, in that it was unable to put emotional experiences into context and produce controlled, appropriate responses," said Matthew Walker, director of UC Berkeley's Sleep and Neuroimaging Laboratory and senior author of the study, which is to be published in the journal Current Biology. "Emotionally, you're not on a level playing field," Walker added. That's because the amygdala, the region of the brain that alerts the body to protect itself in times of danger, goes into overdrive on no sleep, according to the study. This consequently shuts down the prefrontal cortex, which commands logical reasoning, and thus prevents the release of chemicals needed to calm down the fight-or-flight reflex.
If, for example, the amygdala reacts strongly to a violent movie, the prefrontal cortex lets the brain know that the scene is make-believe and to settle down. But instead of connecting to the prefrontal cortex, the brain on no sleep connects to the locus coeruleus, the oldest part of the brain which releases noradrenalin to ward off imminent threats to survival, posing a volatile mix, according to the study. The study's findings lay the groundwork for further investigation into the relationship between sleep and psychiatric illnesses. Clinical evidence has shown that some form of sleep disruption is present in almost all psychiatric disorders. "This is the first set of experiments that demonstrate that even healthy people's brains mimic certain pathological psychiatric patterns when deprived of sleep," Walker said. "Before, it was difficult to separate out the effect of sleep versus the disease itself. Now we're closer to being able to look into whether the person has a psychiatric disease or a sleep disorder."
Using functioning Magnetic Resonance Imaging (fMRI), Walker and his team found that the amygdala, which is also a key to processing emotions, became hyperactive in response to negative visual stimuli - mutilated bodies, children with tumors and other gory images - in study participants who stayed awake for 35 hours straight. Conversely, brain scans of those who got a full night's sleep in their own beds showed normal activity in the amygdala. "The emotional centers of the brain were over 60 percent more reactive under conditions of sleep deprivation than in subjects who had obtained a normal night of sleep," Walker said. The team studied 26 healthy participants aged 18 to 30, breaking them into two groups of equal numbers of males and females. The sleep-deprived group stayed awake during day 1, night 1 and day 2, while the sleep-control group stayed awake both days and slept normally during the night. During the fMRI brain scanning, which was performed at the end of day 2, each was shown 100 images that ranged from neutral to very negative. Using this emotional gradient, the researchers were able to compare the increase in brain response to the increasingly negative pictures.
Since 1998, Walker, an assistant professor of psychology at UC Berkeley and a former sleep researcher at Harvard Medical School, has been studying sleep's impact on memory, learning and brain plasticity. During his research, he was struck with the consistency of how graduate students in his studies would turn from affable, rational beings into what he called "emotional JELL-O" after a night without sleep. He and his assistants searched for research that would explain the effect of sleep deprivation on the emotional brain and found none, although there is countless anecdotal evidence that lack of sleep causes emotional swings. "You can see it in the reaction of a military combatant soldier dealing with a civilian, a tired mother to a meddlesome toddler, the medical resident to a pushy patient. It's these everyday scenarios that tell us people don't get enough sleep." Walker said.
The body alternates between two different phases of sleep during the night: Rapid Eye Movement (REM), when body and brain activity promote dreams, and Non-Rapid Eye Movement (NREM), when the muscles and brain rest. "All signs point to sleep doing something for emotional regulation and emotional processing," Walker said. "My job now is to figure out what kind of sleep."
Reference: Yoo et al.: "The human emotional brain without sleep -- a prefrontal amygdale disconnect." Current Biology, Vol. 17, No. 20, R877-R878, Oct. 23, 2007.
Insomnia as Risk Factor for Anxiety Disorders?
Medscape Medical News, July 13, 2007 - A large prospective 11-year study in Norway found that chronic insomnia is a risk factor for developing anxiety but not for developing depression, although often anxiety and depression are present with insomnia. The study, led by Dag Neckelmann, MD, from Haukeland University Hospital, in Bergen, Norway, is published in the July issue of Sleep. The researchers write that insomnia is the subjective feeling of having difficulties initiating or maintaining sleep (DIMS) or having nonrestorative sleep.
They conclude that their results imply that "individuals reporting DIMS, in addition to receiving adequate treatment for their sleep disturbance, should be carefully examined for the presence of anxiety disorder as well as depression." A press release about this study issued by the American Academy of Sleep Medicine (AASM) notes that insomnia is the most commonly reported sleep disorder, and while about 30% of adults have insomnia symptoms, less than 10% of adults are likely to have chronic insomnia.
The investigators write that previous studies suggested that insomnia causes depression and/or anxiety disorders, but most studies were either cross-sectional or had a short follow-up of 1 to 2 years. They aimed to examine the relationship between insomnia and the development of anxiety disorders and depression in a population-based sample.
The team looked at data from 2 general health surveys of the adult population in the Nord-Trondelag county of Norway... The investigators conclude: "Focus on DIMS as a symptom of both anxiety and depression may facilitate the early detection of a mental disorder as well as the detection of comorbidity. Though not demonstrated, alleviating DIMS may reduce the risk of developing anxiety disorders."
Donna Arand, PhD, from the Sleep Disorders Center at Kettering Hospital, in Dayton, Ohio, and a spokesperson for the AASM, who was not involved in the study, told Medscape: "The long time period and large sample size makes this study notable. More important, this is the first study to clearly show that chronic insomnia is a risk factor for the development of anxiety disorders." She noted that, unlike previous studies, this study did not find that chronic insomnia is a risk factor for the development of depression, but it did replicate previous findings that chronic insomnia often coexists with anxiety disorders and depression. Dr. Arand added that the clinical implications of this study are that individuals with chronic insomnia will likely also have anxiety disorders and depression. Thus, they will need to be evaluated for these disorders and, if present, treated for them. "Since chronic insomnia often appears as the first problem, it needs to be recognized as a strong risk factor for anxiety, and consequently, chronic insomnia patients need to be followed long term and evaluated for these other conditions," she advised.
You're Getting Sleepy ... Or are you?
Anxiety and Stress Disorders Institute of