Off-Label Prescribing for Insomnia: What to Expect

Several drugs approved for insomnia are in the doghouse these days, and physicians are doing a fair amount of off-label prescribing. What medications should we expect to be prescribed in lieu of zolpidem (Ambien) and temazepam (Restoril)?

Using a “translational approach,” McGill University researchers have reviewed a host of medications with sedative properties and found the evidence base for some is stronger than for others. Here are the drugs they’ve found are most likely to work.

Insomnia treated with sleeping pill substituteSeveral drugs approved for insomnia are in the doghouse these days, and physicians are doing a fair amount of off-label prescribing. What medications should we expect to be prescribed in lieu of zolpidem (Ambien) and temazepam (Restoril)?

Using a “translational approach,” McGill University researchers have reviewed a host of medications with sedative properties and found the evidence base for some is stronger than for others. Here are the drugs they’ve found are most likely to work.

Why Not Stick With the Tried and True?

Z-drugs such as zolpidem and benzodiazepines such as temazepam may be fine for short-term or occasional use. But lots of people who take these sleeping pills go on to become chronic users.

This can cause problems. People who take a Z-drug or a benzodiazepine nightly for months and years often experience adverse effects: a decrease in deep (or slow-wave) sleep and/or cognitive and motor impairments the next day. Some develop drug dependency.

The Off-Label Prescribing Dilemma

So where’s the next generation of sleeping pills in line to replace the ones we’re using now? A few new drugs are in the pipeline, but none I’m aware of are going up for FDA approval soon. As often happens, we’ve got to fall back on drugs already approved to treat other health problems. It’s perfectly legal for doctors to prescribe such drugs off label as treatment for insomnia.

The problem lies in knowing which other drug(s) to choose. Medications approved for insomnia have demonstrated their efficacy in at least two randomized clinical trials (RCTs) conducted on people with insomnia (and no other related condition). Compared with placebo, they’ve been found to significantly improve sleep. Medications approved for other health conditions—such as depression, anxiety, or neuropathic pain—may have known sedative properties. But in many cases they haven’t been tested for efficacy on people with simple insomnia.

A Translational Approach

In an in-depth review paper published this month in Pharmacological Reviews, the McGill University researchers propose instead using a translational approach to evaluate these drugs for efficacy in treating insomnia. This involves integrating what basic scientific research has shown about a drug’s pharmacology and mechanism of action with clinical data and current medical practice.

Using this approach, the researchers went on to identify medications most likely to serve as effective alternatives for Z-drugs and benzodiazepines. Here they are:

Drugs That Act on the Melatonin System

1. Prolonged-release melatonin (PRM): FDA-approved dietary supplement sold over the counter in the United States; sold as a prescription drug (2 mg/day) in Europe. “Good evidence,” based on 4 RCTs, that PRM is effective for insomnia disorder in adults over age 55 (particularly in reducing time to sleep onset). There’s no evidence that PRM is effective for younger adults with insomnia. (Caveat: The quality control of dietary supplements sold in the United States is not nearly as reliable as the control of prescription medications. Your physician may be able to steer you toward a reliable brand.)

2. Ramelteon (Rozerem): FDA-approved drug for treatment of sleep onset insomnia. “Strong evidence,” based on 2 meta-analyses, that the drug reduces subjective time it takes to fall asleep but no evidence that it helps people sleep longer.

3. Agomelatine (Melitor): Not available in the United States but approved for treatment of major depressive disorder in Canada and Europe. “Good evidence,” based on 1 review and 2 RCTs, that this drug reduces sleep latency in people with depression. Unlikely to improve sleep in people with simple insomnia.

A Drug That Acts on the Orexin System

4. Suvorexant (Belsomra): FDA-approved drug for treatment of insomnia disorder. “Strong evidence,” based on 2 systematic reviews, that the drug reduces insomnia symptoms at doses of 15 mg and higher. It purportedly increases total subjective sleep time and decreases subjective time to sleep onset. (Caveat: Because this drug is a relative newcomer, less is known about its real-world effectiveness and actual side effects. For more information, read my earlier post about Belsomra and take a look at the reader comments.)

Sedating Antidepressants

5. Low-dose doxepin (Silenor): FDA-approved drug for treatment of sleep maintenance insomnia that acts on the histamine system. “Strong evidence,” based on 1 systematic review, that this drug enhances sleep maintenance by reducing nighttime wake-ups. It has not been found to cut down on time to sleep onset.

6. Trazodone: FDA-approved drug for treatment of depression. At low doses, commonly prescribed off label for treatment of insomnia. It acts on the histamine, serotonin, and catecholamine systems. “Good evidence,” based on 2 RCTs, that trazodone reduces insomnia symptoms in people who are taking selective serotonin reuptake inhibitors (SSRIs) to manage depression. This is the only conclusion drawn by the McGill researchers about trazodone. It does not account for the drug’s great popularity with physician prescribers, who for decades have been prescribing trazodone for insomnia rather than Z-drugs and benzodiazepines.

More on Trazodone

So I looked at another paper, this one a systematic review of trazodone for insomnia published in Innovations in Clinical Neuroscience in August 2017. From a pool of 45 studies (the inclusion criteria were evidently less stringent for these researchers than for the McGill researchers, who reviewed 16 studies of trazodone), the second team of researchers concluded that trazodone “is a generally safe therapeutic that has been repeatedly validated as an efficacious treatment for insomnia, particularly for patients with comorbid depression,” with some evidence that it decreases sleep latency, increases sleep duration, and improves sleep quality. Side effects, which may show up in people taking doses higher than 100 mg, include daytime sleepiness, headache, and hypotension, increasing the risk of falls.

The evidence base for trazodone’s effectiveness as a drug for people with simple insomnia is sparse yet suggestive of similar benefits, the second research team reports. (Results of a recent 6-week clinical trial comparing 3 active insomnia treatments—behavioral therapy, zolpidem, and trazodone—are not yet available. Stay tuned.)

An Anticonvulsant Drug

7. Pregabalin: FDA-approved drug for treatment of neuropathic pain, seizures, and fibromyalgia. There is “good evidence,” based on 2 review papers, that pregabalin is effective in reducing symptoms of insomnia in generalized anxiety disorder. There is also “good evidence,” based on 1 review, that the drug is effective in reducing symptoms of insomnia in fibromyalgia. But no evidence base for pregabalin as a treatment for simple insomnia exists.

The medical treatment of insomnia has always been problematic, even more so in the past than today. While your physician may be reluctant to keep writing prescriptions for zolpidem, other, possibly safer medications may be available when behavioral treatments for insomnia don’t suffice.

Was My Insomnia Due to Lack of Light?

A daily routine and daily exposure to sunlight help regulate sleep. Research backs this up and I see it in myself. My best sleeps come after days when I get up and out and do the things I do at the usual time.

Last night my sleep went off the rails, and I’m convinced the problem was at least partly related to light. Let me explain.

Insomnia can develop with too little exposure to daylightA daily routine and daily exposure to sunlight help regulate sleep. Research backs this up and I see it in myself. My best sleeps come after days when I get up and out and do the things I do at the usual time.

Last night my sleep went off the rails, and I’m convinced the problem was at least partly related to light. Let me explain.

An Unusual Tiredness

My husband and I were viewing old slides last night, and around 9 p.m. I complained about how tired I was.

“Why?” he asked. Normally at 9 p.m. my evening has barely begun.

I couldn’t explain it. I’d gotten up at the regular time, had coffee, eaten regular meals. Worked in the morning, exercised late in the afternoon. Had a glass of wine before dinner and a decent night’s sleep the night before. Nothing that came to mind could explain how really bone tired I felt.

Staving Off Sleep

Even so, I didn’t go to bed right away. If I’ve learned anything about sleep, it’s that going to bed early can start people like me on a path to perdition. It can lead to:

  • Sleep onset insomnia, or trouble falling asleep at the beginning of the night
  • Sleep maintenance insomnia, or broken sleep with awakenings every hour or two
  • Early awakening insomnia, or waking up in the twos, threes, or fours and being unable to fall back to sleep

So tired though I was, I headed for my favorite easy chair, where I typically read for a couple hours until I’m sleepy enough to fall asleep. Then at some point I went to bed.

A Short Night—Or Was It?

The next thing I knew I woke up in the dark and it felt like morning. I hurried to turn off the alarm clock because my husband was going to sleep in. But when I looked at the time (my clock stays dark at night except when I press the button on top) I saw it wasn’t even close to 5:30, my normal wake-up time. It was only 2:15.

So I went back to bed. At the next awakening, I asked my husband what time it was and he whispered it was almost 5:30. I turned off the alarm.

Only it wasn’t 5:30, and I didn’t turn off the alarm, I later learned from my husband. That whispered exchange must have been a dream. Because when I went downstairs and turned on a light, the clock on the stove said 4 a.m.

What the heck?!

I’d thought my early awakening insomnia was a thing of the past. It was so far from normal now that I was determined to parse it out.

Reconstructing My Day

Two clues lay beside the easy chair where I sat down to read last night.

  • My book: It was open two pages beyond the bookmark, where I’d stopped reading the night before. Guess I didn’t read for very long!
  • Medicine I take every night to help with digestion: Two capsules lay on the desk beside the chair together with a full glass of water, untouched.

Obviously I’d fallen asleep in my chair way earlier than usual. But what had knocked me out so quickly and completely that I forgot to take my medicine? Read just two pages when normally I’d read for at least two hours?

Was Lack of Light the Culprit?

Suddenly it came to me. I had done something out of the ordinary in the middle of the afternoon. I went to a concert, where for two hours I sat under low light listening to Haydn string quartets.

That wasn’t all: the first violinist was super-animated as he played and kept swinging his feet up into the air. Every time those feet came off the ground I thought of a plane taking off, and that image juxtaposed onto the Haydn was jarring. I decided to close my eyes—and kept them closed for the rest of the concert.

So for two hours in the afternoon, at a time when my brain would normally be exposed to light, I sat in near-total darkness. That, added to our half-hour session viewing slides in a dark living room, might have affected my body clock, causing sleepiness to occur earlier than usual and early morning wake-ups.

Bright Light Exposure: Rules to Live By

As ubiquitous as it is, light might not seem like it would have much impact on sleep. But it does. People contending with circadian rhythm disorders have to pay special attention to light, and light or a lack thereof may figure in insomnia, too. Keep these things in mind:

  • Lack of sufficient light exposure during the daytime tends to have a negative effect on sleep duration and sleep quality. Get exposure to sunlight every day by spending time outside or inside near a window.
  • Exposure to bright light early in the morning will help you fall asleep earlier.
  • Exposure to bright light in the evening tends to delay the onset of sleep.

 

Coffee: The Sleepless, Too, Can Enjoy the Benefits

I love coffee and I’m always glad to hear coffee is beneficial to my health. Two new studies—one of humans and the other of mice—add to this growing body of knowledge.

Yet coffee contains caffeine, and people with insomnia are often advised to cut down on caffeine because it interferes with sleep. Is there a middle course the sleepless can steer to avoid the harms and reap the benefits?

Coffee | insomnia sufferers can enjoy health benefits & avoid the harmsI love coffee and I’m always glad to hear coffee is beneficial to my health. Two new studies—one of humans and the other of mice—add to this growing body of knowledge.

Yet coffee contains caffeine, and people with insomnia are often advised to cut down on caffeine because it interferes with sleep. Is there a middle course the sleepless can steer to avoid the harms and reap the benefits?

Decaf is always an option. Caffeinated coffee may be OK, too—if you’re willing to experiment. Here’s more on that following a brief look at the new findings:

Coffee Reduces Mortality

The latest study of coffee and mortality found that coffee drinkers live longer than non-coffee drinkers. In this large, multi-ethnic study, people who drank one cup a day were 12% less likely to die than non-coffee drinkers. The odds were even better for people who drank two or three cups a day: they were 18% less likely to die.

The particular chemical or compound in coffee that protects against heart disease, cancer, respiratory disease, stroke, diabetes, and kidney disease is still unknown. But it probably isn’t the caffeine. Coffee’s life-protecting benefits were significant for people who drank caffeinated coffee and for those who drank decaf. They were significant for smokers and non-smokers; African-Americans, Asians, Latinos, and whites; and people of all ages.

Caffeine Reduces Pain Sensitivity

Pain can interfere with sleep. But a growing body of literature suggests that lack of sleep or poor quality sleep increases our sensitivity to pain, and that insomnia exacerbates existing pain and predicts new-onset pain.

In a new study, Boston researchers found that sleep deprivation in healthy mice increased their pain sensitivity. The greater the sleep deprivation, the more exaggerated were their responses to pain. After a period of normal sleep, their reaction to pain was much less pronounced.

Then, while still in a state of sleep deprivation, the mice were given caffeine or modafinil (a drug that promotes alertness). Their pain tolerance increased, similar to what they experienced after a full period of normal sleep. So if you’re experiencing pain and trouble sleeping, a caffeinated beverage like coffee may reduce your pain more effectively than drugs prescribed for pain relief.

Reaping the Benefits, Avoiding the Harms

It looks like moderate coffee drinking is associated with better health and resilience to pain. But if you’re prone to insomnia, you’ll need to do a bit of experimenting to find out when and how much you can drink without harming your sleep.

Here are some facts to be aware of as you’re figuring it out:

  • The effects of caffeine vary greatly from one person to the next. This is largely attributable to genetic factors. Drinking coffee later in the day may keep you wakeful and degrade the quality of your sleep, or it may not affect your sleep at all.
  • Research has shown that early risers tend to be the most sensitive to caffeine. People who go to bed and wake up somewhat later have less caffeine sensitivity, and the sleep of night owls may not be affected by caffeine at all.
  • People metabolize caffeine at widely varying rates. The average half life of caffeine (the point at which the amount of caffeine in the blood has decreased by half) is 5 to 6 hours. But the half life of caffeine can vary from 2 to 12 hours. Smokers typically metabolize caffeine quickly; pregnant women, slowly. And we all metabolize caffeine more slowly as we age.

Timing Is Important, Too

When you can safely drink your last cup of coffee may depend in part on the insomnia symptoms you have. For example, I have sleep onset insomnia, or trouble falling asleep at the beginning of the night. I find that drinking coffee after 2 p.m. can keep me wakeful so I avoid coffee later in the day.

But Lesley, who comments on my posts from time to time, has trouble with sleep maintenance insomnia, falling asleep easily at the beginning of the night but waking up in the middle of the night. After successfully working to consolidate her sleep with sleep restriction, she worked out for herself a different coffee drinking routine:

I know I’m pretty caffeine sensitive and for a long time drank only decaffeinated drinks. . . . After reading recent research . . . on caffeine’s effects on sleep and the body clock, I’ve now added caffeine back into my daily routine. I have sleep maintenance insomnia plus an early to bed/early to rise body clock, and I commonly struggle to stay awake in the evenings, and even the late afternoon.

But with much experimentation I’ve found that one instant coffee in the late afternoon and another about 2.5 hours before bedtime helps massively, without affecting me getting to sleep. Of course we’re all different in our tolerance to caffeine, and it’s very much trial and error. But it’s an extremely useful tool to be aware of.

Lesley puts it well: with a bit of trial and error experimentation, we insomniacs may be able to have our coffee and drink it, too.

If you’re a coffee drinker, how does it affect your sleep?

Restless REM Sleep May Lead to Hyperarousal

Do you tend to dwell on upsetting thoughts? Does your arousal thermostat feel like it’s set too high, making it hard for your body to relax and fall or stay asleep? Insomnia is often described as a disorder of hyperarousal, yet how and why the hyperarousal develops is unclear.

Now a team of 13 sleep scientists from three countries have taken findings from different lines of research, conducted a study of their own, and come up with a plausible explanation for why our minds and bodies feel like they’re stuck in overdrive and just can’t stop. Here’s what may lie behind our trouble falling and staying asleep.

insomnia, characterized by fragmented REM sleep, leads to slow emotional processingDo you tend to dwell on upsetting thoughts? Does your arousal thermostat feel like it’s set too high, making it hard for your body to relax and fall or stay asleep? Insomnia is often described as a disorder of hyperarousal, yet how and why the hyperarousal develops is unclear.

Now 13 sleep scientists from three countries have taken findings from different lines of research, conducted a study of their own, and come up with a plausible explanation for why our minds and bodies feel like they’re stuck in overdrive and just can’t stop. Here’s what may lie behind our trouble falling and staying asleep.

Two Kinds of Sleep

Whether we sleep poorly or well, our nights are composed of two kinds of sleep: REM sleep, when most dreaming occurs and when the eyes move rapidly from side to side; and non-REM, or quiet, sleep. The deepest stage of non-REM sleep is called slow-wave sleep.

In the past, scientists thought that insomnia probably had to do with a dysfunction related to slow-wave sleep or some other feature of non-REM sleep. This may be the case for some people with insomnia.

But the results of two recent studies suggest that the problem may lie elsewhere. The findings show that sleep maintenance insomnia (the type of insomnia involving middle-of-the-night awakenings) is characterized by fragmented REM sleep.

Importance of REM Sleep

There’s solid evidence now that REM sleep—most of which occurs in the second half of the night—helps us process negative emotions such as fear and anger and self-conscious emotions such as guilt, embarrassment, humiliation, and shame. In studies where participants are forced to rise too early, they often wake up in a bad mood.

The reason is that they’ve gotten insufficient REM sleep, say sleep scientists, and the full processing of emotion has not had a chance to occur. As a result, any negative emotion they experienced the previous day may still retain its emotional charge.

There’s also preliminary evidence that fragmented REM sleep (such as that found in insomnia) hinders the overnight resolution of emotional distress.

Authors of the current study, published in Proceedings of the National Academy of Sciences, wanted to take this research further. They predicted that fragmented (or restless) REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to the accumulation of arousal, and eventually hyperarousal, associated with insomnia.

A Two-Part Study

First, the researchers tested 32 people—16 with insomnia disorder and 16 normal sleepers—in a sleep lab for two nights. The object was to find out if restless REM sleep correlated with the frequency of participants experiencing thought-like rather than dream-like mental activity at night (as assessed by questionnaires). Thought-like nocturnal mentation—when we’re mentally chewing on a problem, for example—is specifically associated with restless REM sleep.

In addition, the researchers looked for relationships between restless REM sleep, duration of emotional distress, and chronic hyperarousal in data compiled on 1,199 people participating in the Netherlands Sleep Registry. The NSR is a psychometric database created to facilitate research on factors that discriminate people with insomnia from people without sleep complaints.

Restless REM Sleep, Emotional Distress, Hyperarousal

The investigators used sophisticated statistical methods to analyze their data, and here’s what they found:

  • Compared with normal sleepers, insomniacs were slower to recover from long-lasting emotional distress. The more severe the insomnia, the slower the recovery.
  • Thought-like mental activity was more frequent among insomniacs than normal sleepers, and it was significantly associated with emotional distress lasting overnight (but not with short-lasting distress resolved during the previous day).
  • The more severe the insomnia, the more people reported symptoms of hyperarousal.
  • Long-lasting emotional distress accounted for 62.4% of the association between hyperarousal and the thought-like mental activity occurring during restless REM sleep.

What It Means for Us

The findings conformed to researchers’ expectations. So here’s their explanation for why insomniacs, both mentally and physiologically, keep going and going and can’t seem to relax into sound, consolidated sleep: mental activity we experience at night—which is associated with fragmented REM sleep (and increased eye movement density)—interferes with the overnight resolution of emotional distress. So we awaken with the distress still in place, which ramps up arousal. Over time, this could lead to a state of chronic hyperarousal.

It sounds plausible to me. Your thoughts?

Insomnia: Too Much Alpha Wave Activity at Night

The brains of people with insomnia are active at night, even during quiet sleep. This activity isn’t often noted in sleep studies, where the point is to identify dominant wave forms. But looking closer, scientists are discovering slight but crucial differences in insomniacs’ brain waves at night, which may explain our trouble falling and staying asleep.

“Alpha wave intrusion” is a term used to describe the wake-like brain activity observed during the deep sleep of people with fibromyalgia and major depression. Now a new study in the Journal of Sleep Research presents evidence of abnormal alpha wave activity in insomniacs’ brains at night. Here are the two main findings:

Insomnia is characterized by greater alpha wave activity at nightPicture the brain at night. It’s mostly quiet except during rapid eye movement (REM) sleep. Then clusters of neurons in the brain stem start firing away like mad. These bursts of activity are perfectly normal during REM sleep, alternating with periods of quiet non-REM sleep through most of the night.

The brains of people with insomnia are more active at night—even during non-REM sleep. This activity isn’t often noted in sleep studies, where the point is to identify dominant wave forms. But looking closer, scientists are discovering slight but crucial differences in insomniacs’ brain waves at night, which may explain our trouble falling and staying asleep.

Alpha wave intrusion is a term used to describe the wake-like brain activity observed during the deep sleep of people with fibromyalgia and major depression. Now a new study in the Journal of Sleep Research presents evidence of abnormal alpha wave activity in insomniacs’ brains at night. Here are the two main findings:

Trouble Falling Asleep

The descent from wakefulness into deep sleep occurs fairly quickly in healthy sleepers. The pressure to pay off the day’s sleep debt is strong, compelling a rapid descent into deep (slow-wave) sleep.

But in people with sleep onset insomnia, who typically take more than 30 minutes to fall asleep at night, the descent takes quite a bit longer, research shows. Insomniacs—for unknown reasons—seem to have reduced sleep pressure. Not only does it take us longer to fall asleep. It also takes us longer to descend into deep sleep, the really restorative stuff.

Why the Slow Descent?

The research team investigating alpha wave activity looked at the sleep studies of 18 good sleepers and 10 insomniacs and found one difference that occurred before sleep began. Alpha waves—associated with a relaxed, meditative state of consciousness that occurs when the eyes are closed—are predominant in the period leading up to sleep. They’re generated by neurons firing at frequencies of 7.5 to 12.5 cycles per second.

As the healthy sleepers in the study were falling asleep, the alpha rhythms in their brains began to fluctuate and decay. But the alpha wave activity in insomniacs’ brains continued going strong.

Sleep onset insomnia may have something to do with decreased alpha variability, the researchers concluded. Insomniacs are relaxed and ready for sleep—yet (again for unknown reasons) we remain stuck in alpha mode.

Waking Up at Night

Alpha waves may also play a role in sleep maintenance insomnia. Polysomnogram studies show that normal sleepers awaken at least a few times a night but are mostly unaware of these awakenings.

People with sleep maintenance insomnia, in contrast, are conscious of waking up at night. These awakenings make our sleep feel fitful and less restorative. (And some sleep maintenance insomniacs are told their problem involves alpha wave intrusion following a sleep study.)

Adults spend up to 80% of the night in non-REM sleep, and in the alpha wave study, different kinds of alpha activity occurred in the brains of healthy sleepers and insomniacs throughout non-REM sleep. Brief arousals in the healthy sleepers were characterized by alpha waves that stayed well below the frequency of alpha waves during conscious wakefulness.

But the alpha frequencies in participants with insomnia rebounded to wake levels. In this situation, a sleeper might be easily awakened by noise or movement and memories could be formed. It might account for why so many insomniacs complain of light and/or broken sleep.

The Take-Away

Higher alpha frequencies during brief arousals and lower alpha variability at the approach of sleep fit with the hyperarousal theory of insomnia, which suggests that people prone to insomnia experience higher levels of arousal around the clock. As for how to correct these alpha abnormalities, we’ll have to wait and see.

Cut Down on Nighttime Wake-Ups: A Survey & Advice

Who would you guess wakes up more frequently at night because of stress and anxiety? Adults who are young, middle aged, or old?

What the Sleepless Nights survey tells us about middle-of-the-night awakeners, together with a dash of commentary and advice.

Sleep is less deep & restorative when disrupted by wake-ups in the middle of the nightWho would you guess wakes up more frequently at night because of stress and anxiety? Adults aged

(a) 18 to 24

(b) 25 to 34

(c) 35 to 44

(d) 45 to 54

(e) 55 and above

According to a recent survey of 1,000 adults in the United States, the youngest adults lead the pack, with 46% of the 18- to 24-year-olds reporting stress-related wake-ups at night.

Does this surprise you? Maybe so and maybe not. But data can sometimes contradict expectations. Following are a few more findings taken from the Sleepless Nights survey conducted October 19 by OnePoll,* an online market research firm, together with a dash of commentary and advice.

Waking Up in the Middle of the Night

It’s not unusual to wake up once or even a few times during the night. In fact, in the OnePoll survey, less than 1% of the respondents reported never waking up at night. But having lots of nighttime awakenings is a problem. It’s a symptom of sleep maintenance insomnia.

You might think the total amount of sleep you get is actually more important than the number of wake-ups you experience. But this isn’t true. Sleep interrupted by frequent wake-ups is not as restorative as the same amount of sleep gotten all at one time, according to a study published in the November issue of Sleep. People who sleep in fits and starts miss out on a significant amount of deep sleep, the study shows. They report feeling unrefreshed in the morning, and waking up in a bad mood.

In addition to waking up in the middle of the night, 39% of the respondents in the OnePoll survey reported feeling exhausted on awakening in the morning—and this complaint was more frequent among the young and middle-aged than in adults 55 and older. This suggests that quite a few Americans aren’t getting the amount or type of sleep we need.

Reason #1: Bathroom Calls

About 74% of the respondents reported that one reason for their middle-of-the-night wake-ups was the need to go to the bathroom. This is not surprising given the ages of the respondents (43% were 55 and older). But not only does having to void several times at night decrease sleep quality. It also puts you at greater risk for developing chronic insomnia.

So if your nighttime wake-ups are due to an overactive bladder, have a look at the blog I wrote last December on ways to cut down on the need for bathroom calls at night.

Also, a few preliminary studies I’ve seen in the past year suggest that supplements containing pumpkin seed extract, alone or in combination with soy isoflavones, may reduce symptoms of overactive bladder. If you’re game to try the pumpkin seed extract/soy isoflavone supplements, keep in mind that like most plant-based medicines, they may need to be taken a few weeks before you notice effects.

Reason #2: Temperature Changes at Night

About 36% of the respondents reported usually waking up in the middle of the night because they were too hot, and about 19% reported awakening because they were too cold.

Some of this may have to do with changes in core body temperature at night. From a high in the evening, your temperature falls by about 1.5 degrees Fahrenheit during the night, bottoming out a few hours before wake-up time and then rapidly rising again. No wonder that during the first part of the night you’re piling the covers on and in the last part, throwing them off.

Especially if you tend to sleep hot, my blog on tips for overheated sleepers may help.

Reason #3: Stress and Anxiety

Finally, 32% of all survey respondents blamed their nighttime wake-ups on stress and anxiety—which isn’t so surprising. But the suggestion that the youngest adults are the most prone to stress-related wake-ups gives pause.**

Pressure to get into a good college, find the right job, land securely among the “haves” rather than the “have-nots” at a time when in the United States the haves and have-nots are growing farther and farther apart . . . Is young adulthood more stressful now than in times past?

What do you think?

* Results of this poll, which I accessed on 12/4/2015, are no longer available online. Use the contact form on the menu bar if you’d like me to send you a copy.

** Only 37 adults aged 18 to 24 participated in the survey, so the findings on young adults may not be very reliable. Yet other research has shown at least that the number of young adults who experience insomnia is actually quite high.

L-Tryptophan May Help You Sleep

Interesting but dangerous: that’s what I heard about L-tryptophan supplements for several years. Research starting in the 1960s was showing that L-tryptophan might be an effective remedy for insomnia.

Then came the tryptophan-related outbreak of eosinophilia-myalgia syndrome (EMS) in 1989, killing 37 people and sickening thousands. The United States subsequently banned the supplements, and research on L-tryptophan and sleep came to a halt.

Now reviewers of alternative treatments for insomnia are again mentioning L-tryptophan as a substance of interest. Here are the pros and cons.

Mild Insomnia may respond to treatment with L-tryptophan supplementsInteresting but dangerous: that’s what I heard about L-tryptophan supplements for several years. Research starting in the 1960s was showing that L-tryptophan might be an effective remedy for insomnia.

Then came the tryptophan-related outbreak of eosinophilia-myalgia syndrome (EMS) in 1989, killing 37 people and sickening thousands. The epidemic was traced to contaminated L-tryptophan produced by a single Japanese company, but the United States banned L-tryptophan supplements from 1990 to 2001. Research on L-tryptophan and sleep came to a halt.

Now reviewers of alternative treatments for insomnia are again mentioning L-tryptophan as a substance of interest. Here are the pros and cons.

What It Is

L-tryptophan is an essential amino acid the body requires in order to synthesize proteins and other key molecules. It’s a precursor to serotonin, a neurotransmitter important to sleep, and melatonin, a hormone secreted at night.

Humans cannot produce L-tryptophan on their own. So it has to be gotten from food (or supplements). In one experiment, depriving insomniacs of L-tryptophan made their insomnia worse, as recorded by studies conducted in a sleep lab. Low levels of tryptophan resulted in sleep that was lighter and less continuous. This suggests that something about L-tryptophan facilitates sleep.

Laboratory tests show that tryptophan administered at night increases concentrations of both serotonin and melatonin in the brain. So its sedative effects are probably due to its enhancement of the melatonin or the serotonin system.

Randomized Controlled Trials

Taken at bedtime in amounts of 1 to 4 grams, L-tryptophan has been found to be at least somewhat effective for people with insomnia in several studies, including double-blind trials. But results from three randomized controlled trials, considered the highest standard of evidence, are mixed.

  1. In an early study of 96 “serious insomniacs,” weeklong treatment with tryptophan was compared with weeklong use of a placebo. No differences were noted during the tryptophan treatment—but participants taking tryptophan reported falling asleep more quickly than normal in the week following treatment.
  2. In a subsequent study, people with severe chronic insomnia were divided into two groups: one group took tryptophan nightly for 4 weeks, followed by 4 weeks of placebo; the other began with placebo and after 4 weeks swtiched to tryptophan. Group A reported improved sleep quality while taking the tryptophan; group B did not.
  3. In a more recent study, tryptophan from squash seeds and pharmaceutical-grade tryptophan, both in the form of food bars, significantly improved sleep duration and sleep quality in study participants compared with a food bar containing carbohydrate alone. The tryptophan from squash seeds outperformed the pharmaceutical-grade tryptophan in reducing time awake at night.

Well yes, these results are underwhelming.

Consider This, Too

Other research is more encouraging. L-tryptophan in some studies has reduced participants’ sleep latency and cut down on nighttime wake-ups. Reviewers make these comments:

  • The best results seem to occur in cases of mild insomnia with long sleep latency.
  • People with more severe forms of insomnia may need to take L-tryptophan for several nights before they notice improvement in their sleep.
  • In people with sleep maintenance insomnia, L-tryptophan may be more effective for those who wake up several times a night rather than for those who awaken less frequently.           

Foods High in Tryptophan

As alternative treatments for insomnia go, L-tryptophan supplements are now considered safe and relatively free of side effects. (For pregnant and breast-feeding women, however, L-tryptophan is listed as “likely unsafe.”)

But you may be able to get most of what you need in your daily diet. Meat, fish, and seafood contain lots of of L-tryptophan; eggs, cheese, and milk contain quite a bit, too. The following foods are also high in L-tryptophan:

  • soybeans and soy products
  • sesame seeds
  • seaweed
  • spinach
  • mushrooms, wild and garden variety
  • turnip and mustard greens
  • asparagus

One last caveat. By itself, L-tryptophan does not cross the blood-brain barrier. Combining an L-tryptophan-rich food with a carbohydrate greatly improves L-tryptophan uptake in the brain. So for your evening snack, have your cheese on a cracker and your tofu with rice.

If you’ve tried L-tryptophan supplements, what effect did they have on your sleep?

Insomniacs: Are We Dreaming About Sleeplessness?

Rapid eye movement sleep (REM sleep) is when most dreams occur. Episodes of REM sleep also help defuse negative emotions and improve the learning of motor skills.

Until recently, insomnia wasn’t thought to be a problem of REM sleep. Insomnia, the thinking went, was caused mainly by phenomena occurring—or failing to occur—during quiet, or non-REM, sleep: insufficient deep sleep, for example, or wake-like activity occurring in other stages of non-REM sleep, resulting in insufficient or poor sleep.

In the past few years, though, REM sleep has become a suspect in the quest to identify what causes people to wake up frequently in the middle of the night and too early in the morning. (This type of insomnia is called sleep maintenance insomnia). Here’s more about this intriguing proposition.

Insomnia sufferers may be remembering dreams of sleeplessness rather than lying awake for hoursRapid eye movement sleep (REM sleep) is when most dreams occur. Episodes of REM sleep also help defuse negative emotions and improve the learning of motor skills.

Until recently, insomnia wasn’t thought to be a problem of REM sleep. Insomnia, the thinking went, was caused mainly by phenomena occurring—or failing to occur—during quiet, or non-REM, sleep: insufficient deep sleep, for example, or wake-like activity occurring in other stages of non-REM sleep, resulting in insufficient or poor sleep.

But in the past few years, REM sleep has become a suspect in the quest to identify what causes people to wake up frequently in the middle of the night and too early in the morning. (This type of insomnia is called sleep maintenance insomnia). Here’s more about this intriguing proposition.

Do Insomniacs Really Underestimate Sleep Time?

It’s said that insomniacs tend to underestimate the amount of sleep they get. Polysomnography (PSG), the test conducted in the sleep lab, often shows that insomnia sufferers are sleeping more than they think.

Investigators now agree that PSG, as conducted and scored in standard fashion, is too crude a measure to capture what’s going on in disturbed sleep. Finer measures are needed. One such measure involves counting the number of arousals and micro-arousals—brief awakenings—during sleep.

In a seminal study published in 2008, a team of German scientists used PSG, sleep time estimates of study participants, and micro-arousal analysis to ascertain what the differences were between insomniacs and good sleepers. The results showed that compared with good sleepers, insomniacs

  • Got less non-REM and REM sleep overall
  • Experienced more micro-arousals during both non-REM and REM sleep, but the number of micro-arousals during REM sleep was more pronounced: about 2 to 3 times larger than the number experienced by good sleepers. Further, the more REM sleep insomniacs got, the greater was the mismatch between their sleep time as recorded by PSG and the sleep time reported by the insomniacs themselves.

These results suggest that (1) it may be disturbances that occur during REM sleep, more so than during non-REM sleep, that account for the discrepancy between PSG-measured sleep and insomniacs’ perception of their sleep, and (2) disturbed REM sleep may be the main problem for people with sleep maintenance insomnia.

How Disturbed REM Sleep Might Develop

Not much brain activity occurs during non-REM sleep. But REM sleep is marked by a mix of arousal in some parts of the brain and quiescence in other parts. The same group of scientists in a 2012 paper describe REM sleep as “a highly aroused ‘paradoxical’ sleep state requiring a delicate balance of arousing and de-arousing brain activity.” This brain activity involves many different groups of neurons. The over- or underexpression of any of these groups might disturb that “delicate balance,” causing fragmented REM sleep.

This idea fits in with the dominant explanation for chronic insomnia: it’s a manifestation of hyperarousal, which may come about in part due to stress. Stressful life experiences often cause sleep loss. If the poor sleep continues, then sleeplessness and worry about the daytime consequences themselves become stressors and insomnia becomes a chronic affair. The chronic stress accompanying chronic insomnia also leads to changes in the brain. These changes could cause REM sleep fragmentation and disrupted or poor sleep.

Remembering Dreams of Sleeplessness

The idea of REM sleep fragmentation as a driver of sleep maintenance insomnia also fits with the continuity hypothesis of dreaming, which posits that the content of dreams comes from everyday concerns. Not much research exists on the content of insomniacs’ dreams. What is known is summarized in a paper published in Sleep Medicine Reviews:

  • Compared with normal sleepers, insomniacs tended to experience themselves more negatively in their dreams
  • Problems that occurred in dreams were related to current real-life concerns
  • Health problems also appeared more frequently in insomniacs’ dreams.

People with chronic insomnia are prone to worry about sleep loss and its consequences, and these concerns might well dominate the content of our dreams. And if we’re experiencing lots of micro-arousals as we’re dreaming, the content of those dreams would be more accessible to conscious recall. Instead of actually lying awake for hours at night, sleep maintenance insomniacs might be awakening briefly but often to dreams of sleeplessness, making it feel like we’re sleeping less than we are.

Precisely how REM sleep becomes fragmented remains to be seen. But the finding that REM sleep is significantly unstable in sleep maintenance insomniacs is a step in the right direction.

Does the idea of REM sleep instability as a driver of sleep maintenance insomnia seem plausible to you?