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.

Early Treatment of Insomnia May Improve Mental Health

Insomnia and mental health problems go hand in hand. It’s firmly established now that insomnia can be a causal factor in depression and that treatment for insomnia can improve both sleep and mood.

A new study shows that insomnia may also be a causal factor in psychotic experiences such as paranoia and hallucinations, and that CBT for insomnia (CBT-I) may lead to better mental health. Here’s a quick look at the research and what it suggests for us.

Web-based cognitive behavioral therapy for insomnia improves sleep & moodInsomnia and mental health problems go hand in hand. It’s firmly established now that insomnia can be a causal factor in depression and that treatment for insomnia can improve both sleep and mood.

A new study shows that insomnia may also be a causal factor in psychotic experiences such as paranoia and hallucinations, and that CBT for insomnia (CBT-I) may lead to better mental health. Here’s a quick look at the research and what it suggests for us.

Sleep and Mood: An Intimate Relationship

People with mood disorders and other mental health problems often experience insomnia. Until recently their trouble sleeping was viewed as a symptom or a consequence of the mental health problem. Successful treatment of that problem would take care of the insomnia, too—or so they thought.

Then along came research that upset the apple cart. It showed that insomnia was sometimes a causal factor in depression, and that treatment with CBT for insomnia (CBT-I) helped to resolve both problems better than treatment for depression alone. This led to a related question: could other psychiatric symptoms linked with insomnia—paranoia, hallucinations, anxiety, mania—be triggered in part by insomnia and could treatment with CBT-I head off their development?

A Large-Scale Study

Paranoia and hallucinations have strong links to insomnia. Researchers in the UK recruited 3,755 university students with insomnia from 26 different college campuses to see if treating their insomnia with CBT-I would lessen their risk of experiencing these psychotic symptoms.

Randomly the researchers divided student participants into two equal groups. One served as a control group. Students in the other group participated in an individualized online insomnia treatment program called Sleepio.

Similar to other research-based online insomnia treatments (SHUTi and CBT for Insomnia, for example), Sleepio is a 6-week program that delivers CBT-I over the internet. It includes behavioral components such as sleep restriction and stimulus control; cognitive components that challenge unhelpful beliefs; and education about sleep and sleep hygiene.

Student participants in both groups also took a battery of pencil and paper tests at four different times during the 6-month study period to assess the severity of their insomnia symptoms and the state of their mental health. Statistical analysis of the data included looking at whether reductions in insomnia symptoms correlated with better mental health outcomes.

Insomnia Treatment Improves Sleep, Reduces Psychotic Symptoms

Here are the main results, all statistically signficant. Compared with participants in the control group, participants who underwent the Sleepio treatment ended the program with

  • greatly improved sleep
  • fewer experiences of paranoia and hallucinations

The Take-Away

The results of this relatively large study led to the following claims:

  1. Online insomnia treatment programs like Sleepio work for university-age students with trouble sleeping. They’re inexpensive and can be accessed at home.
  2. While insomnia might not be the principal cause of psychotic experiences, it may well be a contributing cause.
  3. CBT-I may have promise as an early intervention for some psychiatric problems.

Caveats for the Sleepless Whether or Not Mental Health Is an Issue

CBT-I, for all its effectiveness, involves commitment to a weeks-long process and the discipline to follow a rigorous set of guidelines. In this study there was a 50% drop-out rate among participants assigned to the Sleepio program—higher than the dropout rate for the control group. Feeling sleep deprived and lacking stamina, some insomniacs may be unsuccessful at completing a CBT-I program in the absence of face-to-face coaching and encouragement from a trained sleep therapist.

But 50% of the participants stuck with the Sleepio program long enough to reap sleep benefits. This success rate is comparable to that found in research on other web-based insomnia treatment programs.

Our options do not stop with online treatment programs. I’ve found it’s also possible to improve sleep by following instructions in books about CBT-I (see, for example, The Insomnia Workbook by Stephanie Silberman, The Insomnia Answer by Paul Glovinsky and Arthur Spielman, or chapter 8 of my book, The Savvy Insomniac). I myself used CBT-I to improve my sleep after reading a training guide for sleep therapists (Cognitive Behavioral Treatment of Insomnia: A Session-by-Session Guide by Michael Perlis and colleagues).

Regardless of how it’s accessed, CBT-I remains our best defense against sleepless nights and draggy days—and it may also preserve our mental health and well-being.

If you’ve tried CBT-I, how did you access treatment and how useful was it in helping to improve your sleep?

Tai Chi When Insomnia Isn’t the Only Problem

Insomnia combined with other health problems is bound to cause distress.

But help is at hand. New research shows that tai chi reduced insomnia symptoms in breast cancer survivors, suggesting that it may help with insomnia linked to other health problems, too.

Tai chi may improve sleep for insomnia sufferers with other health problemsA reader wrote yesterday asking for advice: “I’ve been reading through your website but have yet to see an article on how to manage sleep with chronic illness. I’m currently experiencing health challenges that are keeping me awake at night. What would you recommend for people experiencing health issues, especially moderate to severe ones?”

Insomnia combined with other health problems is bound to cause distress. But help is at hand. New research shows that tai chi reduced insomnia symptoms in breast cancer survivors, suggesting that it may help with insomnia linked to other health problems, too.

When Insomnia Is Not the Only Problem

Sometimes insomnia is the only health problem a person has. But insomnia more commonly occurs in conjunction with other health issues—everything from mood disorders and chronic pain to gastrointestinal problems and heart disease.

Part of the solution when you’re in this situation (sometimes referred to as comorbid insomnia) lies in getting treatment for the associated health problem. This will involve consulting a medical or psychiatric specialist.

But even when treatment is successful at controlling other health problems, trouble sleeping often persists. Women successfully treated for breast cancer have twice the rate of insomnia as occurs in the general population, as well as depression and fatigue. This is hardly surprising: A diagnosis of breast cancer is distressing in and of itself, never mind the invasive (although often effective) treatment options. But then you never know if or when the cancer might come back. Such chronic health concerns take an emotional toll that can interfere with sleep.

CBT for Insomnia Can Help

Cognitive behavioral therapy (CBT) is the gold standard in treatment for insomnia these days. This combination of sleep restriction, stimulus control, and talk therapy has been shown to be an effective treatment for insomnia in cancer survivors. Research shows it’s also effective in relieving insomnia in people with depression and people with other psychiatric and medical conditions.

But CBT for insomnia is not widely available nor can everyone afford it. Besides, it can be challenging to adhere to the protocol. CBT does not suit everyone.

UCLA investigators wanted to find a more accessible, less expensive type of therapy for breast cancer survivors experiencing insomnia that would equal CBT in efficacy. So they conducted a randomized, partially blinded study pitting CBT against tai chi.

Why Tai Chi?

Tai chi, a practice involving slow, flowing movement combined with meditation and deep breathing, is said to alleviate stress and anxiety and promote energy and stamina. In the words of the study’s authors, tai chi emphasizes “control over physical function and arousal-related responsiveness . . . through the mindful performance of repetitious, nonstrenuous, slow-paced movement.”

This type of activity might have an effect on sleep. And in fact a handful of studies have shown that tai chi does indeed relieve insomnia symptoms.

So investigators recruited 90 breast cancer survivors, aged 42 to 83 years, who were experiencing insomnia, depression, and fatigue. Half of them then received three months of weekly instruction in CBT for insomnia. The other half received three months of weekly instruction in a westernized form of tai chi called tai chi chih.

Impressive Results

At 15 months following the start of treatment (one year after treatment ended), nearly half of the participants in both groups showed marked improvement in their sleep, or complete or nearly complete remission of their insomnia symptoms. Both groups also experienced a robust reduction in fatigue severity and depression.

The novelty of this result is that for these survivors of breast cancer, the practice of tai chi chih resulted in sleep improvements equivalent to those obtained with CBT. Tai chi may be similarly useful for insomnia sufferers with other distressing health problems.

Lowering Arousal, Reducing Inflammation

The mechanisms by which tai chi relieves insomnia symptoms aren’t understood. But research has shown that tai chi:

  • Cuts down on arousal of the sympathetic nervous system. The sympathetic nervous system becomes active when you detect a threat, increasing vigilance and triggering bodily preparations to fight or flee.
  • Reduces inflammation. Inflammation is part of the body’s response to infection and tissue damage and is necessary to the healing process. But when inflammation becomes chronic it leads to disease.

Both arousal and inflammation have a negative effect on sleep. So it follows that a practice such as tai chi, which reduces them, might help.

Tai chi is worth checking into for people with comorbid insomnia and other distressing health conditions. Classes are offered in many locales. You can even learn tai chi by watching YouTube videos or using a smartphone app.

If you’ve practiced tai chi, what effect, if any, did it have on your sleep?

An Ayurvedic Herb for Better Sleep

Might Ayurvedic medicine—traditional medicine practiced in India for 3,000 years—offer an effective treatment for insomnia?

If you’re looking for an alternative treatment vetted by scientists in controlled clinical trials, the answer is no. But an Indian herb called ashwagandha is receiving attention as a substance that might help people with several health conditions, including chronic stress, anxiety, and memory loss. It’s also being studied as a possible sleep aid. Here’s more about it.

Insomnia may respond to treatment with ashwagandhaMight Ayurvedic medicine—traditional medicine practiced in India for 3,000 years—offer an effective treatment for insomnia?

If you’re looking for an alternative treatment vetted by scientists in controlled clinical trials, the answer is no. But an Indian herb called ashwagandha is receiving attention as a substance that might help people with several health conditions, including chronic stress, anxiety, and memory loss. It’s also being studied as a possible sleep aid. Here’s more about it.

Ashwagandha (Withania somnifera)

Ayurvedic medicine is a holistic healing system. Patients are generally prescribed a combination of herbs, special diets, and daily practices aimed at promoting overall health rather than eliminating a specific problem like insomnia.

But the Latin somnifera means sleep-inducing, and ashwagandha powder, prepared from the root, leaves, or whole plant and taken orally, has been prescribed to improve sleep for centuries. A handful of laboratory studies on rodents have provided evidence for ashwagandha’s sleep-inducing effects. Results of some studies suggest that ashwagandha leaf extract may also protect rats from the consequences of sleep deprivation.

Authors of a recently published paper in PLOS ONE have identified a specific component of the ashwagandha leaf that puts mice to sleep. Following is a summary of their findings.

An Active Component That Promotes Sleep

Biologically active components in ashwagandha include withanolides—naturally occurring steroids—and triethylene glycol, or TEG. TEG is currently used in various manufacturing processes, but how it impacts biological systems is largely unknown. In this study, investigators wanted to find out if one or the other of these substances had sleep-inducing effects.

Via a complicated extraction process, the researchers isolated each of these compounds, mixing them with alcohol and water so they could be administered orally to mice. Here are the results:

  • Compared with the alcoholic medium alone, the alcoholic extract containing a high amount of active withanolides had no effect on the sleep–wake system of the mice.
  • Compared with water alone, the extract containing lots of TEG induced a significantly greater amount of non-REM, or quiet, sleep—without affecting the amount or nature of REM sleep.
  • Commercially available TEG was also administered to the mice in 10, 20, and 30-mg doses. The larger the dose, the more non-REM sleep the mice got over a 12-hour period and the more quickly they fell asleep.

The authors conclude that while low to moderate levels of TEG clearly induce sleep in laboratory animals, possible “toxicological properties of TEG need to be studied in detail before its used is advised in humans.”

Meanwhile, Is Ashwagandha Safe for Humans?

It depends on where you ask the question. Indian practitioners of Ayurvedic medicine have been prescribing it for centuries. A handful of scientific studies also attest to the safety of this herb when used short term in therapeutic doses. (Long-term effects are unknown.)

But an article in Medline Plus lists a number of safety concerns. People who are pregnant and breast feeding, who have diabetes, or who have an auto-immune disorder should steer clear of ashwagandha. The herb can interact with various medications and supplements, too.

For a definitive reading on whether ashwagandha could work as a treatment for insomnia we’ll have to wait and see. But it’s widely available as a dietary supplement in powder, capsule, and tablet forms. Of course, dietary supplements are less well regulated by the FDA than prescription medications. Quality is not assured.

But if you’re looking for better sleep and tempted to try ashwagandha, consult a practitioner of Ayurvedic medicine or a naturopath about whether the herb might have something to offer you.

Insomnia and Your Genes

If you suspect there’s a biological component to your insomnia, you’re probably right. Although talk about insomnia is mostly confined to situational triggers as well as habits and attitudes that keep insomnia alive, all models of chronic insomnia assume the existence of predisposing factors. Some of these factors may be inherited at birth.

What evidence is there for genetic involvement in insomnia, and where might it lead? A review published recently in Brain Sciences brings us up to date.

Genetic variants may be an underlying factor in insomniaIf you suspect there’s a biological component to your insomnia, you’re probably right. Although talk about insomnia is mostly confined to situational triggers as well as habits and attitudes that keep insomnia alive, all models of chronic insomnia assume the existence of predisposing factors. Some of these factors may be inherited at birth.

What evidence is there for genetic involvement in insomnia, and where might it lead? A review published recently in Brain Sciences brings us up to date.

Family and Twin Studies

The number of family studies is small—five—and one reason may be that in family studies it’s hard to tease apart genetic effects from the effects due to shared environment. But overall these studies suggest that insomnia tends to run in families. A recent study found that the children of parents with high levels of stress related insomnia were more likely to experience higher cognitive–emotional hyperarousal.

Twin studies are more numerous (20). By comparing correlations between identical twins (who share 100% of their genes) and fraternal twins (who share 50% of their genes on average) who are raised together, researchers can more easily sort out which effects are genetic and which are due to a shared environment. Based on twin studies, insomnia heritability estimates range from 22% to 59% in adults, depending on the type of study and which sleep variable was assessed (sleep duration? trouble falling asleep at the beginning of the night? subjective sleep quality?).

Recently, a large twin study by Lind and colleagues provided new evidence that

  • there is a larger genetic contribution to insomnia in women (59%) than in men (38%), and
  • in adults, insomnia heritability is stable across time.

Researchers assessed the heritability of insomnia through childhood and adolescence in another twin study. In youth, too, they found that genetic influences on insomnia are stable across time.

Studies of Candidate Genes

The one drawback of twin studies is that they don’t point to which genes confer vulnerability to (or protection from) insomnia. But based on knowledge of specific genes that figure in other disorders (notably psychiatric disorders and other sleep disorders), scientists can guess which genes might be involved in insomnia and then conduct candidate gene studies on them. The aim of such studies is to compare variation in a gene suspected of causing insomnia in people with and without insomnia.

One gene that figures in the transport of serotonin (5-HTTLPR) has been studied for its relevance to depression and to insomnia. Huang and colleagues found that variation in this gene

  • significantly affected people’s vulnerability to insomnia, and
  • significantly predicted people’s reactivity to job-related stress.

Other candidate genes have been studied, including some that increase the risk of insomnia and others that protect against it. But few genes have been studied in detail and replication studies are still lacking.

Genome Wide Association Studies (GWAS)

GWAS allow scientists to examine millions of variants across the genome at the same time. Only four GWAS of genes potentially involved in insomnia have been conducted so far. But now that genotyping has become less expensive and management of data is easier, GWAS are the wave of the future.

One GWAS of interest was conducted by Australian researchers looking at insomnia and several aspects of sleep in a sample of twins. They found no genome-wide variants of significance.

But the most prominent finding was that a variant of CACNA1C, a gene associated with bipolar disorder, was also associated with sleep quality and sleep latency (the amount of time it takes to fall asleep). The relationship between CACNA1C and sleep quality was later replicated in a British study, suggesting that this gene may indeed be involved in insomnia.

CACNA1C codes for a mechanism that excites neurons and leads to the release of neurotransmitters. If this excitation occurs in neurons that promote wakefulness or neurons that inhibit sleep, this could lead to hyperarousal and trouble sleeping, in turn increasing a person’s risk of developing insomnia.

Why This Is Important

There hasn’t been much discussion of the factors that predispose us to insomnia—at least not in the popular press—and this is partly because not a lot is known about them. And at present little can be done to alter genetic traits.

But knowledge of the genetic underpinnings of insomnia will be increasingly important to the prevention and treatment of insomnia in the future. It could enable doctors to know which insomniacs will likely respond to treatment with cognitive behavioral therapy and which ones will not, or which medications will likely be effective and which will not.

Early intervention and prevention may also be possible once the risk and protective genes for insomnia are known. Further down the line, it may be possible to alter the expression of risk genes (with drugs that target gene regulation) or use gene therapy to replace defective genes.

All this may not help us manage insomnia now. But it’s heartening to know that scientists are pursuing knowledge that could take some of the guesswork out of treatment for insomnia and eventually render the treatments available today—imperfect as they all are—obsolete.

Comments, anyone?

Could Pumpkin Seeds + Carbs = Better Sleep?

Let’s begin with a caveat: no organic sleep aid on the market has been shown to cure insomnia.

But if you like warm, nonalcoholic, caffeine-free liquids, and if drinking a beverage is part of your evening routine, you might be interested in trying Zenbev Drink Mix. Here’s more information about it.

Insomnia sufferers may want to try a sleep aid called Zenbev Drink Mix, made from pumpkin seedsLet’s begin with a caveat: no organic sleep aid on the market has been shown to cure insomnia.

But if you like warm, nonalcoholic, caffeine-free liquids, and if drinking a beverage is part of your evening routine, you might be interested in trying Zenbev Drink Mix. Its claim as a sleep aid and alternative treatment for insomnia is based on a study showing that food bars made from the same ingredients significantly reduced insomnia subjects’ time awake at night.

Here’s more information about it.

What Is Zenbev Drink Mix?

It’s made from pumpkin seeds that are cold-pressed to remove the oil and made into pumpkin seed flour. The flour is then combined with dextrose (the sugar found in plants), rice starch (a carbohydrate), and guar gum (a binder–thickener); flavored with chocolate or lemon; and sold as a powder, to be mixed with warm milk or warm water. It’s touted as promoting “a natural and healthy sleep.”

A Tryptophan–Carbohydrate Combination

Research suggests there may be grounds for this claim. Like other protein sources—turkey, fish, milk—pumpkin seeds are high in tryptophan, an essential amino acid. Tryptophan is a precursor to melatonin, a hormone secreted at night. Your melatonin levels start to rise a few hours before bedtime, which helps you fall and stay asleep. Tryptophan is also a precursor to serotonin, a neurotransmitter the body eventually converts into melatonin.

But tryptophan has to cross the blood–brain barrier to exert its sleep-inducing effects. It competes with other amino acids to cross that barrier, so a drink high in tryptophan alone would not have much effect on sleep.

Adding a carbohydrate to the mix might help. It would promote the release of insulin, inhibiting production of competing amino acids or diverting them into muscle. With less competition at the gate, more tryptophan would be expected to cross the blood–brain barrier and begin its conversion into serotonin and melatonin, in turn promoting sleep.

Effects on Sleep

To test the effects of the pumpkin seed–carbohydrate combination on sleep, Biosential, the company that makes Zenbev Drink Mix, set out to conduct a randomized controlled trial, enrolling 57 people with insomnia.

Forty-nine participants completed the 3-week study. Each week they were randomly administered 3 different food bars. One week, the food bars contained deoiled pumpkin seed flour mixed with carbohydrate. Another week, the food bars contained pharmaceutical-grade tryptophan mixed with carbohydrate. In another week, the food bars contained carbohydrate only.

The bars containing deoiled pumpkin seed and those containing pharmaceutical-grade tryptophan led to significant improvements in sleep, as reported by study participants. The bars made of carbohydrate alone led to some improvement, too.

Measured objectively, the pharmaceutical-grade tryptophan outperformed the deoiled pumpkin seed when it came to increasing sleep duration. But the bar containing the deoiled pumpkin seed-carbohydrate preparation was the only treatment to significantly cut down on wake time after sleep onset.

The Take-Away

Offering the results of a single trial as proof that a treatment works is better than offering no results at all. Yet the study would have to be repeated—with Zenbev Drink Mix instead of food bars—to substantiate the claim that this beverage can actually improve insomniacs’ sleep.

Still, enough evidence points to tryptophan’s helpful effect on sleep that Zenbev Drink Mix may be worth trying, especially if you’re looking for alternative treatments for insomnia and interested in exploring the idea that dietary changes might help. The product is sold in the United States, Canada, and Europe.

Acupuncture for Insomnia: An Update

This summer I saw a cousin of mine who lives in San Francisco. He was using acupuncture for insomnia and happy with the results.

I’ve always wondered about acupuncture as a potential treatment for insomnia, so now and then I check the literature. Here’s a summary of recent thinking about it.

Insomnia may respond to acupuncture treatmentsThis summer I saw a cousin of mine who lives in San Francisco. He was using acupuncture for insomnia and happy with the results.

Back when I lived on the West Coast, I tried acupuncture for help in managing stress (the usual trigger for my insomnia) and also got results. A single session of acupuncture—followed by use of foul-smelling herbs I was to boil and drink as tea—really helped to calm me down.

I still wonder about acupuncture as a potential treatment for insomnia, so now and then I check the literature. Here’s a summary of recent thinking about it.

Why Might Acupuncture Work for Insomnia?

The underlying problem for people with insomnia is said to be hyperarousal. Insomniacs’ brains are unusually active at night, suggesting hyperarousal of the central nervous system. Whether and how acupuncture could calm the brain is yet to be worked out.

There’s also evidence that insomniacs are more physiologically aroused than normal sleepers. We tend to have elevated metabolic rates and, at night, lower heart rate variability, suggesting involvement of the autonomic nervous system (the system controlling things we can’t consciously direct, such as breathing and heartbeat). Hyperarousal in insomniacs suggests too much activity of the sympathetic branch of the autonomic nervous system (associated with stress and the fight-or-flight response).

Acupuncture has a direct effect on the autonomic nervous system, say Wei Huang and colleagues at the Emory University School of Medicine. It’s been shown to influence known indicators of autonomic activities such as blood pressure, heart rate, and heart rate variability. It’s used to manage cardiovascular diseases such as hypertension and cardiac arrhythmia. It’s also been shown to regulate neurotransmitters and hormones important to the sleep–wake cycle.

Acupuncture may work by tamping down the physiological arousal that makes it harder for insomniacs to go to sleep and stay asleep at night. But how it does so remains unknown.

What About Clinical Trials?

Some reviewers have found that acupuncture has overall positive effects on sleep. Study participants have reported that acupuncture helps them:

  • Fall asleep more quickly
  • Sleep more efficiently
  • Sleep longer
  • Have better-quality sleep

Other reviewers have not found convincing evidence that acupuncture helps people sleep longer or better. A survey of literature through 2011 concludes that there’s not enough “high-quality evidence” either to support or refute acupuncture as an effective treatment for insomnia.

A Standard Hard to Meet

By high-quality evidence reviewers often mean the results of double-blinded, randomized clinical trials—the gold standard for studies of a treatment on human beings. This type of study involves comparing an active treatment to a sham treatment (a medication to a placebo pill, for example), assigning participants to either the active treatment or the placebo treatment in a random manner, and making sure that neither participants nor clinicians know who’s getting what.

This standard is hard to meet in studies of acupuncture, David Mischoulon says in a commentary in the Journal of Clinical Psychiatry. Fake acupuncture—needles placed in positions known not to affect sleep, or acupuncture with nonpenetrating needles—is often used as a sham treatment. But acupuncture practitioners always know whether they’re administering active or fake treatment and may subtly communicate this to trial participants, compromising study results.

Also, the contribution of the “placebo effect” to acupuncture study results is apparently considerable. Says Mischoulon, “We found that believing that one was receiving an active intervention seemed to correlate with clinical improvements more so than which intervention was actually received.”

Mischoulon and others have proposed different types of sham treatments for use in future acupuncture trials. Hopefully they will supply the high-quality evidence needed to settle the issue of whether and in which situations acupuncture might work as a treatment for insomnia.

Different Acupuncture Points

Meanwhile, other researchers have trained their attention on which acupuncture points seem to help insomniacs the most. These are believed to have calming effects:

  • PC-4 Ximen (in the middle of the forearm with palm side up)
  • GV-14 Dazhui (on the back at the base of the neck)
  • PC-6 Neiguan (just above the wrist with palm side up)
  • EX-HN1 Sishencong (at the top of the head)
  • BL-15 Xinshu (on the upper back just right of the spine)

In summary, the evidence on acupuncture’s effectiveness for insomnia is still mixed. But it’s got one big advantage over sleeping pills. Its safety and lack of side effects have been demonstrated again and again.

If you’ve tried acupuncture for relief from insomnia, please let us know how it worked.

Tart Cherries: Helpful to Sleep but Harder to Find?

First, the good news: a small body of research suggests that tart cherry juice holds promise as an alternative treatment for insomnia, especially in older adults.

Now for the bad news: tart cherry juice, already pricey, is set to become pricier still as growers weigh whether to give up on cherries and plant apple trees instead. Here’s more on the benefits of tart cherry juice for sleep and why it may soon become scarce.

Insomnia, alternative treatment tart cherry juice not so plentifulFirst, the good news: a small body of research suggests that tart cherry juice holds promise as an alternative treatment for insomnia, especially in older adults.

Now for the bad news: tart cherry juice, already pricey, is set to become pricier still as growers weigh whether to give up on cherries and plant apple trees instead. Here’s more on the benefits of tart cherry juice for sleep and why it may soon become scarce.

Sleep Benefits of Tart Cherry Juice

A handful of studies conducted on the effects of tart, or Montmorency, cherry juice on sleep suggest it may be helpful for people with insomnia:

  • It may help you sleep longer. In a randomized controlled trial (RCT) published in 2012, drinking tart cherry juice concentrate mixed with 8 oz. of water twice daily for 7 days increased the total sleep time of 20 healthy volunteers by an average of 39 minutes.
  • Seven older adults with insomnia slept over an hour longer after 2 weeks of drinking 8 oz. of tart cherry juice twice a day. Results of a randomized crossover trial presented at the 2014 meeting of the American Society of Nutrition (still unpublished) showed that participants’ total sleep time increased by an average of 84 minutes.
  • Tart cherry juice may cut down on nighttime wake-ups and improve sleep quality. In an RCT published in 2010, drinking 8 oz. of tart cherry juice twice daily for 2 weeks significantly cut down on wake-ups and insomnia severity in 15 older adults with sleep maintenance insomnia.
  • The same twice-daily regimen of tart cherry juice had similar effects on the sleep of 30 healthy young, middle-aged, and older adults in a study published in 2013. Older participants’ sleep improved the most.

The evidence is not conclusive: these studies were small and only two looked specifically at the effects of tart cherry juice on people with insomnia. Still, unless you dislike or can’t tolerate tart cherries, drinking tart cherry juice twice a day is worth consideration as an alternative treatment for persistent insomnia.

Melatonin and Tryptophan-Enhancing Effects

Montmorency cherries are rich in melatonin, a sleep-friendly hormone secreted by the pineal gland at night. Melatonin production often falls off as people age, and lower levels of endogenous melatonin can make it harder to get to sleep and stay asleep at night. Tart cherry juice may exert its soporific effects mainly by increasing levels of melatonin at night.

Another mechanism by which tart cherry juice may benefit sleep can be found in the effect it has on tryptophan. Tryptophan is an amino acid humans need but cannot produce themselves, so it must be gotten in food. Tryptophan is a precursor to both melatonin and serotonin, a neurotransmitter important to sleep. Researchers who conducted the 2014 study found that tart cherry juice inhibited the degradation of tryptophan, thereby making more of it available for serotonin synthesis.

The sleep benefits of Montmorency cherry juice may be due to both its melatonin and tryptophan-enhancing effects.

Climate Change and Market Forces

But some fruit growers are now on the verge of abandoning cherry orchards and planting apple trees instead. Two factors are behind the change, according to an Interlochen Public Radio report last week:

  1. Most of the nation’s tart cherries are grown in northern Michigan, where almost the entire cherry crop was lost in 2012 due to an early spring followed by over 2 weeks of below-freezing temperatures. Cherry trees planted in Michigan are actually shipped from nurseries in the Pacific Northwest. Extreme weather events there have killed off thousands of cherry saplings. Michigan orchardists who want to continue producing cherries now can’t buy enough young cherry trees to replenish aging stock.
  2. Also, the demand for apples is on the rise, and growers are planting high-density varieties so they can plant many more trees per acre of land. Commercial nurseries are now struggling to keep pace with the demand for apple trees. Nursery owners may decide that planting for small specialty crops like cherries just isn’t worth it any more.

Now back to trouble sleeping: if you find that tart cherry juice helps you sleep, you’d be wise to stock up on it now.