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.

Transitioning to Menopause? Don’t Give Up on Sound Sleep

I often hear sleep complaints from women approaching menopause. Hot flashes and mood swings are other common complaints. What can be done to improve sleep and reduce perimenopausal symptoms?

The key, say authors of a review paper published this year, is to use a variety of approaches based on individual women’s symptoms, history and needs.

Insomnia and hot flashes can be relieved with multi-pronged treatmentI often hear sleep complaints from women approaching menopause. Hot flashes and mood swings are other common complaints. What can be done to improve sleep and reduce perimenopausal symptoms?

The key, say authors of a review paper published this year, is to use a variety of approaches based on individual women’s symptoms, history and needs.

Sleep Problems in the Menopausal Transition

The transition to menopause begins 4 to 6 years before menstruation stops (the median age for menopause is 51 years). It’s a time of fluctuating reproductive hormone levels. Not all women suffer ill effects during this period but many do.

Sleep problems are one of the most common complaints, reported by up to 56% of women approaching menopause, say authors of the review, published in the journal Nature and Science of Sleep. In turn, trouble sleeping often compromises midlife women’s quality of life, mood and productivity.

There’s an uptick in sleep-disordered breathing (sleep apnea) among women transitioning to menopause. There’s also an uptick in insomnia. A study involving 982 perimenopausal women interviewed by phone found that 26% had symptoms qualifying them for a diagnosis of insomnia disorder as medically defined.

Not Just in Our Heads

Fluctuating levels of hormones—follicle-stimulating hormone, estradiol (an estrogen) and progesterone—likely play a role in insomnia that occurs during the menopausal transition. Hot flashes, too, which typically emerge as estrogen levels decline, are associated with poorer reported sleep quality and chronic insomnia.

As for objective evidence of menopausal sleep problems, results of population studies of midlife women involving polysomnography (PSG) are inconsistent. But in a recent study published in Psychoneuroendocrinology, investigators found “stark differences in PSG measures in women with, relative to women without, insomnia disorder developed in the menopausal transition.”

Women who developed insomnia during the menopausal transition

  • had poorer sleep efficiency
  • experienced more wakefulness after sleep onset
  • had shorter total sleep time, with 50% sleeping less than 6 hours
  • were more likely to have hot flashes, which predicted their number of awakenings per hour of sleep.

A Role for Depression and Stress

Symptoms of depression typically increase during the menopausal transition. Depression and insomnia are closely linked, with depression sometimes preceding insomnia and insomnia sometimes leading to depression. The results of one interesting study suggest that trouble falling asleep at the beginning of the night is associated with anxiety while nonrestorative sleep is linked to depression.

Chronic exposure to stress could be another factor in midlife women’s greater susceptibility to insomnia. And during the transition to menopause, traits associated with insomnia—increased tendency toward rumination, anxiety, generalized hyperarousal, stress reactivity, and neuroticism—are similar to tendencies predictive of hot flashes and other perimenopausal symptoms.

Treatments for Insomnia in the Menopausal Transition

Since insomnia in the menopausal transition is likely due to many factors, it’s challenging to treat. The reviewers recommend “flexible and individualized” treatments for insomnia depending on each woman’s current symptoms and history.

Hormone Therapy

Hormone therapy generally improves sleep quality in women who experience hot flashes during the transition. It may be a good option if, based on a woman’s history and health concerns, the overall potential benefits outweigh the risks. The reviewers note that abrupt discontinuation of hormone therapy is associated with hot flash relapse, which could in turn lead to insomnia.

Non-Hormonal Pharmacological Therapies

Sleeping pills, which are generally prescribed for short-term or intermittent use, are not a front-line treatment for insomnia in perimenopausal women. Taken nightly over time, many sleeping pills degrade sleep quality and have other negative effects. Following are the medications the reviewers suggest considering for perimenopausal women with insomnia and hot flashes:

  • Low-dose selective serotonin reuptake inhibitors—such as citalopram (Celexa) and escitalopram (Lexapro)—and low-dose serotonin norepinephrine reuptake inhibitors—such as duloxetine (Cymbalta) and venlafaxine (Effexor XR). Note that discontinuation of SSRIs is associated with hot flash relapse, which could lead to insomnia.
  • Gabapentin, shown to improve sleep quality in perimenopausal women with hot flashes and insomnia.
Non-Pharmacological Therapies
  • Cognitive behavioral therapy for insomnia (CBT-I) is the overall gold standard in drug-free treatments for insomnia. In a randomized clinical trial recently conducted on peri- and postmenopausal women experiencing at least 2 hot flashes daily, women who underwent CBT-I “had significantly greater reduction in insomnia symptoms and greater improvements in self-reported sleep quality” compared with controls. The improvements were maintained at 6 months after treatment.
  • Soy isoflavones—phytoestrogens found mainly in legumes and beans—have been shown in randomized controlled trials to reduce menopausal symptoms, including self-reported sleep disturbance. They’re available as dietary supplements.
  • High-intensity exercise and yoga are reported by the reviewers to be modestly beneficial in reducing menopausal symptoms and improving sleep.

Because many factors can combine to disrupt sleep in the period leading up to menopause—sleep disorders, mood disorders, medical conditions, and life stressors—no one-size-fits-all treatment will improve sleep and minimize menopausal symptoms. Instead, the reviewers recommend a multi-pronged approach to treatment based on individual women’s needs.

Anniversary Book Giveaway Marks Change in Blog

It’s time for a couple of announcements: The Savvy Insomniac came out four years ago today and we’re giving away 10 copies of the book to mark the occasion. Read on to find out how to get one yourself!

Announcement No. 2: I’ve been blogging weekly about insomnia for five years and now, starting in October, I’ll be posting once a month. I’m as committed as ever to offering news and perspective on issues related to sleep and insomnia. But other projects are calling and taking more time.

Here are the giveaway details. After that, a summary of popular blog topics you’ll hear more about in the future.

Still blogging about insomnia—now, once a month

It’s time for a couple of announcements: The Savvy Insomniac came out four years ago today and we’re giving away 10 copies of the book to mark the occasion. Read on to find out how to get one yourself!

Announcement No. 2: I’ve been blogging weekly about insomnia for five years and now, starting in October, I’ll be posting once a month. I’m as committed as ever to offering news and perspective on issues related to sleep and insomnia. But other projects are calling and taking more time.

Here are the giveaway details. After that, a summary of popular blog topics you’ll hear more about in the future.

Book Giveaway

First, heartfelt thanks to those of you who follow my blog. It’s one thing to visit a website now and then but quite another to sign up for news from a blogger who posts a 600- to 800-word story every week! Your interest in insomnia and insomnia treatments must be as deep and personal as mine.

For all the blogging I’ve done about sleep and insomnia, though, The Savvy Insomniac is the best and most comprehensive writing I’ve done on the subject. Anyone living in the US who hasn’t got a copy and wants one can use the contact form to let me know. The first 10 people who contact me with a question about sleep or insomnia (something you wonder about but haven’t found much information about) will get a copy of The Savvy Insomniac free of charge.

Don’t forget to include your mailing address. Overseas shipping rates are so exorbitant that I can’t ship books abroad. But inexpensive e-books continue to be available through Amazon and other online booksellers.

Here, now, are the blog topics most popular with Savvy Insomniac readers. Count on hearing more about them in the months ahead.

Insomnia Relief in the Form of a Pill

Sleeping pills don’t get great press these days, but they have great interest for Savvy Insomniac readers. Posts about Belsomra, the newest sleeping pill approved for the treatment of insomnia, consistently get the most views. Belsomra acts as a sedative by blocking transmission of orexin, a neurochemical that promotes arousal. Other orexin-blocking sleeping pills are in the works. I’ll write about them if and when they’re approved by the FDA.

Posts about sedating antidepressants are also popular. Since many sleeping pills have undesirable side effects, persistent insomnia is sometimes treated with low doses of a sedating antidepressant. Doxepin has been approved as Silenor for treatment of sleep maintenance insomnia. The others (trazodone, mirtazapine, amitriptyline) have not been sanctioned by the FDA as effective for insomnia. They do, however, have sedative properties.

Melatonin supplements are also of high interest to readers, especially in timed-release formulations. But melatonin is not a sleeping pill. Its usefulness lies in its ability to shift the timing of sleep. Melatonin is sometimes recommended to night owls whose daytime schedules make it necessary to go to sleep earlier than they would following their natural inclinations. It also helps lessen jet lag.

Insomnia: What’s Your Flavor?

Posts on the different types of insomnia are the next most visited category. Since the underlying causes of insomnia disorder remain unknown, insomnia is usually classified based on the symptoms people report.

Psychophysiologic (or psychophysiological) insomnia is the most common insomnia diagnosis given to those of us who report trouble sleeping at night and daytime impairments. Symptoms are both physiological (bodily tension and warmth, for example) and psychological (anxiety about sleep). Cognitive behavioral therapy (CBT) is now the first-line treatment for psychophysiologic insomnia.

A diagnosis of paradoxical insomnia may be made following a sleep study showing a large discrepancy between how much time a person reports sleeping and how much sleep is recorded on the polysomnogram (the test in the sleep lab). Treatment options vary and there’s no clear consensus on which works best.

Sleep Restriction for Insomnia Relief

Sleep restriction therapy comes in for a close third topic of interest to Savvy Insomniac readers. Offered as part of CBT-I or as a standalone therapy, sleep restriction has been found in research to improve several aspects of sleep.

Its appeal to readers of this blog may have to do with the sheer number of posts I’ve written on the topic (10) and the fact that it worked so well for me. Combined with daily exercise, sleep restriction helped me regularize my sleep and overcome my sleep anxiety. Invaluable gains, to me.

Seasonal Insomnia

Insomnia that varies seasonally is another topic that draws lots of readers. Environmental factors that occur in the spring and summer—too much light and too much heat—can easily interfere with falling and staying asleep.

Insomnia that starts in the fall and continues through the winter may be driven by other environmental factors. Lack of sunlight or other bright light is usually the culprit. Lack of vitamin D may be another factor. Expect to see an update on this topic coming fairly soon.

Don’t see a topic that interests you here? Use the contact form to ask a question about a topic that does interest you, and receive a free copy of The Savvy Insomniac.

And here’s a last request: please like and share blog posts you feel are helpful on Facebook, Twitter, and other social media. This will help The Savvy Insomniac blog remain discoverable to other insomnia sufferers looking for a better night’s rest.

Lifelong Insomnia? Don’t Give Up on It Yet

Have you had insomnia all your life? Have your parents said you were a poor sleeper even as a baby?

Trouble sleeping that starts early in life is called idiopathic insomnia. If insomnia is still the black box of sleep disorders, then idiopathic insomnia is the little black box inside the black box.

Here’s what is known about the disorder and options for management.

Lifelong insomnia can be treated by sleep specialist or therapistHave you had insomnia all your life? Have your parents said you were a poor sleeper even as a baby?

Trouble sleeping that starts early in life is called idiopathic insomnia. If insomnia is still the black box of sleep disorders, then idiopathic insomnia is the little black box inside the black box.

Here’s what is known about the disorder and options for management.

What Is Idiopathic Insomnia?

Idiopathic insomnia begins in childhood, sometimes at or soon after birth. Trouble falling or staying asleep or reduced sleep duration is pretty much a nightly affair regardless of situational changes. The disorder is uncommon, affecting less than 1% of the population.

There is no identifiable cause. The presumption is that idiopathic insomnia is driven mainly by biological factors, and at least some of them are probably inherited. Abnormalities in the circadian system or the homeostatic process may be involved and/or there may be a problem in the circuitry controlling sleep and waking in the brain.

A Chronic Sleep Disorder, but How Well Defined?

Idiopathic insomnia is a chronic sleep disorder with familiar insomnia symptoms:

  • Trouble falling or staying asleep, or sleeping long enough, for more than 3 months despite adequate sleep opportunity
  • Daytime distress and impairment, including reduced stamina, low mood, and trouble thinking and learning

Research on the defining features of idiopathic insomnia is mixed. On one hand are a few studies showing significant differences between people with idiopathic insomnia (IdI) and those with psychophysiological insomnia (PI), the garden-variety insomnia that typically develops later in adolescence or adulthood. PI is often triggered by a stressful event; situational factors do not figure in IdI. PI is said to persist mainly due to psychological and behavioral factors that develop in response to poor sleep: conditioned arousal in bed, poor sleep hygiene (going to bed early to catch up on sleep, for example), and anxiety about sleep. Psychological factors are less typical in IdI.

On the other hand is research showing no major differences between PI and IdI when assessed by polysomnography (the overnight test in the sleep lab) or by self-report of psychological symptoms. Research suggests that arousal levels are higher among people with IdI than in people with other kinds of insomnia, though, leading some sleep experts to speculate that IdI is simply a more severe manifestation of PI.

What Can Be Done?

Without scientific certainty about the causes of IdI or whether the disorder is distinct from other kinds of insomnia, IdI is best treated on a case-by-case basis by a sleep specialist. Following are options for treatment.

Especially if a person with IdI has misconceptions and/or anxiety about sleep,

  • Cognitive behavioral therapy for insomnia (CBT-I) may help. CBT-I typically consists of two behavioral components—stimulus control therapy and sleep restriction therapy—and a cognitive component designed to decrease psychological barriers to sleep. Sometimes just changing your attitude about sleep can bring about demonstrable sleep improvements.
  • Acceptance and commitment therapy (ACT) may help. ACT focuses on building mindfulness skills so that, rather than trying to suppress, manage, and control emotional experiences, people develop psychological flexibility and learn to behave in ways that reflect their values and increase well-being. This approach, too, can change the way you feel about sleep and in the process improve your sleep.

If round-the-clock hyperarousal is driving IdI, then therapies designed to decrease arousal may help.

  • Regular, moderate-to-vigorous exercise—activities such as aerobics, calisthenics, biking, running, and weight-lifting—has been shown in recent studies to increase total sleep time and decrease levels of cortisol (a stress hormone).
  • Yoga, too, has been shown to decrease feelings of arousal and promote stress tolerance.

Medication for Idiopathic Insomnia

The issue of sleeping pills for chronic insomnia is increasingly fraught. Many drugs approved for the treatment of insomnia, taken nightly over time, may degrade sleep quality and result in alarming side effects, especially in older adults.

That said, while the medication prescribed for IDI is usually a benzodiazepine or a Z-drug such as zolpidem or eszopiclone, a second pharmacological approach, according to a paper by Michael Perlis and Philip Gehrman, involves use of a melatonin agonist such as ramelteon (Rozerem). No studies of the effects of this sleeping pill on the sleep of adults with IdI have been conducted. But in two studies of children aged 6 to 12 years with chronic idiopathic childhood sleep-onset insomnia, melatonin put them to sleep significantly sooner—by 1 hour.

If you’re contemplating managing lifelong insomnia with drugs, get some professional advice. This is one place where you really need the help of a specialist knowledgeable in the medical treatment of chronic insomnia.

At what age did your trouble sleeping start? What kinds of treatments—if any—have helped?

Herbals for Insomnia? Now You Can Test Them at Home

Herbal remedies for insomnia are abundant online—valerian, hops, and chamomile, among the most common. Tested against placebo, none has been found to be definitively effective for insomnia. Yet some medicinal herbs have a long history as traditional calming, sleep-promoting agents. Might one work for you?

Researchers at Massachusetts General Hospital and Harvard Medical School have proposed a method you can use yourself to test herbal remedies via personalized therapeutic trials. Here’s more about herbals and how the trials work:

Insomnia may respond to treatment with herbal supplements and tincturesHerbal remedies for insomnia are abundant online—valerian, hops, and chamomile, among the most common. Tested against placebo, none has been found to be definitively effective for insomnia. Yet some medicinal herbs have a long history as traditional calming, sleep-promoting agents. Might one work for you?

Researchers at Massachusetts General Hospital and Harvard Medical School have proposed a method you can use yourself to test herbal remedies via personalized therapeutic trials. Here’s more about herbals and how the trials work:

Why Herbals for Sleep?

Interest in herbal and other alternative treatments for insomnia seems to be on the rise. About 5% of the participants in a national survey reported use of complementary and alternative medicine (CAM) for insomnia in 2002. A recent analysis of the same national survey conducted in 2007 found that almost 50% of participants with insomnia symptoms used some form of CAM therapy.

Some insomniacs see alternative medicines as less risky than prescription sleeping pills, with fewer potentially harmful side effects. Because they are “natural,” they’re viewed as more appropriate for long-term use than many sleeping pills, which, if used nightly, tend eventually to degrade sleep quality.

Scant Testing, Mixed Results

Most herbal remedies for sleep have not undergone as much testing as prescription sleeping pills (one reason may be that there’s relatively little money to be made on them). But as with sleeping pills, tests that have been conducted on herbals often show subjective sleep improvements that exceed objective measures.

The perception that herbal supplements improve sleep could be due to a placebo effect. Or, say the Massachusetts researchers, it could be attributable to basic differences among trial participants, including different insomnia symptoms. It could be that, just as a particular sleeping pill works for some insomniacs and not others, a particular herb may relieve insomnia in some people and not others.

Herbals That May Relieve Insomnia

Since the overall efficacy of herbal preparations for insomnia is still unknown and may differ from person to person, the researchers opted to consult six authoritative resources in their search for herbal and supplement remedies of potential relevance for insomnia, including reference books such as the Physician’s Desk Reference for Herbal Medicines (PDR) and online sources such as Medline Plus. In all, they came up with a list of over 70 herbal agents of possible benefit to sleep.

These 15 medicinal herbs were listed by 4 or more resources as a remedy for insomnia or another condition indirectly related to sleep, such as anxiety or nervousness:

  1. Ashwagandha
  2. Bitter Orange (Neroli)
  3. Catnip (Nepeta)
  4. Chamomile (German)
  5. Hops
  6. Kava
  7. Lavender (English)
  8. Lemon Balm
  9. Linden
  10. Nutmeg (and Mace)
  11. Oats (Avena sativa)
  12. Passion Flower
  13. Schisandra (Wu-Wei-Zi)
  14. St. John’s Wort
  15. Valerian

Safety of Herbal Supplements

Natural substances are not necessarily safe for unrestricted use. The PDR for Herbal Medicines cautions against using several during pregnancy. Some herbs may be harmful to the liver. And, as herbal supplements are unregulated in the United States, the contents of a supplement do not necessarily reflect what appears on the label. In fact, a majority of herbal remedies evaluated in a recent study had contamination, substitution, or use of fillers not listed on the label.

For safety concerns associated with herbs used for insomnia, see these sources:

Find Out If a Sedating Herb Works for You

Let’s say you’re a sleep maintenance insomniac, awakening at least twice a night to feelings of anxiety. You’ve heard that passion flower is good for sleep and anxiety, and you’d like to try it to see if it cuts down on your nighttime wake-ups. But how long should you try it? Two nights, three nights or more?

Many insomniacs experience quite a bit of night-to-night variability in their sleep. When you’re stressed out you might sleep poorly for 4 or 5 nights in a row before you get a decent night’s sleep. If you tried taking a passion flower supplement for just 2 or 3 nights during a time of stress, the results you obtained wouldn’t be reliable. You might obtain a different result if you tested the passion flower during a 3-day period when your life was moving along on an even keel.

I’ll skip the authors’ discussion of statistical power and cut to the chase: you need to test a substance for 10 nights in a row to have reasonable certainty that the result you obtain is repeatable and you’ve got enough data to answer the question of whether passion flower improves your sleep.

Self-Testing Flow Chart

Follow these 5 steps to determine whether an herbal insomnia remedy works for you:

  1. Simplify sleep. For you, does “good sleep” mean falling asleep sooner, sleeping longer, waking up feeling more rested, or waking up less at night? Choose the one thing that for you would most improve your sleep.
  2. Set a goal. Choose your target “good night” value and a percentage of nights for which this target value must occur. Let’s say you decide that a good night is a night when you awaken just 1 time or less (and on a bad night you awaken 2 times or more). Let’s say you set your goal at awakening 1 time or less on at least 70% (7 out of 10) of the nights.
  3. Choose a therapy. Try one intervention at a time. Starting a passion flower supplement and a yoga class at the same time will muddle the results.
  4. Do the 10-day test. Every day, record good nights and bad nights in a diary.
  5. Calculate the outcome. Did you achieve your goal? If so, you can conclude that passion flower improves your sleep. If you didn’t achieve your goal, clearly the passion flower did not work. Choose another therapy, starting the process at #3. If your results are borderline, continue testing for another 10 days. Then recalculate to ascertain whether you’ve met your goal of awakening 1 time or less on 70% of all 20 nights.

Insomniacs are big experimenters, I learned as I was conducting research for my book, The Savvy Insomniac. Several expressed interest in herbal and other alternative treatments. If you’re going to experiment, you need a systematic way to assess whether the remedy you’re trying improves your sleep or not. These Massachusetts researchers have given us a goal-oriented algorithm for doing exactly that.

Use OTC Sleep Aids With Caution

The sleeping pill of choice for many Americans with insomnia can be purchased over the counter at drug and grocery stores. But a new study shows that many older adults who use OTC sleep aids know little about them and may be using them in ways that do more harm than good.

Sleeping pill users should read the label of OTC sleep medicationsIt annoys me when people dismiss sleeping pills as categorically harmful. Yes, they can be used inappropriately and it’s important to be informed about their downsides. But the existence of downsides doesn’t necessarily mean the risks associated with using them outweigh the benefits.

The sleeping pill of choice for many Americans with insomnia can be purchased over the counter at drug and grocery stores. But a new study shows that many older adults who use OTC sleep aids know little about them and may be using them in ways that do more harm than good.

Older Americans Use Them and Like Them

Participants in the new study were adults in the United States aged 60 and older who were managing their sleep problems with nonprescription sleep aids. University of Pittsburgh investigators interviewed 116 by telephone and found that well over half were satisfied with their medication and felt it improved their sleep.

Asked about her satisfaction with one such drug, an interviewee replied that she was “pretty satisfied. It does help me fall asleep and stay asleep, and go back to sleep when I invariably get up once or twice a night.”

“There is a dramatic difference when I use it versus when I don’t,” another explained.

This jibes with the results of other, quantitative research. The prevalence of insomnia and other sleep problems among older adults is high and OTC sleep aids are widely available. About 17% of older adults in the United States turn for relief to antihistamine-containing sleep aids like Unisom and Simply Sleep.

How OTC Sleep Aids Work

Diphenhydramine and doxylamine are the active ingredients in antihistamine sleep aids. They block the action of histamine neurons, which are generally active when we’re awake and inactive when we’re asleep.

“Marked drowsiness may occur,” is the type of warning that usually appears on the label. This propensity to cause sedation is likely why, despite few controlled trials supporting their efficacy for insomnia, these drugs are seen as effective by many older adults. The trials that have been conducted suggest these antihistamine sleep aids may have more to offer sleep maintenance insomniacs than people who need help falling asleep at the beginning of the night.

Side Effects of OTC Sleep Aids

But like most prescription medications, OTC sleep aids are not intended for nightly or long-term use. Continuous use has been found to lead to the development of tolerance, tempting users to take more of the drug to get the same sedative effect. Yet in the Pittsburgh study, nearly half of the participants reported using OTC sleep meds daily or very often. Over half reported using them for more than a year.

Fewer than a quarter of the study participants had studied the label on their medication to find out about the recommended dosage or about warnings and possible side effects.

“I never really paid any attention to the directions,” an interviewee said. “I take a couple before I go to bed, about twenty minutes before I go to sleep, I go upstairs and go to bed. That’s it.”

Common side effects to be aware of are morning grogginess (our bodies process drugs more slowly as we age) and blurred vision, constipation, and trouble urinating (for more on this, see my post on OTC sleep aids and anticholinergic effects).

Drug-Drug Interactions

Possible drug-drug interactions is another factor to take into account, given that almost 40% of older Americans are taking five or more prescription medications. Studies have shown that diphenhydramine (the main ingredient in many OTC sleep aids, including Benadryl, Sominex, Nytol, ZzzQuil, and Simply Sleep) interferes with the body’s metabolizing of at least three commonly prescribed drugs:

  1. tamoxifen, an anti-estrogen drug used to treat breast cancer and lower breast cancer risk
  2. metoprolol (Lopressor), a beta blocker used to treat high blood pressure and heart problems
  3. venlafaxine (Effexor), a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) used to treat depression

Reducing the effectiveness of a drug taken to manage a serious health condition isn’t something most of us would want to do. But information about all possible drug-drug interactions isn’t necessarily listed on the label of OTC sleep aids.

Americans seem to have the attitude that OTC meds are harmless—but that isn’t necessarily true. If you’re going to use an OTC sleeping pill, read the label for information about the proper dosage and potential side effects. Take concerns about possible drug-drug interactions to your doctor or pharmacist.

Sleeping Pills: New Prescribing Guidelines

Let’s say you go to the doctor hoping to get a prescription for sleeping pills to relieve your insomnia. You’ve been through cognitive behavioral therapy and it has helped. But there are nights when you’re wound up so tightly that nothing—push-ups, meditation, a hot bath—will calm you down enough so you can get a decent night’s sleep. What then?

The American Academy of Sleep Medicine recently released a clinical practice guideline for the medical treatment of chronic insomnia in adults. Here’s what the academy now recommends.

New guideline for sleeping pills may change doctors' prescribing habitsLet’s say you go to the doctor hoping to get a prescription for sleeping pills to relieve your insomnia. You’ve been through cognitive behavioral therapy and it has helped. But there are nights when you’re wound up so tightly that nothing—push-ups, meditation, a hot bath—will calm you down enough so you can get a decent night’s sleep. What then?

The American Academy of Sleep Medicine recently released a clinical practice guideline for the medical treatment of chronic insomnia in adults. Here’s what the academy now recommends.

Why the Need for a Clinical Practice Guideline?

Most experts in sleep medicine are well acquainted with the literature on sleeping pills and know how to diagnose and treat insomnia. When medication for insomnia is warranted, they know the best drug to prescribe based on your symptoms and medical history.

But most people with sleep complaints take them first to primary care providers. And when it comes to prescribing sleeping pills, not all doctors are on the same page. In fact, a new study from Harvard Medical School shows that, rather than prescribing based on individual patients’ symptoms and history, many doctors find one or two sleep medications they’re comfortable with and prescribe the same drug or drugs again and again.

The new clinical practice guideline contains recommendations that are evidence based. It has the potential to change physicians’ prescribing habits and thus to affect people with insomnia who use sleeping pills, now and in the future.

The Guidelines Are Based on Weak Evidence

The four sleep experts who created the guideline first conducted a literature review. They concluded that no sleeping pill or sleep aid on the market today has been tested in multiple clinical trials and found to be extremely effective and carry very few risks. So the evidence base for their recommendations is, they note, “weak.”

This doesn’t mean that a given medication would not be appropriate and effective for a particular individual with insomnia. It just means as a general treatment for everyone with chronic insomnia, no sleeping pill is backed up strongly by the evidence.

These Sleeping Pills Got a Thumbs-Up

Perhaps predictably, the medications judged to be appropriate—based on the quality of evidence, the balance of benefits and harms, and patient values and preferences—are medications approved by the FDA for the treatment of insomnia. The guideline does not suggest that one drug is better than another since so few studies comparing the efficacy of two or more sleeping pills have been conducted. So the medications listed here are in no particular order:

MEDICATION

SLEEP ONSET INSOMNIA

SLEEP MAINTENANCE INSOMNIA

suvorexant (Belsomra)  X
eszopiclone (Lunesta) X  X
zaleplon (Sonata) X
zolpidem (Ambien) X
triazolam (Halcion) X
temazepam (Restoril) X X
ramelteon (Rozerem) X
doxepin (Silenor) X

These Sleep Aids Were Not Recommended

The following medications and supplements are sometimes prescribed and used for chronic insomnia. Depending on an individual’s symptoms and history, they may help. But the published data on these substances is insufficient in quantity and/or quality to warrant a recommendation for general use as a treatment for chronic insomnia.

  • trazodone (a sedating antidepressant)
  • tiagabine (an anticonvulsant approved for the treatment of epilepsy and used off-label to treat anxiety and panic disorders)
  • diphenhydramine (the antihistamine found in most over-the-counter sleep aids, including ZzzQuil, Sominex, and Tylenol PM)
  • tryptophan (a supplement containing an amino acid found in milk and other sources of dietary protein)
  • melatonin (a supplement which is bio-identical to a hormone produced in the body, useful for jet lag and delayed sleep phase disorder)
  • valerian (a plant-based supplement)

If you’ve used any of these medications or supplements, how effective were they, and did you experience any side effects?

A Beta Blocker for Stress-Related Insomnia

Is your insomnia linked to stress? When you go to bed at night, are you suddenly aware of your heart beat, muscle tension, and bodily warmth?

A drug now in the pipeline may one day be available to treat stress-related insomnia—if it measures up to its developers’ expectations.

Stress-related insomnia may respond to treatment with a beta blockerIs your insomnia linked to stress? When you go to bed at night, are you suddenly aware of your heart beat, muscle tension, and bodily warmth?

A drug now in the pipeline may one day be available to treat stress-related insomnia—if it measures up to its developers’ expectations.

It’s Not a New Drug

New medications are expensive and time consuming to develop. So many drug companies are now bent on repurposing drugs whose side effects suggest other possible uses.

In the world of sleeping pills this is déjà vu. Over-the-counter sleep aids like ZzzQuil and Sominex, whose active ingredient is diphenhydramine, got their start with the first-generation antihistamines that came on the scene in the late 1940s and 1950s. These antihistamines were originally sold to combat allergies and relieve cold symptoms. But none were free of the side effect of drowsiness. So manufacturers like Rexall and J.B. Williams decided to cash in on that property and market them as sleeping pills instead.

Drowsiness is also a side effect of some antidepressant medications. Doxepin, an old tricylic antidepressant, is one such drug. It achieves its sedating effect by blocking transmission of histamine—even at very low doses. Somaxon Pharmaceuticals saw a money-making opportunity here. Silenor, a drug the company “developed” for treatment of sleep maintenance insomnia and which came to market in 2010, is the equivalent of low-dose doxepin.

A Beta Blocker for Insomnia

Now a company called Blake Insomnia Therapeutics is developing an insomnia drug whose main ingredient is the beta blocker nebivolol. As a class, beta blockers are used to treat hypertension and cardiovascular conditions. They block the effects of the stress hormone epinephrine (Adrenalin). This causes blood vessels to expand, lowering blood pressure and heart rate.

“But wait a minute,” you may be thinking. “Aren’t beta blockers known to cause insomnia in some users?”

Yes. First- and second-generation beta blockers have been found to cause insomnia and nightmares in some users, as well as reductions in REM sleep. Beta blockers also block secretion of melatonin, a sleep-friendly hormone released at night.

Nebivolol, a third-generation beta blocker, is different, the research shows. It does not inhibit melatonin secretion. Nor, taken in the evening, does it cause morning drowsiness—a common shortcoming of many sleeping pills on the market today.

How It Could Affect Sleep

Chronic stress-related insomnia is fueled by several factors that feed one another. Some are psychological, such as rumination and anxiety about sleep. Others are physiological, affecting heart rate and skeletal muscles, among other things. Awareness of the physiological symptoms of arousal—such as an increased or erratic heart beat and muscle tension—tends to escalate anxiety, which in turn exacerbates the physiological symptoms, and on and on. Pretty soon you’re caught up in a vicious circle and unable to calm down.

A nebivolol compound would be expected to dial down the physiological symptoms associated with stress-related insomnia. Without the troublesome physiological symptoms, insomniacs wouldn’t experience so much anxiety about sleep, company CEO Birger Jan Olsen maintains. He contends that by removing many of the physiological and psychological symptoms fueling stress-related insomnia, the drug will improve sleep. (It did so for Olsen’s mother. Her intractable insomnia responded to treatment with nebivolol.)

Will the Drug Ever Come to Market, and When?

The good news here is that the new compound, called Zleepax, is made from substances that are generally recognized as safe in the United States and Europe. So the company can skip phase I testing altogether. If the drug is eventually approved by the FDA, its main selling point will be that unlike many insomnia medications—scheduled drugs associated with the risk of developing tolerance when used long term—Zleepax does not cause morning drowsiness or carry the same long-term risks.

Phase II testing is set to begin this year. If all goes well, Phase III testing will follow. The company is projecting a product launch in 2022.

But the road to FDA approval is fraught with challenges. The company is still trying to raise money to fund the necessary trials. The drug’s performance could be lukewarm in large-scale tests. Undesirable side effects could be discovered along the way.

Even so, the drug sounds promising. Too bad the development process cannot be speeded up.

Does a drug like this sound like it might be helpful to you?