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.

Belsomra: Weighing Benefits and Risks

Belsomra, Merck’s new sleeping pill, is now the hottest topic on this blog. Insomnia sufferers who write in with comments are wondering about dosage, effectiveness, side effects, and how it compares with other sleeping pills.

Reviews of Belsomra, or suvorexant, have been lukewarm so far. Since I haven’t tried it myself, I can’t weigh in based on personal experience. But my search for information turned up more than I shared in my blog last August. Here’s a bit of context and more details.

insomnia sufferers should weigh benefits & risks of new sleeping pillBelsomra, Merck’s new sleeping pill, is now the hottest topic on this blog. Insomnia sufferers who write in with comments are wondering about dosage, effectiveness, side effects, and how it compares with other sleeping pills.

Reviews of Belsomra, or suvorexant, have been lukewarm so far. Since I haven’t tried it myself, I can’t weigh in based on personal experience. But my search for information turned up more than I shared in my blog last August. Here’s a bit of context and more details.

How to Put the Brain to Sleep

There are two ways to induce sleep chemically: by (1) facilitating the action of neurons that promote sleep and (2) deactivating neurons associated with arousal. Z-drugs like zolpidem (Ambien) and eszopiclone (Lunesta) do the former. They enhance the ability of GABA neurons to shut the brain down.

Belsomra, on the other hand, works by disabling the orexin neurons that fire continuously when we’re awake. These orexin neurons—70,000 in all–reside in a part of the brain called the hypothalamus. They’re connected to GABA neurons there, and when the orexin neurons are firing, they hold GABA neurons in check.

Mice that lack orexin neurons are constantly falling asleep. In mice that have orexin neurons, temporarily disabling the neurons also puts the mice to sleep. Blocking the action of the orexins in humans should have a similar effect.

Why Shouldn’t We Stick with Drugs That Act on GABA?

The problem with these drugs is that in some users they have negative side effects: sleep walking, sleep eating, and sleep driving, not to mention interfering with memory formation and possibly increasing mortality. For several years the z-drugs were touted as safe for long-term use, but post-marketing tests have given rise to skepticism among some healthcare providers.

Besides, although sleep scientists are still unclear about the causes of insomnia, the prevailing theory is not that insomnia is the result of a flawed sleep system but rather that it stems from excessive arousal, which is conditioned and/or genetically predisposed. The word often used to describe our predicament is hyperarousal. So it makes sense drug developers are working on insomnia drugs that will tamp the arousal down.

Safety and Efficacy of Belsomra

The safety and efficacy of the drug apparently depend on the dose. The FDA approved Belsomra in doses of 5, 10, 15, and 20 mg based on the results of 3 double-blind, placebo-controlled trials that showed it to be better than placebo at putting subjects to sleep and keeping them asleep.

Merck also conducted a one-year safety study in which investigators also looked at the efficacy of 30 and 40 mg of the drug. By the end of the first month, patients taking suvorexant were falling asleep 10 minutes faster than patients taking a placebo and sleeping about 23 minutes longer.

But the main purpose of this study was to assess the drug’s safety. In this respect, suvorexant performed well enough. Subjects who took suvorexant maintained their sleep improvements throughout the year. When they stopped taking the drug at the end of the study, they experienced no more rebound insomnia or withdrawal symptoms than the placebo group. This suggests the drug’s potential to foster the build-up of tolerance and dependency is low.

The one prominent safety issue that did come up was daytime grogginess, unsurprising in a drug whose half-life is about 12 hours. Of the patients on Belsomra, 13 percent experienced next-day sleepiness, sometimes severe, compared to 3 percent on placebo. In studies where patients were taking lower doses of Belsomra—15 and 20 mg—fewer patients experienced next-day sleepiness (7 percent vs. 3 percent on placebo).

The tradeoff, though, was reduced efficacy, especially in doses under 20 mg. Subjects who took a 10-mg dose did not get to sleep significantly sooner than patients on placebo (although they did sleep about 22 minutes longer). So it looks like business as usual here: higher doses are more efficacious but they may also leave you feeling groggy and impair your driving ability the next day.

How Does Belsomra Compare with Other Sleeping Pills?

Merck did not conduct any toe-to-toe comparison studies. The FDA does not require that new drugs be tested against existing drugs. Comparison studies, if they’re done at all, are typically conducted after a new drug comes out.

But results of a Phase-2 study showed that in healthy subjects, suvorexant altered the overall electrical activity in the brain less than 3 other medications—gaboxadol, zolpidem, and trazodone–used for sleep. These findings, say investigators, suggest that drugs like suvorexant “might lead to improvements in sleep without major changes in the patient’s neurophysiology as assessed by electroencephalography.”

Orexin Drugs Coming Our Way in the Future

Our bodies actually produce 2 different orexin neuropeptides and have 2 different orexin receptors. Belsomra is a “dual orexin receptor antagonist,” or DORA. It promotes sleep by blocking both orexins from binding to their receptors.

In the laboratory, writes Cormac Sheridan in the October 2014 issue of Nature Biotechnology, Belsomra over time shows a greater binding affinity for the orexin-1 receptor. Yet animal knockout studies suggest that of the 2 receptors, the orexin-2 receptor may actually be more important to sleep regulation. So the activity profile of Belsomra may not be ideal.

At least 2 drug companies–GlaxoSmithKline and Minerva Neurosciences—have orexin receptor antagonists in the works. Drugs that more strongly target the orexin-2 receptors may prove to be more effective as hypnotics than Belsomra. The race is on to see.

If you have tried Belsomra, what do you think of it?

 

Will Ambien Get a Second Life?

Sleeping pills usually tarnish with age. Zolpidem (Ambien), approved for the treatment of insomnia, is no different.

But a new study from Stanford suggests that low doses of zolpidem may help people recover more quickly from stroke. Here’s the gist of that study, published on December 18 in Brain, and what post-marketing studies tell us about zolpidem used for insomnia.

ambien, despite many adverse effects, may get a 2nd lifeSleeping pills usually tarnish with age. Consider zolpidem (Ambien), approved for the treatment of insomnia.

Once touted as superior to other sleeping pills, zolpidem today is known to have factored in thousands of accidents and emergency department visits. In January 2013 the Food and Drug Administration cut the recommended dosage for women in half, and experts are urging physicians to cut back on prescriptions for adults over 65.

But a new study from Stanford suggests that low doses of zolpidem may help people recover more quickly from stroke. Here’s the gist of that study, published on December 18 in Brain, and what post-marketing studies tell us about zolpidem used for insomnia.

Effects of Zolpidem on the Brain

Zolpidem, like most other sleeping pills, acts on the GABA system. It facilitates the transmission of GABA, the main neurotransmitter responsible for calming the brain. GABA-producing neurons are distributed throughout the brain, and when they start firing, they inhibit the firing of adjacent neurons that are active when we’re awake. Zolpidem speeds this process up, shutting the brain down quickly and putting us to sleep.

But this ability of GABA neurons to prevent adjacent neurons from firing also plays a role in brain development. In fact, this phasic inhibition enables the organization and reorganization of the neuronal networks we humans need to process different kinds of information. So researchers in recent years have sought to find out if the GABA “signaling” that occurs during normal brain development also occurs as the brain regains function following a stroke.

What They Knew and How They Conducted the Study

The Stanford investigators already knew that during the first few hours following a stroke, enhancing phasic GABA was neuroprotective: other research had shown that it reduced the death of nerve cells. But no prior research had established whether phasic GABA was similarly beneficial during stroke recovery—during the days, weeks, and months when the cortex is endeavoring to rewire itself and regain functionality.

The experiment, which they conducted on mice, involved several steps. Among them were (a) anesthetizing the mice, (b) inducing the stroke, (c) observing what then occurred in the brain using an advanced neuroimaging technique called array tomography, (d) administering low-dose zolpidem to some of the mice starting on Day 3 after the stroke, (e) observing as, during stroke recovery, the mice underwent tests of their fine and gross motor skills, and (f) comparing the recovery of mice on zolpidem to the recovery of the mice that did not receive the zolpidem.

What They Found Out

  • After the stroke, the regaining of motor skills was accompanied by increased phasic GABA signaling in the mouse cortex.
  • The mice given low-dose zolpidem recovered their motor skills much faster than the control mice.

This preliminary study will need to be repeated before tests are conducted on humans. But if the findings hold up, zolpidem may one day be a first line of defense for people who have strokes.

Zolpidem for Insomnia

Zolpidem’s use as a sleeping pill has become controversial in recent years. The results of one study show that users are more prone to retain negative memories than nonusers. Post-marketing studies also suggest that older adults who use zolpidem are more likely than nonusers to experience falls and hip fractures. And preliminary evidence suggests that zolpidem may be associated with the development of dementia, cancer, glaucoma, pancreatitis, and epilepsy.

So if zolpidem is your hypnotic of choice, take care to use it only as directed and only if you need it.

If you use Ambien, have you experienced any negative effects related to the drug?

Will Ambien Go the Way of Halcion?

In the early 1990s, word was spreading that Halcion, a popular short-acting sleeping pill prescribed for insomnia, was a dangerous drug. Not only did it make users anxious, depressed, and suicidal.

It was also implicated in a series of murders. Sales of Halcion plunged. Today the drug is still on the market but is rarely prescribed.

Now zolpidem (Ambien) is receiving intensive post-marketing scrutiny, raising questions about the drug’s safety.

Ambien now is known to cause adverse effects and its use may decreaseIn the early 1990s, word was spreading that Halcion, a popular short-acting sleeping pill prescribed for the treatment of insomnia, was a dangerous drug. Not only did it make users anxious, depressed, and suicidal.

It was also implicated in a series of murders. (The murderers were absolved of their crimes based on the argument that Halcion rendered people incapable of understanding their actions). Sales of Halcion plunged. Today the drug is still on the market but is rarely prescribed.

Now zolpidem (Ambien) is receiving intensive post-marketing scrutiny, raising questions about the drug’s safety. In January 2013 the Food and Drug Administration lowered the recommended dose for women and older adults from 10 mg to 5 mg following reports of zolpidem-related car crashes and an analysis linking the drug to drowsiness in the morning. Studies and reports published in the past 2 years cast more doubt on the drug’s safety. So is zolpidem now set to go the way of Halcion?

A Popular Sleeping Pill

About 5 million Americans now use medications containing zolpidem (generic zolpidem, Ambien, Ambien CR, Intermezzo, Edluar, and Zolpimist), according to the Institute for Safe Medication Practices. Like several other sleeping pills, zolpidem acts on GABA-producing neurons, helping tranquilize the brain.

Benzodiazepine drugs like Halcion bind to several kinds of GABA receptor complexes and consequently produce a range of adverse effects. Zolpidem binds more selectively. Early tests showed that it facilitated sleep and produced fewer adverse effects.

So the FDA in 1992 approved zolpidem for “short-term treatment of insomnia characterized by difficulties with sleep initiation.” FDA approval of the extended-release version came in October 2005—notably without the short-term restriction. Zolpidem in its many formulations dominated the hypnotics market for years despite occasional reports of people sleepwalking, sleep eating, and sleep driving under its influence.

A Troubling CDC Report

People with zolpidem-related problems and injuries were also showing up in hospital emergency departments. The Centers for Disease Control and Prevention recently reported on a survey of psychiatric medications identified as the reason for emergency department visits.

The results were surprising: of all psychiatric medications prescribed, zolpidem ranked first in adverse drug event cases. About 11.5 percent of all emergency department visits among adults were attributable to zolpidem, as were 21 percent of the visits in adults 65 and older. Authors of the report estimated that zolpidem accounted for 10,212 annual visits to hospital emergency departments, 25 percent of which required hospital admission.

Regular Users at Risk

Two new cohort studies suggest that it’s the regular users of zolpidem who are prone to serious accidents:

  1. In a study in Mayo Clinic Proceedings (May 2014), Taiwanese investigators found that long-term zolpidem use significantly increased the risk of major injuries requiring hospitalization. Depending on the dosage, users young and old were 2 to nearly 5 times as susceptible as nonusers to head injuries and fractures.
  2. In a large study in the American Journal of Public Health (August 2015), University of Washington researchers used new prescription and collision records to determine the relationship between the use of sleeping pills and motor vehicle crashes. Regular users of zolpidem were over twice as likely to have crashes as nonusers.

Some Perspective on the Problem

Why is a medication approved as safe and effective by the FDA causing so many problems? The Institute for Safe Medication Practices analyzed a 2012 health care survey to find out if zolpidem was being prescribed and used in a manner consistent with safe use guidelines. Here’s a summary of the report, which appeared in the May 6, 2015, issue of QuarterWatch:

  • Zolpidem was originally approved for short-term use only, yet 68 percent of the users with drug-related injuries or problems were long-term users of zolpidem, on average taking a pill about 2 nights out of 3.
  • Despite the FDA’s recent recommendation that women and older adults be prescribed the lowest approved dose of the drug (5 mg zolpidem or 6.25 mg extended release), in 2012 (before the recommendation came out), few people were taking the lower dose.
  • Drug-drug interactions were common among regular users of zolpidem. Prescribing information warns against taking other drugs that depress the central nervous system while taking zolpidem. Yet about 22 percent of regular zolpidem users were also using opioids on a sustained-use basis. About 23 percent were taking another drug (a benzodiazepine, pregabalin, or gabapentin) that, like zolpidem, acts on the GABA system, producing complex effects.
  • Finally, the prescribing information for zolpidem says the drug may worsen depression and suicidal thoughts in patients with depression. Yet 34 percent of the regular users of zolpidem were also using an antidepressant.

Many regular users of zolpidem may never experience drug-related complications. (This may also have been the case for the majority of Halcion users.) But with so much data now showing that zolpidem is causing harm to significant numbers of users, prescribing patterns will likely change. Don’t be surprised if the next time you ask for a renewal of your zolpidem prescription, you’re prescribed something else instead.

If you use zolpidem for insomnia, how do you feel about the possibility of losing access to this sleeping pill?

Popular Sleeping Pills and Who’s Using Them

Some people I know are perfectly comfortable taking sleeping pills and would be happy to use them for the rest of their lives. Others say they’re harmful, having a raft of side effects and degrading the quality of sleep we get.

The pros and cons of sleeping pills are too numerous to explore in a blog (I do lay them out in The Savvy Insomniac, my book). But here’s a summary of the numbers of people using sleep meds in the US, which meds we’re using, and who’s using them.

popular sleeping pills and who uses themSome people I know are perfectly comfortable taking sleeping pills and would be happy to use them for the rest of their lives. Others say they’re harmful, having a raft of side effects and degrading the quality of sleep we get.

The pros and cons of sleeping pills are too numerous to explore in a blog (I do lay them out in The Savvy Insomniac, my book). But here’s a summary of the numbers of people using sleep meds in the US, which meds we’re using, and who’s using them. These statistics are based on data from the National Health and Nutrition Examination Survey, conducted from 1999 to 2010. Over 32,000 people in the general population participated in the survey.

Is Use of Prescription Sleeping Pills Really on the Rise?

Yes—or at least it was by the end of the survey. While about 2 percent of adults in the US used them in 1999-2000, the percent of adults using them in 2009-2010 was 3.5.

Many factors probably account for the change. More people are taking complaints of insomnia to their doctors (rather than assuming that nothing can be done), leading to a 7-fold increase in insomnia diagnoses. Many more people now are leaving the consulting room with a prescription in hand.

Which Prescription Medications Are We Using?

Trazodone, a sedating antidepressant never approved but often used for insomnia, was for many years physicians’ drug of choice for patients with sleep complaints. As of 2010 it was in second place, surpassed in popularity about a decade ago by zolpidem (a.k.a. Ambien), now leader of the pack. Of the 906 adults who reported having used a prescription sleep med in the past month,

  • 346 used zolpidem, eszopiclone (Lunesta), or zaleplon (Sonata)
  • 282 used trazodone
  • 154 used benzodiazepines such as temazepam (Restoril) or triazolam (Halcion)
  • 103 used quetiapine (Seroquel), an atypical antipsychotic prescribed off-label for insomnia, and
  • 45 used doxepin, a tricyclic antidepressant approved for insomnia as Silenor.

Of note is that fact that 58 percent of the adults who reported taking a pill to help with sleep did not endorse using a sleeping pill prescribed by the doctor. This suggests the use of over-the-counter sleeps aids like Zzzquil and Tylenol PM is huge.

Who Uses Prescription Sleep Medication?

We’re more likely to use the drugs listed above

  • as we grow older
  • if we’re female
  • if our income is equal to or above $75,000 a year
  • if we’re in poor health
  • if we’ve seen a mental health provider in the past year
  • if we’re also using another sedating medication prescribed for another condition
  • if we’re on Medicare or Medicaid, and
  • if we have arthritis.

What questions do you have about sleeping pills?

Q & A: Sleeping Pills for Use in the Wee Hours

A reader wrote to ask about sleeping pills for middle-of-the-night wake-ups.

“I don’t have a problem getting to sleep,” he explained. “I go jogging with my dog after work and that really tires me out. So I’m out by 10 or 10:30. But I have to go to the bathroom at least once a night, and then I can’t get back to sleep. Sometimes I wake up at 1:30 and I’m awake for the rest of the night! I’m about ready to give up and ask for a sleeping pill. Any thoughts?”

AsleepA reader wrote to Ask The Savvy Insomniac about sleeping pills for people who have trouble with insomnia in the middle of the night.

“I don’t have a problem getting to sleep,” he explained. “I go jogging with my dog after work and that really tires me out.  So I’m out by 10 or 10:30. But I have to go to the bathroom at least once a night, and then I can’t get back to sleep. Sometimes I wake up at 1:30 and I’m awake for the rest of the night! I’m about ready to give up and ask for a sleeping pill. Any thoughts?”

Intermezzo

If you decide to go the chemical route, Intermezzo, manufactured by Purdue Pharma, is an option for people with sleep maintenance insomnia (whose problem is awakening for stretches in the middle of the night). It’s a sublingual form of zolpidem (a.k.a. Ambien), and it comes in such low doses (1.75 and 3.25 mg) that it’s been approved by the FDA for use in the middle of the night. Dissolving a pill in the mouth is supposed to be a faster mode of delivery than swallowing the pill whole. Provided you still have four hours of shut-eye left, it’s not supposed to leave you feeling groggy in the morning.

But I’m put off by drug companies that repackage an old drug like zolpidem and then slap a brand name price on it. According to goodrx.com, 30 sublinguals of Intermezzo (3.5 mg) cost upwards of $225. That’s about $7.50 a pill! Fine and dandy for those who have good prescription drug coverage. But what about insomniacs who don’t?

Why not go with generic zolpidem, 5 mg, instead, and split each pill in half? (Pill splitters are free—just ask your pharmacist.) If you do it this way, the cost of getting back to sleep will be a mere 15 cents a night.

Zaleplon

Another option worth exploring with your doctor is zaleplon, the generic for the drug Sonata. This drug was never intended for use in the middle of the night, yet I hear talk about it from time to time. Zaleplon has a very short half-life (1 hour). An hour after you take this drug, the amount in your blood plasma is reduced by half. A drug that moves in and out of the system so quickly just might be safe for use in the middle of the night. Thirty capsules of zaleplon, 5 or 10 mg, cost about $20, or 66 cents a pill.

Doxepin, or Silenor

A third option for middle-of-the-night awakeners is Silenor. This drug, approved for sleep maintenance insomnia, operates on a different neurotransmitter system and is taken at the beginning of the night.

But once again, a pharmaceutical company (Somaxon) has taken an inexpensive generic drug (doxepin), reduced the dosage slightly, and is charging megabucks for the repackaging. According to goodrx.com, 30 Silenor tablets (which contain 6 mg of doxepin apiece) cost about $190—or $6.30 a pill. Contrast this with the cost of generic doxepin—just 23 cents per 10-mg capsule. When you consider that doxepin used as an antidepressant is sold in 150-mg capsules, the difference between a dosage of 6 and 10 mg of doxepin sounds rather slight. And the difference in price between the brand name drug and the generic is huge!

If your problem is waking up in the middle of the night, what have you found that helps you get back to sleep?

Ambien Gets Another Black Eye

As if it weren’t bad enough that Ambien, a.k.a. zolpidem, can cause sleepwalking, sleep eating, and sleep driving. Now researchers are saying that America’s favorite sleeping pill increases the retention of negative memories. This is not a good thing.

black-eyeAs if it weren’t bad enough that Ambien, a.k.a. zolpidem, can cause sleepwalking, sleep eating, and sleep driving. Now researchers are saying that America’s favorite sleeping pill increases the retention of negative memories. This is not a good thing.

Sleep generally helps you process negative events. Chances are you’ll never forget the fire that broke out in your kitchen, but sleep will help to diminish its emotional charge. You’ll wake up after a good night’s sleep in a more positive frame of mind.

But Ambien seems to interfere with this process. It does so by increasing sleep spindles—sudden bursts of electrical activity in the brain that may last up to a second. Overall, sleep spindles are beneficial. They play a role in helping to consolidate memories of facts and events. But the team that conducted this new research, led by psychologist Sara C. Mednick of UC Riverside, found that sleep spindles enhance the retention of emotionally charged memories as well—negative memories in particular.

Ambien’s Effects on Emotion

Researchers in this study divided their subjects into three groups. One group was given Ambien; the second, a placebo; and the third, Xyrem, another sedative drug. All subjects then looked at a series of images, some positive and others disturbing. Then they took naps. When they were awakened and asked to recall the images, the subjects that had taken Ambien remembered more images that had negative or highly arousing content. So the drug appears to enhance the recall of negative memories.

I use Ambien from time to time, and frankly I’m not surprised at this result. I love the little yellow pills for their unfailing ability to put me to sleep. But when my wakefulness is due to stress and emotional arousal, malaise is still with me the morning after I take a pill. Whatever good the Ambien does (and I’m still convinced the benefits outweigh the side effects, at least for me) it does not do a good job of helping regulate my mood.

So Ambien looks like a bad drug for people with anxiety disorders and PTSD. “These are people who already have heightened memory for negative and high-arousal memories,” Mednick said, quoted in an online article in Psych Central. “Sleep drugs might be improving their memories for things they don’t want to remember.”

All Ambien users—regardless of other health conditions—should keep this new information in mind.

If you use Ambien, how does taking a pill at night affect your mood the next day?