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.

Sedating Antidepressants for Insomnia?

Antidepressants have been prescribed as de facto sleeping pills for over 3 decades now. This used to bother me. Most antidepressants have not been tested on people with simple insomnia and shown to improve their sleep.

These days I see things differently.

Can antidepressants help you sleep?Antidepressants have been prescribed as de facto sleeping pills for over 3 decades now. This used to bother me. Most antidepressants have not been tested on people with simple insomnia and shown to improve sleep.

In contrast, sleeping pills approved for the treatment of insomnia have been tested on insomniacs in clinical trials and shown to work. Why would a doctor prescribe a drug that hasn’t been held to the same standard? It looked like a cop-out to me.

These days I see things differently. Not because the pharmaceutical companies have suddenly come forward with proof that sedating antidepressants improve the sleep of people with insomnia in the absence of depression. (One such drug, low-dose doxepin, a tricyclic antidepressant, has been tested and approved for insomnia. Details are below.)

I’ve changed my mind for a personal reason: about 9 months ago, I was persuaded to start taking a low dose of a tricyclic antidepressant for a stomach problem I have. As a result, I can now eat small portions of many foods that were off-limits to me for 5 or 6 years.

Do I care that nortriptyline has never been tested and approved for the treatment of functional dyspepsia? No. Eating is believing. And now I’m willing to accept the idea that low-dose antidepressants might be a reasonable solution to the sleep problems of insomniacs who say they need medication to get a decent night’s sleep. Here’s some general information about sedating antidepressants and details about those frequently prescribed for people with insomnia.

Sedating Antidepressants

Doctors like antidepressants in part because of what they’re not. Most sleeping pills on the market today—zolpidem (Ambien), eszopiclone (Lunesta), and suvorexant (Belsomra), for example—are Schedule IV drugs, meaning that they’re believed to have some potential for abuse and dependence. Nightly users of these drugs may also develop tolerance to them and find they no longer work.

In contrast, antidepressants are unscheduled drugs not known to foster dependency or abuse. They’re considered relatively safe for long-term use. If you find one that helps you manage your insomnia, your doctor will probably be happy to prescribe it indefinitely.

The downside of many sedating antidepressants is that they have side effects at the high doses typically prescribed for people with depression. Drowsiness, increased susceptibility to falls, cognitive impairment, weight gain, dry mouth, constipation, difficulty with urination, and fine tremor are adverse effects noted by significant numbers of users. In the absence of formal testing, it’s hard to predict how frequently these adverse effects would occur at the low doses prescribed for people with insomnia.

Doxepin (Silenor)

As mentioned above, this is the only antidepressant approved for the treatment of insomnia. Doxepin at doses prescribed for depression (over 75 mg) acts on several neurotransmitter systems. At the low dose typically prescribed for insomnia (less than 10 mg), its sole appreciable effect is to block secretion of histamine, a neurotransmitter associated with wakefulness.

Strengths and weaknesses, per a review of randomized placebo-controlled trials:

  • Doxepin is better than placebo at keeping people sleeping through the night, extending sleep time, and improving sleep efficiency. The higher the dose, the more marked are the effects.
  • Doxepin does not help with sleep initiation. Headache and grogginess are possible side effects.

Trazodone (Desyrel)

Trazodone is the sedating antidepressant most commonly prescribed for people diagnosed with insomnia in the United States. At the low dose typically prescribed for sleep (50 mg), its blockade of histamine, serotonin, and alpha-1 receptors likely gives this drug its sedative effects. Trazodone’s popularity as a hypnotic is based on little hard evidence. No long-term studies of the drug’s efficacy as a hypnotic exist. This is unfortunate because it’s generally used as a maintenance treatment for people with insomnia.

Short-term trials obtained the following results:

  • In a large, 2-week trial comparing 50 mg trazodone with 10 mg zolpidem and placebo, trazodone in the first week reduced wakefulness at night and improved total sleep time and sleep quality. The drug performed no better than placebo in the second week.
  • In a small week-long trial of 50 mg of trazodone conducted to assess the drug’s side effects, investigators found that compared with placebo, trazodone cut down on nighttime awakenings and stage 1 sleep (the lightest stage). On day 7 only, subjects got more deep sleep and experienced less sleepiness the following day. However, taking the drug also led to “small but significant impairments of short-term memory, verbal learning, equilibrium, and arm muscle endurance across time points.” How likely these side effects would be to occur with long-term use is unknown.

Mirtazapine (Remeron)

Mirtazapine is a tetracyclic antidepressant also used for insomnia. This drug has never been tested on people with simple insomnia. But in 15 to 45-mg doses, it’s been found to have sedative effects in people with depression and insomnia. This is likely due to the drug’s blockade of histamine and serotonin receptors.

Strengths and weaknesses, per short- and long-term trials conducted on people with depression and insomnia (most of these trials did not have a placebo or FDA-approved control) :

  • Mirtazapine helps with falling asleep and staying asleep and may improve sleep quality.
  • Mirtazapine may potentially cause weight gain. Other common side effects include daytime drowsiness or dizziness and dry mouth.

According to a review article in the Journal of the American Pharmacists Association, “Lower doses (e.g., 7.5–15 mg) of mirtazapine may actually provide more sedation when compared with higher doses, as higher doses . . . [may blunt] the drug’s sedative effect.”

Amitriptyline (Elavil)

Amitriptyline is a tricyclic antidepressant that is sometimes prescribed in low doses (5–25 mg) for people with insomnia and other chronic health conditions. No clinical trials of the drug’s efficacy as a treatment for insomnia have ever been conducted. But studies conducted on people with depression and healthy individuals have found that amitriptyline has sedative effects.

Common side effects are daytime drowsiness, dry mouth, and urinary problems.

The Take-Away

The point of this blog is not to suggest that sedating antidepressants are a good solution to the sleep problems of everyone with persistent insomnia. My point is that these drugs may be a viable option for people who haven’t found relief through other means.

If you’ve tried an antidepressant for sleep, what was your experience like?

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?

Pregabalin for Insomnia: A Viable Off-Label Option?

Sleeping pills approved by the Food and Drug Administration–Ambien and Lunesta–are getting some negative press these days, and I hear more talk of using off-label medications to treat insomnia. (Off-label meds are drugs approved for the treatment of other disorders.) I’ve blogged about some of these drugs before: trazodone, clonazepam and quetiapine.

Pregabalin is another, which is now being prescribed for people with trouble waking up in the middle of the night.

off-label-drugSleeping pills approved by the Food and Drug Administration–Ambien and Lunesta–are getting some negative press these days, and I hear more talk of using off-label medications to treat insomnia. (Off-label meds are drugs approved for the treatment of other disorders.) I’ve blogged about some of these drugs before: trazodone, clonazepam and quetiapine.

Pregabalin is another. Recently I saw a video interview of Thomas Roth, who directs the Sleep Disorders and Research Center at Henry Ford Hospital in Detroit, following a professional conference early this month. Asked about insomnia treatments, Roth mentioned two drugs for people with sleep maintenance insomnia (trouble waking up in the middle of the night):

  • Low-dose doxepin, a tricyclic antidepressant approved by the FDA for sleep maintenance insomnia under the brand name Silenor in 2010, and
  • Pregabalin, an anticonvulsant approved to treat neuropathic pain, epilepsy, and fibromyalgia in the US and for generalized anxiety disorder (GAD) in Europe and Russia.

Lots of people come to The Savvy Insomniac looking for information about sleeping pills and supplements, and sleep maintenance insomnia is the most common type of insomnia problem. So I decided to investigate pregabalin. Here’s what I found out.

Is Pregabalin Effective for Trouble Sleeping?

There haven’t been any controlled trials of pregabalin as a treatment for insomnia per se. But one main side effect of the drug is drowsiness. In chemical structure, pregabalin is similar to GABA, a neurochemical that tranquilizes the brain at night. (But unlike Ambien, Lunesta, and benzodiazepines such as temazepam and clonazepam, pregabalin does not bind directly to GABA or benzodiazepine receptors.)

Insomnia and anxiety are closely linked, and pregabalin inhibits the release of neurotransmitters associated with anxiety. Reviewers looking at the effects of the drug on people with anxiety and insomnia found that the drug improved subjects’ sleep in seven controlled clinical trials.

But the kind of insomnia most often associated with anxiety is trouble getting to sleep at night. Why might pregabalin be effective for people whose problem is that they can’t stay asleep?

The elimination half-life of pregabalin is about 6 hours. So it’s longer lasting than many sleeping pills on the market today, and certainly longer lasting than over-the-counter melatonin supplements. Reviewers of pregabalin’s effects on sleep disturbance associated with other disorders say, based on data from overnight sleep studies, that pregabalin improves sleep and “primarily affects sleep maintenance.”

Is Pregabalin Safe?

Research on pregabalin used in the treatment of other disorders suggests the drug is relatively safe. The two most common side effects of the drug are drowsiness and dizziness. But few randomized, controlled trials have been conducted to determine its long-term safety, though the drug has been on the market since 2005.

Like most prescription sleeping pills, pregabalin is a controlled substance. But it is classified as a Schedule V drug, considered by the FDA and the Drug Enforcement Administration to have a lower potential for abuse and dependence than benzodiazepines like temazepam and clonazepam and Ambien and Lunesta, which are Schedule IV drugs.

If sleep maintenance is your problem and you’re unable to manage it by other means, pregabalin might be worth checking into with your doctor.

If you’ve already tried pregabalin, what effect did it have on your sleep?

Insomnia in the Middle of the Night

Does your sleep problem involve waking up in the middle of the night once or several times and then trouble falling back to sleep? Sleep maintenance insomnia is actually the most common form of insomnia, and it’s more common as people age. Here’s a quick review of the possible causes and what can be done.

sleep-maintenance-insomniaDoes your sleep problem involve waking up in the middle of the night once or several times and then trouble falling back to sleep? Sleep maintenance insomnia is actually the most common form of insomnia, and it’s more common as people age. Here’s a quick review of the possible causes and what can be done.

Having to pay a bathroom call at night will of course wake you up. Anything you can do cut down on the need to do that—eating an earlier dinner, drinking less in the evening, changing the time you take a medication (with an OK from the doctor)—will help. Other possible reasons for unwanted wake-ups include:

  • Age-related degeneration of neurons connected with the body clock. This results in weaker circadian rhythms, declining levels of melatonin (a hormone helpful to sleep), and more frequent shifts between sleep and waking.
  • Health problems involving chronic pain.
  • A higher rate of “cyclic alternating patterns”—repetitive brainwave patterns that occur during non-REM, or quiet, sleep, which cause your sleep to become less stable.

Reducing Nighttime Wake-ups

I’ll start by describing a behavioral strategy that may be helpful and then move on to medication.

  • Consolidate your sleep by reducing your time in bed. This is one key aim of Sleep Restriction Therapy, which I’ve blogged about many times. Simply delay your bedtime for an hour or more while continuing to get up at the same time every morning. Research suggests that the increased sleep pressure that builds up when you postpone bedtime will cut down on wake-ups at night. This strategy is known to work for adults of all ages.
  • If you suspect that a lack of melatonin is involved, you could ask your doctor about testing for melatonin deficiency (blood, urine, or saliva tests will work). You could also buy a test kit online, collect a sample and send it away to a lab yourself (I don’t, however, have information on the reliability of these labs). If your middle-of-the-night wake-ups are related to a melatonin deficiency, my blog on Melatonin Replacement Therapy describes the treatment options that exist–none perfect.

Prescription Medication

Many doctors frown on the nightly use of hypnotics. Although the FDA has approved a few of them for use without short-term restriction (Lunesta and Ambien CR, for example), concerns about side effects and the potential of these sleeping pills to cause drowsiness in the morning make physicians leery of prescribing them. This is especially true for older patients, whose bodies process drugs more slowly and who are thus more likely to experience unwanted effects.

As occurred in the 1980s and 1990s, physicians are now prescribing more sedating antidepressants and antipsychotics for patients with sleep maintenance insomnia. (Unfortunately, there have been few controlled studies assessing the efficacy of these drugs for insomnia.) Here are some examples:

  • Silenor. This low-dose formulation of doxepin is the single antidepressant drug that has been approved by the FDA for the treatment of sleep maintenance insomnia. Controlled studies have shown that it cuts down on nighttime wake-ups. The brand-name drug is expensive; generic doxepin is chemically identical and will work just as well . . . if it does work.
  • Trazodone. This sedating antidepressant was the best-selling drug for insomnia until the turn of the 21st century (and may now enjoy renewed popularity). The few short-term studies of the drug as a treatment for insomnia suggest that low doses (100 mg or less) cut down on wake time in the middle of the night. See my blog on trazodone for details.
  • Seroquel and Klonopin. See my blog on Off-Label Meds for Insomnia for information on these drugs. Here I’ll offer an addendum: the fact that these drugs are now available as generics (and therefore inexpensive) makes it unlikely that they’ll ever be tested for efficacy in treating insomnia. They may be effective for sleep maintenance insomnia—but any evidence now is based on observation only.

One last note on medication for middle-of-the-night awakeners: The sleeping pill zaleplon (a.k.a. Sonata) has not been approved for use in the middle of the night. But it has a very short half-life (1 hour) and tests are under way to evaluate the safety of middle-of-the-night dosing. A new study shows that while Ambien CR taken at bedtime interfered with the consolidation of memories at night, 10 mg of zaleplon taken in the middle of the night did not. Other studies have shown no residual grogginess in insomniacs at 4 hours after taking zaleplon. The drug may be an option for those looking to get back to sleep more quickly.

If you have sleep maintenance insomnia, what strategies and medications have you tried, and have they worked?

A New Look at Trazodone for Sleep

Trazodone has never been approved for the treatment of insomnia. Yet it rose to the top of the bestseller charts as a medication for sleeplessness in the 1990s and enjoys great popularity still. Here’s one explanation for its appeal.

It’s been a stretch for me to accept that trazodone, a sedating antidepressant, is such a popular treatment for insomnia. Clinical trials have never shown it helps put people to sleep or keeps them sleeping longer. And even at low doses (50 mg.), the drug is known to produce cognitive and motor impairments the following day.* Trazodone has never been approved for the treatment of insomnia, yet it rose to the top of the bestseller charts as a medication for sleeplessness in the 1990s and enjoys great popularity still.

Trazodone

Confession: this is the sort of knotty paradox that keeps me awake at night.

Now, I have insomniac friends who swear by trazodone, and I know they’re not delusional. They use low-dose trazodone because it works for them, and they don’t need to understand why.

But I’m a stickler for evidence, and this gap between subjective experience and objective proof is a real sore point. So imagine my thrill at finding a paper that explains why it might be that trazodone works.

Trazodone and REM Sleep

The traditional view of insomnia holds that it’s basically a problem of non-REM (or quiet) sleep. Insomniacs may not be getting the same percent of deep sleep as good sleepers, or the problem may be in how deep sleep is discharged. Deep sleep is the restorative stuff, the kind that “knits up the raveled sleeve of care.” Alternatively, the quality of non-REM sleep may be compromised by lots of high-frequency brain activity that enables you to sense things even while you’re asleep.

But for insomniacs who struggle with frequent awakenings in the middle of the night, the problem may in fact be occurring during REM (or active) sleep, when you’re dreaming. A new analysis shows that percent-wise, people with sleep maintenance insomnia get less REM sleep and awaken more often during REM sleep than good sleepers. The hypothesis is that these insomniacs may be suffering from “REM sleep instability.”**

Despite its otherwise underwhelming characteristics as a sleep medication, trazodone does cut down on nighttime awakenings and make sleep feel easier. Unlike most other antidepressants, the drug does not suppress REM sleep. So as a sleeping pill, trazodone may have a claim to legitimacy after all.

Perhaps you’re one who knew it all along, but I was a skeptic, and this bit of news has done wonders for my sleep!

Effects of Trazodone

** REM Sleep Instability