What’s That Antidepressant Doing to Your Sleep?

Most—but not all—antidepressants tend to suppress and/or delay REM sleep (the stage associated with dreaming). This can be helpful for people with depression.

It’s not necessarily helpful for people with insomnia. In fact, REM sleep irregularities may be a causal factor in insomnia. So it pays to know a bit more about antidepressants if you’re taking them now or before you head down that path.

Most antidepressants suppress and delay REM sleepAntidepressants are the third most commonly taken medication in the United States today, prescribed for depression and health problems such as insomnia, pain, anxiety, headaches, and digestive disorders. Most—but not all—antidepressants tend to suppress and/or delay REM sleep (the stage associated with dreaming). This can help people with depression.

It’s not necessarily helpful for people with insomnia—or for people who might be inclined to sleep problems if pushed in the wrong direction. There’s mounting evidence that REM sleep irregularities may actually be a causal factor in insomnia. So it’s worthwhile knowing about the REM and other sleep effects of antidepressants if you’re taking them now or before you head down that path.

Importance of REM Sleep

Intact, sufficient REM sleep has many benefits. They include the enhancement and consolidation of learned tasks and skills in long-term memory and the regulation of emotion.

Fragmented REM sleep, in contrast, may lead to the inadequate processing of emotion and then to hyperarousal, in turn giving rise to insomnia. Loss of the final REM period, a phenomenon identified in some “short sleepers” (often defined as those who sleep less than 5 hours a night), may increase your appetite and make you more vulnerable to weight gain and obesity.

In short, reduced or compromised REM sleep is not something you generally want.

Selective Serotonin Reuptake Inhibitors (and Relatives)

SSRIs are widely prescribed because they’re effective for depression and have relatively few major side effects. But as a class, they tend to suppress REM sleep. (They may also bring about changes in the frequency, intensity, and content of your dreams.) They also tend to delay the onset of sleep and increase awakenings and arousals at night, reducing sleep efficiency.

If you have both depression and insomnia, it’s probably best to steer clear of SSRIs. But here’s a caveat. SSRIs and other drugs that act on the serotonin system (which is very complex) are known to have different sleep–wake effects on different people. Trying out a drug like fluoxetine (Prozac) may be the only way to ascertain for sure how it will affect your sleep.

The story is basically the same for serotonin and norepinephrine reuptake inhibitors (SNRIs). Drugs such as duloxetine (Cymbalta) and venlafaxine (Effexor XR) markedly suppress REM sleep and tend to disrupt sleep continuity.

Tricyclic Antidepressants

TCAs aren’t prescribed as often as SSRIs because they tend to cause more side effects. However, like SSRIs, most TCAs (except trimipramine) markedly suppress REM sleep. Also, TCAs like desipramine and protriptyline give rise to increased norepinephrine, which tends to promote wakefulness rather than sleep. In studies of desipramine, the drug degraded the sleep of people with depression by extending sleep onset latency, decreasing sleep efficiency, and increasing their number of awakenings at night.

Most TCAs are not sleep friendly. However, low-dose amitriptyline is known to have sedative effects and is sometimes prescribed for people with depression and insomnia.

Low-dose doxepin has been shown to have sedative effects as well, blocking secretion of histamine, a neurotransmitter associated with wakefulness. Sold today as Silenor, it’s the only antidepressant approved by the FDA for the treatment of insomnia. Clinical trials suggest that Silenor is effective in treating sleep maintenance insomnia but not insomnia that occurs at the beginning of the night.

Atypical Antidepressants

Some antidepressants are atypical in that they don’t fit neatly into any category. Although not approved for the treatment of insomnia (the requisite trials were never conducted), low-dose trazodone (Desyrel) and mirtazapine (Remeron) are often prescribed for people with insomnia because of their sedative effects. Unlike most antidepressants, these drugs have not been found to markedly suppress REM sleep. And the results of a very few studies suggest that they may help people fall asleep more quickly and sleep more deeply.

If you’re taking an antidepressant now (for whatever reason) and you think it may be interfering with your sleep, talk about it with your doctor. And if you’re having sleep problems and considering an antidepressant, be selective about the one you use.

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?