Sedating Antidepressants for Insomnia?

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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?