Trazodone for Disturbed Sleep Initiation in PTSD

David N. Osser, MD

Associate Professor of Psychiatry
Harvard Medical School
Brockton Division of the VA Boston Healthcare System

Last updated: December 5, 2017

In this video, Dr. David Osser reviews the evidence base for the use of trazodone in PTSD patients with disturbed sleep initiation.

He also comments on side effects, with a focus on priapism.

This video is an excerpt from the presentation “Psychopharmacology of PTSD Algorithm”. The full presentation is available for Premium Members of our CME program

You have completed the initial evaluation and you have considered whether the patients have sleep disturbance that could be from the PTSD. You have considered a trial of prazosin.

So, what if sleep smoothness through the night is improved, but they still have trouble initiating sleep? This is Node 2b of the algorithm.

They still have trouble falling asleep, even though they are doing better with their nightmares and disturbed awakenings.

Our first-choice option for helping them fall asleep is trazodone. I’m sure you are familiar with trazodone, it is a sedating antidepressant. It has shown some effectiveness for sleep disturbances in PTSD, but only in open-label studies.

 

It has been described as an “ideal hypnotic agent” by Stephen Stahl because of its triple sleep-promoting actions on the 5-HT2A, alpha 1, and H1 receptors.

 

It also has a short half-life, no weight gain, low risk of dependence, no problems with sexual side effects. It has a lot of things that make it a relatively ideal choice for many patients.

 

It has a reasonable role, we think, to add to prazosin, or instead of it, if there really are no problems with nightmares but just difficulty falling asleep.
If prazosin was not effective, you could consider trying it for the total picture. For the falling asleep and the difficulties maintaining sleep because of the nightmares, before moving on to the SSRIs. But I have to say the evidence for it is pretty minimal. It is pretty much clinical experience all we have as a solo treatment for the major symptoms of PTSD.

As far as what evidence we do have with trazodone, there is one open-label study. What I do offer, though, is two studies of using trazodone versus placebo for SSRI-induced insomnia.

SSRIs, as noted, often cause insomnia as a side effect, maybe in 15 or 20% of patients, and in two randomized control trials, trazodone was an excellent treatment for that.

It also has been compared with zolpidem for primary insomnia. It was in a large trial which also had a placebo control, and it proved comparable in efficacy for primary insomnia.There is a variety of lines of evidence that trazodone is a reasonable insomnia treatment that you might apply in this situation.

 The side effects of trazodone include excess sedation, dizziness, orthostatic problems occur from time to time, and syncope occasionally. You do have to be cautious and watch for that.
 

Perhaps the most often-mentioned side effect in males is priapism, and that is a concern. It is an infrequent concern. Serious priapism only occurs in 1 in 2000 or 3000 patients, but you do need to warn people about it, and in theory the risk of priapism may be increased if you combine trazodone with prazosin.

Some have thought that you shouldn’t combine prazosin with trazodone, because of a possible increased risk of priapism. So far, there has not been any reported cases of priapism in this commonly-used combination. Nevertheless, extra caution and warning about priapism are certainly necessary when combining them, and we do that routinely.

Trazodone is usually started at 50 mg at bedtime, with instructions to reduce to 25 mg if it is too sedating. Sometimes people have done well with just 12.5 mg.

References

  1. Stahl SM. Mechanism of action of trazodone: a multifunctional drug. CNS Spectr 2009;14:536–46
  2. Hertzberg MA, Feldman ME, Beckham JC, Davidson JR. Trial of trazodone for posttraumatic stress disorder usinga multiple baseline group design. J Clin Psychopharmacol 1996;16:294–8
  3. (Warner, 2001; Kaynak, 2004; Nierenberg, 1994;)
  4. Walsh JK. Subjective hypnotic efficacy of trazodone and zolpidem in DSM III–R primary insomnia. Hum Psychopharmacol 1998;13:191–8
  5. Warner MD, Dorn MR, Peabody CA. Survey on the usefulness of trazodone in patients with PTSD with insomnia or nightmares. Pharmacopsychiatry 2001;34:128–31.

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