Zolpidem for Insomnia Related to PTSD

To the Editor: Chronic sleep difficulties, including reduced total sleep time and nightmares, are often a chief complaint of combat veterans with posttraumatic stress disorder (PTSD) (1). Trazodone, doxepin, and benzodiazepines can be used to treat insomnia in these patients (2). Benzodiazepines have the disadvantage of potential addiction or tolerance. Trazodone and doxepin can cause a morning hangover feeling, and tolerance to their sedative properties may occur.

Zolpidem is a nonbenzodiazepine imidazopyridine compound with unique characteristics that may confer advantages over conventional medications for sleep induction and maintenance in PTSD. It has a rapid onset, a short duration of action, and a low incidence of adverse effects. Zolpidem appears to have low addictive potential and few drug interactions (3). It is not associated with rapid eye movement (REM) rebound or tolerance (4). We have prescribed zolpidem for more than 50 veterans with PTSD and chronic sleep complaints, as illustrated by the following examples.

Case 1. The patient was a 50-year-old male Vietnam veteran with PTSD as diagnosed by the Clinician-Administered PTSD Scale (5). He also had major depression and alcohol dependence in full remission. The patient reported sleeping between one and four hours a night and experiencing frequent nightmares. Venlafaxine 75 mg a day and trazodone titrated up to 200 mg at bedtime were initiated. Trazodone was effective at higher doses, but a residual hangover effect occurred. Substituting zolpidem 10 mg at bedtime for the trazodone helped the patient gain two to three hours of sleep per night. He developed no side effects or tolerance in nine months on zolpidem.

Case 2. The patient, a 63-year-old male Korean War veteran with PTSD, had taken fluoxetine and clonazepam for the past six years; the most recent dosage was fluoxetine 40 mg per day and clonazepam .5 mg twice a day. He complained of receiving only three to four hours of intermittent sleep per night. Trazodone and doxepin were tried for insomnia but exacerbated the patient's restless leg syndrome and were therefore discontinued. Zolpidem 10 mg at bedtime was initiated, resulting in the patient's getting six or more hours of sleep a night. No loss of efficacy or side effects were noted in ten months of use of zolpidem on a nightly basis.

Case 3. The patient, a 52-year-old male Vietnam combat veteran diagnosed with PTSD by the Clinician-Administered PTSD Scale, reported severe nightmares nightly in which he awoke sweating profusely, was "ready to shoot at the enemy," and was unable to go back to sleep. He slept a total of two to four hours a night. He was treated with nefazodone 150 mg twice a day and risperidone 5 mg at bedtime. However, he felt oversedated, and one month later zolpidem up to 20 mg was substituted for risperidone. Subsequently, the patient's sleep maintenance improved, the frequency and intensity of his nightmares decreased, and he reported feeling well rested. He showed no evidence of tolerance after taking zolpidem nightly for 13 months.

We have used zolpidem for many veterans with PTSD-associated insomnia. Of the first 32 PTSD patients treated with zolpidem in our clinic, 25 remain on zolpidem and report an improvement in insomnia with no side effects. Some have taken zolpidem for as long as 20 months. The other seven PTSD patients discontinued zolpidem due to lack of efficacy; none discontinued it due to adverse effects.

Our clinical experience indicates that zolpidem is beneficial in treating PTSD-associated insomnia in most veterans and in alleviating nightmares in some veterans with PTSD. Controlled studies are needed to more fully elucidate the impact of zolpidem on insomnia, nightmares, and other symptoms of PTSD.