0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
Posttraumatic Stress Disorder and Sleep Difficulty
SCOTT JACOBS-REBHUN, M.D.; PAULA P. SCHNURR, PH.D.; MATTHEW J. FRIEDMAN, M.D., PH.D.; ROBERT PECK, M.D.; MICHAEL BROPHY, M.D.; DWAIN FULLER, B.S.
Am J Psychiatry 2000;157:1525-1526. doi:10.1176/appi.ajp.157.9.1525

To the Editor:

Patients with posttraumatic stress disorder (PTSD) frequently report difficulty falling asleep, decreased sleep duration, and trauma-related nightmares. Effective pharmacotherapeutic treatments for these problems have not been identified. Open-label trials suggest that cyproheptadine may be a promising treatment (1, 2). Cyproheptadine acts as a histamine 1 (H1) and serotonin 2 (5-HT2) receptor antagonist. Evidence indicates that 5-HT2 antagonists increase stages of slow-wave sleep without altering total sleep time (3) and improve sleep outcome (4).

We conducted a double-blind, randomized, placebo-controlled trial of cyproheptadine for treating sleep problems found in PTSD. The participants were male Vietnam veterans who had current combat-related PTSD according to the Clinician Administered PTSD Scale (5) and who also reported at least moderately severe nightmares on the Pittsburgh Sleep Quality Index (6). The exclusion criteria included current substance abuse, use of a selective serotonin reuptake inhibitor, mania or hypomania, and any medical condition that contraindicated the use of cyproheptadine. After complete description of the study to subjects, written informed consent was obtained. Sixty-nine subjects were enrolled in this 2-week trial across two sites. Posttreatment data on the Clinician Administered PTSD Scale, the Pittsburgh Sleep Quality Index, and a nightmare questionnaire were available for 60 subjects.

The drug and placebo groups did not differ at pretreatment on severity scores on the Clinician Administered PTSD Scale (F=2.06, df=1, 56, p=0.16), total scores on the Pittsburgh Sleep Quality Index (F≈0.00, df=1, 56, p≈1.00), or nightmare severity (F=2.80, df=1, 56, p=0.10). When adjusted for pretreatment scores by analysis of covariance, posttreatment scores on the Clinician Administered PTSD Scale (F=0.06, df=1, 55, d=0.14, p=0.81) and scores for nightmare severity (F=1.92, df=1, 55, d=0.37, p=0.17) were nonsignificantly higher (worse) in the treatment group than in the placebo group, and scores on the Pittsburgh Sleep Quality Index showed marginally poorer sleep in the treatment group than in the placebo group (F=3.68, df=1, 55, d=0.58, p=0.06). Cyproheptadine serum levels (determined by gas chromatography/mass spectrometry) were available at one site for 14 of 15 treated subjects. Partial correlation analysis, controlling for pretreatment scores, showed a marginally significant correlation of higher cyproheptadine levels with a worsening of Pittsburgh Sleep Quality Index scores (r=0.47, p=0.051) but no significant correlation with scores on the Clinician Administered PTSD Scale (r=0.21, p=0.25) or scores for nightmare severity (r=0.24, p=0.22) (in one-tailed tests).

Contrary to expectation (1, 2), cyproheptadine does not appear to be an effective treatment for sleep problems or combat-related PTSD and may even exacerbate sleep disturbance. Although the study group was relatively small, low power is an unlikely explanation for our nonsignificant findings because of the trend for poorer sleep in the treatment group and the likely correlation of cyproheptadine levels with worsening of sleep. Our results reinforce the need for skepticism about open-label or anecdotal findings and for careful scientific trials to replicate uncontrolled studies.

Brophy MH: Cyproheptadine for combat nightmares in post-traumatic stress disorder and dream anxiety disorder. Mil Med  1991; 156:100–101
[PubMed]
 
Harsch HH: Cyproheptadine for recurrent nightmares (letter). Am J Psychiatry 1986; 143:1491–  1492
 
Idzikowski C, Mills F, Glennard R:5-Hydroxytryptamine-2 antagonist increases human slow wave sleep. Brain Res  1986; 378:164–168
 
Adam K, Oswald I: Effects of repeated ritanserin on middle-aged poor sleepers. Psychopharmacology (Berl)  1989; 99:219–221
[PubMed]
[CrossRef]
 
Blake DD, Weathers F, Nagy LM, Kaloupek DG, Klauminzer G, Charney DS, Keane TM: The development of a clinician-administered PTSD scale. J Trauma Stress  1995; 8:75–90
[PubMed]
[CrossRef]
 
Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ: The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res  1989; 28:193–213
[PubMed]
[CrossRef]
 
+

References

Brophy MH: Cyproheptadine for combat nightmares in post-traumatic stress disorder and dream anxiety disorder. Mil Med  1991; 156:100–101
[PubMed]
 
Harsch HH: Cyproheptadine for recurrent nightmares (letter). Am J Psychiatry 1986; 143:1491–  1492
 
Idzikowski C, Mills F, Glennard R:5-Hydroxytryptamine-2 antagonist increases human slow wave sleep. Brain Res  1986; 378:164–168
 
Adam K, Oswald I: Effects of repeated ritanserin on middle-aged poor sleepers. Psychopharmacology (Berl)  1989; 99:219–221
[PubMed]
[CrossRef]
 
Blake DD, Weathers F, Nagy LM, Kaloupek DG, Klauminzer G, Charney DS, Keane TM: The development of a clinician-administered PTSD scale. J Trauma Stress  1995; 8:75–90
[PubMed]
[CrossRef]
 
Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ: The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res  1989; 28:193–213
[PubMed]
[CrossRef]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 20

Related Content
Books
Textbook of Traumatic Brain Injury, 2nd Edition > Chapter 35.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 18.  >
Textbook of Traumatic Brain Injury, 2nd Edition > Chapter 39.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 47.  >
Dulcan's Textbook of Child and Adolescent Psychiatry > Chapter 22.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles