Treatment of posttraumatic stress disorder with phenytoin: An open-label pilot study

J. Douglas Bremner, Tanya Mletzko, Silke Welter, Sajid Siddiq, Lai Reed, Chanda Williams, Christine M. Heim, Charles B. Nemeroff

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Background: Phenytoin is an anticonvulsant used in the treatment of epilepsy. Its mechanism of action is incompletely understood but most likely involves modulation of glutamatergic transmission. The neurobiology of posttraumatic stress disorder (PTSD) has been hypothesized to involve, at least in part, alterations in glutamatergic transmission in the hippocampus and possibly other brain regions. The purpose of this study was to assess the effects of phenytoin on symptoms of PTSD. Method: Phenytoin was administered in an open-label fashion for 3 months to 9 adult male and female patients with DSM-IV PTSD related to a variety of traumas including childhood abuse, combat, and car accidents. Dosage was adjusted to maintain the therapeutic blood levels used in the treatment of epilepsy. Subjects were assessed before, during, and after treatment for PTSD with standardized dimensional measures of disease severity including the Clinician Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton Rating Scale for Anxiety (HAM-A). Data were collected from November 2001 through June 2003. Results: Phenytoin treatment resulted in a significant decrease in PTSD symptoms as measured with the CAPS (mean score = 65 pretreatment vs. 38 posttreatment) with reductions in each of the symptom clusters of intrusions, avoidance, and hyperarousal (p < .05). There were no significant decreases in symptoms of depression severity as measured with the HAM-D or anxiety severity as measured with the HAM-A. Conclusions: These findings suggest that phenytoin may be efficacious in the treatment of PTSD, possibly mediated through its antiglutamatergic effects. Randomized, controlled, doubleblind clinical trials are indicated to further evaluate this medication in the treatment of PTSD.

Original languageEnglish (US)
Pages (from-to)1559-1564
Number of pages6
JournalJournal of Clinical Psychiatry
Issue number11
StatePublished - Nov 2004
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


Dive into the research topics of 'Treatment of posttraumatic stress disorder with phenytoin: An open-label pilot study'. Together they form a unique fingerprint.

Cite this