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


METHODS
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, double-blind clinical trials are indicated to further evaluate this medication in the treatment of PTSD.
Douglas Bremner
J
J
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30306, USA. jdbremn@emory.edu
Mletzko
Tanya
T
Welter
Silke
S
Siddiq
Sajid
S
Reed
Lai
L
Williams
Chanda
C
Heim
Christine M
CM
Nemeroff
Charles B
CB
D000927:Anticonvulsants / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006801:Humans; D010672:Phenytoin / Q000627:therapeutic use*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D016896:Treatment Outcome
D000927:Anticonvulsants; D010672:Phenytoin