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Effects of phenytoin on memory, cognition and brain structure in post-traumatic stress disorder: a pilot study

Departments of Psychiatry and Behavioral Sciences, Radiology and Emory Center for Positron Emission Tomography, Emory University School of Medicine, Atlanta and Atlanta VAMC, Decatur, GA, USA, jdbremn{at}emory.edu

Tanja Mletzko

Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA

Silke Welter

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

Sinead Quinn

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

Chanda Williams

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

Marijn Brummer

Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA

Sajid Siddiq

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

Lai Reed

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

Christine M. Heim

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

Charles B. Nemeroff

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

Phenytoin (Dilantin®) is an anticonvulsant used in the treatment of epilepsy. It is believed to act by modulation of glutamatergic transmission. Because the neurobiology of post-traumatic stress disorder (PTSD) has been hypothesized to involve alterations in glutamatergic transmission with subsequention neurotoxicity, we assessed the effects of phenytoin on cognition and brain structure in PTSD patients. Phenytoin was administered in an open label fashion for 3 months to nine adult patients with PTSD related to a variety of traumas, including early abuse, combat and car accidents. Subjects underwent magnetic resonance imaging for measurement of whole brain and hippocampal volume, and neuropsychological testing of memory and cognition, before and after treatment. Phenytoin treatment resulted in a significant 6% increase in right brain volume (p < 0.05). Increased hippocampal volume was correlated with reductions in symptom severity as measured by the Clinician Administered PTSD Scale and improvements in executive function as measured by the Trails test. However, treatment associated improvements in memory and cognition did not achieve statistical significance. These findings suggest that phenytoin treatment may be associated with changes in brain structure in patients with PTSD.

Key Words: hippocampus • pharmacology • phenytoin • PTSD • stress • treatment

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				J. D. BREMNER The Relationship Between Cognitive and Brain Changes in Posttraumatic Stress Disorder Ann. N.Y. Acad. Sci., July 1, 2006; 1071(1): 80 - 86. [Abstract] [Full Text] [PDF]