The purpose of this study is to determine if modafinil is more effective than placebo in the treatment of posttraumatic stress disorder (PTSD) in male combat veterans who have been deployed to Iraq or Afghanistan.

There is a high rate of posttraumatic stress disorder (PTSD) in soldiers exposed to combat in Operations Enduring Freedom and Iraqi Freedom (OEF/OIF). Unfortunately, currently available treatments for combat-related PTSD have produced modest treatment gains at best. New treatment strategies that can be directed toward objectively measured correlates of PTSD are urgently needed.

Specific Aims: 1) To determine if there is evidence for the effectiveness and tolerability of adjunctive modafinil in the treatment of combat-related PTSD. We hypothesize that OEF/OIF veterans with PTSD randomized to modafinil 100mg/day for four weeks will experience more improvement in PTSD symptoms than OEF/OIF veterans with PTSD randomized to placebo treatment for four weeks. 2) To determine if PTSD symptom severity is associated with electrophysiological and neuropsychological measures of pre-attention and attention and if these measures change to a greater degree in participants randomized to modafinil versus those randomized to placebo. We hypothesize modafinil treatment will result in greater changes in electrophysiological and neuropsychological measures of pre-attention and attention than placebo treatment.

Inclusion Criteria:

• OEF/OIF Veteran with a history of deploying to Afghanistan or Iraq
• right-handed
• male 20-60 years of age
• meets Diagnostic and Statistical Manual (DSM-IV) diagnostic criteria for PTSD
• competent to give informed consent
• access to a telephone
• stable psychotropic medication regimen for a minimum of four weeks prior to enrollment
• able and willing to complete the required schedule of evaluations (Baseline in person, 1 week by phone, 2 week in person, 4 week in person)

Exclusion Criteria:

• diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder
• current substance abuse or dependence
• history of seizure disorder or severe traumatic brain injury
• history of attempted suicide within the previous two years or active suicidal ideation within the past month
• currently taking benzodiazepines except for bedtime dosing only
• currently taking stimulant medication
• known allergic reaction to modafinil or currently taking medication
• that may have altered metabolism if taken with modafinil: Tricyclic antidepressants (amitriptyline; nortriptyline; desipramine; imipramine; CNS stimulants (amphetamine; d-ampthetamine; atomoxetine); Carbamazepine; Phenytoin; Phenobarbitol; Rifampin; Ketaconazole; MAO Inhibitors (isoniazid; selegiline); Warfarin; Diazepam; Mephenytoin; Cyclosporine; Theophylline