Modafinil in the Treatment of PTSD (Posttraumatic Stress Disorder)

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