Intervention: Riluzole
Trial phase: Phase 1 | Phase 2
ATC code: N07XX02
SMILES: Nc1nc2ccc(OC(F)(F)F)cc2s1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 37
Group description: Weeks 1 and 2: Riluzole 50 mg tablet by mouth every 12 hours (100 mg/day) for 2-weeks

Weeks 3 to 8 (optional dose increase): 2 Riluzole 50 mg tablets by mouth every 12 hours (200 mg/day) for 6-weeks
Eligibility criteria:
Inclusion Criteria:

Active-duty service member or an Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), or Operation New Dawn (OND) veteran.
Clinical diagnosis of PTSD and have not achieved remission with an adequate trial of medication treatment (8 weeks) as indicated by self-report at referral and confirmed by baseline CAPS score of greater than or = to 40 after informed consent is obtained.

Exclusion Criteria:

Female subjects of childbearing capacity who test positively for ß-HCG, or are either self-reporting as pregnant, planning to become pregnant, or nursing.
Presence of psychotic features.
Unable to provide informed consent or comply with study procedures.
Previous treatment with riluzole.
Serious, unstable illnesses including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, hematologic disease, or HIV. This includes individuals with a history of COPD by diagnosis as well as persons taking inhalers for Asthma or Reactive Airway Disease.
Clinically significant abnormal levels (3x ULN or greater) of serum transaminases (ALT/SGPT; AST/SGOT), current or past blood dyscrasia.
Subjects with uncorrected hypothyroidism or hyperthyroidism.
DSM-IV alcohol or substance abuse or dependence within 90 days of the screening visit.
Treatment with a reversible MAOI, guanethidine, or guanadrel within 1 week, or any change in fluoxetine dosing within 8 weeks prior to visit 2. Use of antidepressant and sedative/hypnotic drugs at stable dose is permitted.
Documented history of hypersensitivity or intolerance to riluzole.
Subjects with a current or past history of other axis I disorders including schizophrenia, schizoaffective disorder, bipolar disorder or dementia. However, those with a co-morbid history of other Axis I disorder like major depression, dysthymia or other anxiety disorders will be included; the justification for this is that approximately 70% of subjects with PTSD have co-morbid depression and or alcohol abuse, and restricting the sample to PTSD patients without depression will not accurately reflect the scope of this disorder.
Patients who are currently at high risk for homicide or suicide, as indicated by an affirmative answer to the question: "In the last three months, have you attempted to kill yourself, made specific plans to kill yourself, or had the intention to kill yourself?"
Current or planned litigation regarding the traumatic event.
Patients who recently started trauma focused cognitive behavioral psychotherapy (Patient's underlying educational or supportive individual or group therapy will be included).
Patient's actively enrolled in an evidence based psychotherapy treatment (e.g., Cognitive Processing Therapy or Prolonged Exposure Therapy) will be excluded until that therapy has concluded, but may be re-approached at that time if patient self-report or clinician referral suggests persistent PTSD symptoms upon conclusion of that treatment.
Subjects with an artificial cardiac pacemaker or metallic implants within their body will be enrolled at WRNMMC for the placebo-control clinical trial portion of the study only. These individuals, due to their pre-existing medical condition, are medically ineligible to participate in the 1H MRS imaging portion of the study. Further, the Magnetic Resonance (MRI) Screening Form is use at WRNMMC will be used for participant screening prior to any imaging procedures.
Use of benzodiazepines.