Minocycline for Treatment of Posttraumatic Stress Disorder in Veterans

Inclusion Criteria

• Veterans between the ages of 19 and 65 who meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for chronic PTSD.
• Patients who have been taking an adequate dose of selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) medication, bupropion, or mirtazapine for a minimum of 8 weeks at the time of study entry.
• PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5) score of > 33 at the Screening Visit. Eligible persons will be allowed to have other symptoms that are commonly comorbid with PTSD (e.g., anxiety, somatic symptoms). This strategy will provide a feasible and generalizable sample of those with chronic PTSD.

Exclusion Criteria

• Patients with a concurrent DSM-5 diagnosis in any of the following categories:

1.1. Major Neurocognitive Disorder (NCD) 1.2. Lifetime Schizophrenia and other Psychotic Disorders 1.3. Lifetime Bipolar Disorder 1.4. Alcohol Dependence or Abuse in 3 months prior to the Screening Visit 1.5. Any other Substance Dependence or Abuse (excluding nicotine) in 12 months prior to the Screening Visit 1.6. Any other concurrent Axis I Disorder (including Major Depressive Disorder) must be secondary to the primary diagnosis of PTSD.

• Chronic pain levels requiring use of any opiate medications with the exception of Tramadol. Patients are allowed the use of Tramadol at 25-50 mg per day dosing.
• Any condition or disorder that may cause neuropsychiatric sequelae (e.g., Parkinson's disease, stroke, seizures, or TBI).
• Past chronic PTSD, meaning PTSD that preceded the incident traumatic event responsible for the current PTSD. Other traumatic life events will not be exclusionary unless they resulted in previous PTSD.
• Patients with a history of intolerance or hypersensitivity to minocycline or other tetracycline antibiotics, or prior tetracycline use 2 months prior to the Screening Visit.
• Concomitant treatment with penicillin or other antibiotics, or treatment with antibiotics for greater than 7 days in the past month.
• Use of aspirin, non-steroidal anti-inflammatory agents (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors for < 6 months prior to study entry or dose changes after study entry. Limited as-needed use is permitted prior to study entry but not during the study.
• Use of statins will not be permitted during the study as they have been shown to reduce levels of pro-inflammatory cytokines.
• Use of concomitant anti-coagulant drugs (except low-dose aspirin) as minocycline has been shown to depress plasma prothrombin activity.
• Any degree of hepatic or renal failure that in the Investigator's judgement would pose a safety risk for treatment with minocycline.
• Conditions which may be negatively affected by minocycline treatment, such as active inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease).
• A history of C. difficile colitis.
• Patients who based on history or mental status examination have a significant risk of committing suicide, or who are homicidal or violent and who are in the Investigator's opinion in significant imminent risk of hurting others.
• Patients who have a medical condition that, in the Investigator's opinion, would expose them to an increased risk of a significant adverse event or interfere with assessments of safety and efficacy during the course of the trial.
• Women who are pregnant or plan to become pregnant during the study. All women of childbearing potential must have a negative urine pregnancy test at the Screening Visit and throughout the study. Sexually active women participating in the study must use a medically acceptable form of contraception.
• Patients with a current known infection or who are acutely ill.
• Patients with an autoimmune disease (i.e., Lupus, Rheumatoid Arthritis).
• Immunocompromised patients (i.e., HIV).
• Patients with thyroid disorders unless euth