Research Examining Gulf War Illness in Our Nations Service Members (REGIONS)

Inclusion Criteria:

• Living in Central Texas near Killeen, Austin, Temple or Waco
• Served on active military duty and deployed to the Persian Gulf region for some period between August 1990 & July 1991
• English speaking and able to understand the consent form and study questionnaires
• Willing to be randomized to treatment and participate in 1-month follow up
• men & women between the ages of 43 to 70
• meet Kansas GWI case definition for the diagnosis of GWI
• report a baseline score > 4 on a 10-point Pain Visual Analog Scale (VAS)
• female participants of childbearing potential must test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control (for example, oral contraceptives or Norplant; a reliable barrier method of birth control [diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam); intrauterine devices; partner with vasectomy; or abstinence) during the study and for 2 months following the last dose of the study drug. [Note that this inclusion criterion applies only to females of childbearing potential. Females of childbearing potential are defined as women not surgically sterilized and between menarche and 2 years post-menopause.]

Exclusion Criteria:

• Unstable or poorly controlled chronic medical illness such as Diabetes type-II, Hypertension (HTN), heart disease, endocrine disorders, narrow angle glaucoma
• Significant Central Nervous System disease including transient ischemic attacks (TIAs) or stroke, Dementia, syncopal episodes, severe head trauma, multiple sclerosis
• Serious or advanced heart disease or clinically relevant abnormal electrocardiogram (ECG), postural hypotension
• Untreated sleep apnea or body mass index placing patients at risk for undiagnosed sleep apnea (BMI> 35 kg/m2)
• Diabetes type-I and patients with Diabetes type-II associated with peripheral neuropathy, hepatitis, liver failure/cirrhosis
• End stage renal disease
• History of hypersensitivity reaction to pregabalin, duloxetine, venlafaxine; active treatment with duloxetine or pregabalin; History of failure of duloxetine or pregabalin at therapeutic doses; history of angioedema reaction to pregabalin
• Active systemic infectious disease such as tuberculosis and HIV, shingles
• Autoimmune mediated illnesses such as systemic lupus erythematosis, rheumatoid arthritis, scleroderma
• History of mental illness requiring hospitalization (depression, bipolar illness, post traumatic stress disorder, history of suicide attempts, psychosis, schizophrenia spectrum); Current major depression of dysthymia; patients lacking capacity to make medical decisions
• Use of monoamine oxidase inhibitors (MAOIs) within 2 weeks of evaluation; Active ongoing use of the following agents: desvenlafaxine, fenfluramine, linezolid, milnacipran, phentermine, tryptophan, tramadol, opiates
• Current (meets criterion within the last 6 months) for drug or alcohol dependence (except for nicotine and caffeine)
• Cancer other than non-melanoma skin cancers
• Women who are pregnant or desire to become pregnant, breastfeeding, who use unreliable contraception methods
• Those with occupations requiring use and/or operation of hazardous heavy equipment or professional drivers
• Patients for whom the potential risk outweighs the potential benefit in the opinion of the treating psychiatrist