Drug Treatment Validation of Functional Magnetic Resonance Imaging in Generalized Anxiety Disorder
Condition: Generalized Anxiety Disorder
MeSH terms: Anxiety Disorders
Intervention: Alprazolam (Xanax); Placebo
Intervention description: Drug dose will be fixed across patients: alprazolam 0.5 mg b.i.d escalating to 1.0 mg b.i.d. The treatment duration will be approximately 28 days (4 weeks).; Placebo, bid, p.o. for 28 +/- 2 days.
Intervention MeSH terms: Alprazolam
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Anxiety disorders; Generalized anxiety

Summary:

      The purpose of this study is to find out how an anti-anxiety drug or placebo affects the
      activity of your brain when you are at rest and when you are viewing emotional material, such
      as, emotional faces and pictures.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female between 18 - 65 years of age, inclusive

          2. In good general health (as determined by medical history, physical examination,
             laboratory assessments and electrocardiogram (ECG)), especially no findings (including
             concomitant medications) that would constitute contraindications for treatment with
             alprazolam

          3. Diagnostic and Statistical Manual-IV criteria for Generalized Anxiety Disorder (GAD)
             (exception: at least 3 months of symptoms)

          4. Hamilton Anxiety Scale at screening >/= 20

          5. Montgomery-Asberg Depression Rating Scale (MADRS) at screening < 25

          6. Prior medications washout:

               -  2-week medication washout prior to randomization for most psychotropic
                  medications

               -  If prior history of fluoxetine use, this drug must have been discontinued at
                  least 5 weeks before randomization

          7. For females of non-childbearing potential: either postmenopausal for the past year
             (confirmed by an follicle stimulating hormone level greater than 40 mIU/mL unless the
             subject is receiving hormone replacement therapy), or surgically sterile (e.g., tubal
             ligation, hysterectomy)

          8. Males and female subjects of child-bearing potential may be included if using
             appropriate contraceptive methods:

               -  must use abstinence or two methods of contraception throughout the trial:

                    -  should include one primary (e.g., systemic hormonal contraception, vasectomy
                       of the male partner) AND one secondary barrier method (e.g., latex condoms,
                       spermicide) OR

                    -  a double barrier method (e.g., latex condom plus spermicide (foam,
                       suppository, gel, cream)) may be used

          9. GAD should be the clinically predominant disorder, as judged by the investigator,
             considering relative severity and impact on functioning

        Exclusion Criteria:

          1. Axis I disorder other than stated above with the exception of the following permitted
             comorbidities:

               -  history of (within past 6 months) or current dysthymia

               -  current (within past 6 months) depressive episode with MADRS at baseline < 25

               -  history of major depression as long as no current depressive episode as defined
                  above

          2. Drug or alcohol dependence in the past 6 months

          3. Positive urine toxicology (drugs of abuse as determined by clinician's assessment of
             positive urine test)

          4. Active suicidal ideation (determined by clinician)

          5. For females of childbearing potential: Pregnancy or intent to become pregnant or
             currently breastfeeding

          6. Current use of beta-blockers or stimulants (e.g., Methylphenidate, d-Amphetamine,
             modafinil, and illicit drugs like cocaine or 3,4-methylenedioxy-N-methylamphetamine
             [MDMA])

          7. Current regular use of antihistamines (except for inhalants which are permitted)

          8. Current use of herbal medication for mood or anxiety disorders and unwillingness to
             discontinue use for the duration of the study

          9. Current use of fluoxetine

         10. Concomitant psychotropic medications including regular use of sleeping medications
             (also herbals)

               -  occasional use of sleeping medication, with the exception of benzodiazepines, is
                  permitted as long as it is not taken the evening prior to a visit

         11. Past intolerance (including allergic) to, or clear history of non-response to the
             study medication

         12. Current smoker (> 10 cigarettes/day); habitual caffeine consumption of more than 400
             mg/d (approximately 4 cups of coffee or equivalent)

         13. Body mass index > 32.5 kg/m2

         14. Contraindication to magnetic resonance imaging based on a standard fMRI screening
             forms

         15. Concurrent participation in an institutional review board (IRB) approved
             investigational drug trial

         16. Any other reason why, per clinician, the patient should not participate in this study
             (to be included in this assessment are all considerations, warnings, precautions as
             per current FDA-approved drug label for Xanax®)