Intervention: Alprazolam
Trial phase: Phase 4
ATC code: N05BA12
SMILES: Cc1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1)=NC2
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 21
Group description: Alprazolam, an FDA-approved drug, will be administered to 24 patients with generalized anxiety disorder.

Alprazolam (Xanax): 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).
Eligibility criteria:
Inclusion Criteria:

Male or female between 18 - 65 years of age, inclusive
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
Diagnostic and Statistical Manual-IV criteria for Generalized Anxiety Disorder (GAD) (exception: at least 3 months of symptoms)
Hamilton Anxiety Scale at screening >/= 20
Montgomery-Asberg Depression Rating Scale (MADRS) at screening < 25

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
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)

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
GAD should be the clinically predominant disorder, as judged by the investigator, considering relative severity and impact on functioning

Exclusion Criteria:

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
Drug or alcohol dependence in the past 6 months
Positive urine toxicology (drugs of abuse as determined by clinician's assessment of positive urine test)
Active suicidal ideation (determined by clinician)
For females of childbearing potential: Pregnancy or intent to become pregnant or currently breastfeeding
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])
Current regular use of antihistamines (except for inhalants which are permitted)
Current use of herbal medication for mood or anxiety disorders and unwillingness to discontinue use for the duration of the study
Current use of fluoxetine

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
Past intolerance (including allergic) to, or clear history of non-response to the study medication
Current smoker (> 10 cigarettes/day); habitual caffeine consumption of more than 400 mg/d (approximately 4 cups of coffee or equivalent)
Body mass index > 32.5 kg/m2
Contraindication to magnetic resonance imaging based on a standard fMRI screening forms
Concurrent participation in an institutional review board (IRB) approved investigational drug trial
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®)