OBJECTIVES: I. Determine whether the benzodiazepine alprazolam reinforces self-medication behavior in anxious patients with varying histories of using other drugs.

II. Establish outpatient methods for the study of self-medication and drug reinforcement in patients vulnerable to prescription drug abuse or dependence.

III. Evaluate the influence of alcohol and other non-prescription drug use as determinants of vulnerability in these patients.

IV. Identify personality, attitudinal, or other variables that might predict different patterns of self-medication.

V. Assess the effects of cognitive-behavioral therapy on alprazolam self-medication.

PROTOCOL OUTLINE: This protocol involves different experiments examining self-medication with anxiolytic medications in selected patients, and cognitive-behavioral therapy for anxiety. Capsules are color coded and taken under double-blind conditions. Compliance is monitored with the Medication Event Monitoring System, which automatically registers the date and time each bottle is opened.

The physician directs therapy administration, using some combination of the following: blind choice test, antianxiety agent(s), placebo, and cognitive-behavioral therapy.

• Anxiety Disorder
• Panic Disorder

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Primary diagnosis of generalized anxiety or panic disorder Determined by Structured Clinical Interview for DSM IV
• Hamilton Anxiety Scale (HAM-A) score at least 14 AND Profile of Mood States (POMS) tension/anxiety scale score at least 20
• Concurrent diagnoses allowed: Mild to moderate agoraphobia Simple or social phobias Secondary unipolar affective disorders
• No current substance abuse, dependence, or substance abuse treatment Drug-free urine sample required
• No history of other primary Axis I diagnosis other than tobacco dependence

--Prior/Concurrent Therapy--

• No prior formalized non-drug therapy for anxiety disorder
• No concurrent prescription psychoactive medication
• No history of benzodiazepine dependence

--Patient Characteristics--

• Age: 18 to 50
• Other: Medically healthy Negative pregnancy test required No occupational requirement to work in hazardous situations