Evaluation of Clonazepam and Paroxetine for Panic Disorder With Depression

INCLUSION CRITERIA: Patients with a primary diagnosis of Panic Disorder without Agoraphobia or Panic Disorder with Agoraphobia according to DSM-IV criteria, and co-morbid major depressive disorder are eligible. Patients are required to have a weekly panic attack frequency of greater than or equal to 1/ week in the month prior to intake or a CGI score greater than 4 in the week prior to randomization. Patients with co-morbid major depressive disorder will be included provided that the onset of PD was earlier than the onset of the depressive disorder. The presence of co-morbid depression will be determined by using DSM-IV criteria for major depressive disorder, and HDRS scores will be in the moderately-to-severely depressed range (greater than 15). Subjects will be at least 18 years old. Those above age 65 years must be able to tolerate paroxetine starting dose of at least 20 mg daily and be without hepatic or renal impairment. Male and female subjects will be included. The patient must have given written informed consent prior to any study procedures. In addition, eligible patients must be in good physical health as confirmed by a complete physical exam (including normal vital signs), electrocardiogram, neurological exam, and routine laboratory tests of blood and urine. Patients will be drug free for at least 7 days when starting with the study medication. We will study both, untreated, symptomatic patients, and patients who did not respond to their pervious psychopharmacological treatment. The unsuccessful medication will be tapered off, and a medication-free period of 7 days will be established. EXCLUSION CRITERIA: Patients with any serious or unstable medical disorder or condition that would preclude the administration of paroxetine or clonazepam (e.g. epilepsy, severe head injury, meningitis, allergic to either drug). Patients who would be unable to comply with study procedures or assessments. Patients who meet DSM-IV lifetime criteria for benzodiazepine abuse or dependence. Patients who are on other psychotropic drugs must have discontinued them for at least 1 week prior to randomization. Patients are ineligible who experience any current signs of symptoms of drug withdrawal during taper of unsuccessful medication. Patients who are currently at high risk for homicide or suicide. Patients who had previously failed an adequate trial of paroxetine or clonazepam. Women of childbearing potential who are not practicing a clinically accepted method of contraception or who have a positive pregnancy test or who are lactating. Patients who are currently treated with fluoxetine.