MATERIAL AND METHOD
Subjects
A total of 152 psychiatric outpatients have been accepted and randomly assigned to treatments. Their mean age was 38, and mean age at onset of the disorder was 28. Male-to-female ratio was 41%-to-59%. Other sample characteristics are shown in Table 1.
Procedure
The diagnosis was made by the DSM-III-R (1) criteria for panic disorder, panic disorder with limited phobic avoidance, and panic disorder with extensive phobic avoidance. Comorbidity of panic disorder with personality disorder was not an exclusive criterion.
Each patient was seen at each visit by a senior and a junior psychiatrist. The latter evaluated the patient on a set of rating instruments. The psychiatrist measures referred to in this report included: (a) Panic Disorder Questionnaire, a Pisa research group instrument that provided diagnostic information; (b) Adult Personal Data Inventory for demographic, clinical, personal, and family history; (c) Clinical Global Index (CGI), well-known scales for rating improvement and severity of illness; (d) Panic and Anticipatory Anxiety Scales, which provided data about the frequency of panic attacks and pervasiveness of anticipatory anxiety; (e) Phobia Scale, a 10-point scale of extensiveness of phobic avoidance behavior; (f) Hamilton Depression Scale (HDS), for this report we used the ratings on the Depressive Mood, Psychic Anxiety, Somatic Anxiety, and Hypochondriasis items (6); (g) Sheehan Clinician Rated Anxiety Scale; and (h) DOTES, a widely used measure of side effects. The first two measures were obtained only at baseline, and the others were assessed at each visit. In addition to the psychiatrist measures, patients completed the 90-item Hopkins Symptom Checklist (HSCL) (3) at each visit. After baseline, subsequent evaluations were performed after 2 weeks and at monthly intervals. A summary data sheet (SUMMY) of important characteristics and scores on some major variables was prepared at each evaluation to facilitate rapid preliminary evaluation of results on personal computers. The SUMMY variables were: age, sex, diagnosis, pharmacological dosages, severity of side effects, number of major spontaneous and situational panic attacks during the last month, percentage of time spent in anticipatory anxiety in the past month, severity of phobic avoidance, depressed mood, psychic anxiety, somatic anxiety, hypochondria, severity of social disability, global improvement, and severity of the illness. For the present report, data analyses were performed on the first 59 patients who continued the medication according to protocol and completed at least 10 weeks of treatment. Although the study was conducted in general as simple, naturalistic, open treatment, the patients were randomly assigned to CLO or IMI, at dosages ranging from 25 to 300 mg. Dosages were progressively increased according to clinical judgment. The mean dosage was 143.6 mg for IMI and 127.9 mg for CLO, and the difference was not significant. The study plan also includes gradual drug dosage reduction, beginning after about 2 months of optimal response, and withdrawal is not to occur before the 8th month of treatment. Periodic standard assessments of patients are to continue bimonthly until 2 years after baseline. Informed consent was obtained from patients, and patients and relatives were given a brochure with a detailed and simple description of the disorder. Patients were requested to telephone the junior psychiatrist any time they needed help during the day. At treatment visits after baseline, patients were also provided with psychotherapeutic support, which included cognitive and behavioral therapy guidelines. The latter was offered mostly after panic attacks had subsided with pharmacological treatment.