Baseline profiles were derived from the HSCL-90 self-rating scale, and the SUMMY variables for this sample were first compared with the same baseline measures derived from the first 80 Pisa Center subjects enrolled in the Worldwide Upjohn Phase II Study for Panic Disorder (9). The Upjohn study patients were selected utilizing stricter criteria in two respects, compared with the CLO-IMI study; the Upjohn study required at least one panic attack each week during the month before evaluation, whereas the CLO-IMI study required panic attacks during the past month without specifying disorder, or other anxiety disorder, whereas the CLO-IMI study did not. Even though the 152 subjects participating in the IMI or CLO treatments were selected according to broader, less restrictive criteria, they did not differ significantly from the Upjohn sample in any of the major SUMMY variables (Table 2). Contrary to expectation, the depressive mood item from the HDS was not significantly higher in the more leniently selected open study sample. Obviously, owing to selection criteria, the Upjohn study patients would be ex­pected to have more spontaneous and situational panic attacks, but even these differences were small and nonsignificant. The variance in monthly number of situational panic attacks was higher in the Upjohn sample (p < 0.05), indicating
that relatively few cases accounted for the mean difference of two attacks per month between the two samples. The open study patients had slightly higher ratings on phobic avoidance, anticipatory and baseline anxiety, and impaired social adjustment (i.e., greater disability). A comparative analysis of the HSCL-90 factors also confirmed nearly super-imposable psychopathological profiles for the two groups (Table 2). The open study sample was slightly to somewhat higher in mean scores on all the psycho-pathology factors, but only the obsessive-compulsive factor mean was significantly higher, whereas the depression factor was nearly so. The actual rank ordering of the 9 HSCL factors by their weighted mean item scores was practically identical for the two samples. These baseline comparisons of the two study samples suggest a particular stability of the panic-phobic diagnostic categories. Although the operational cri­teria for the disorders were less strictly followed in the open trial, the typical panic-phobic syndromes are clearly present in that sample, and the overall profiles of psychopathology are remarkably similar. In the CLO-IMI study, the two treatment groups were comparable in the proportion of the three DSM-III-R diagnoses and in age, sex, and age at onset. These characteristics were also not related to dropout rates. The attrition rate to date has included 31 IMI and 29 CLO patients. None of these cases returned after the first visit and then were lost to follow-up. The attrition rate did not differ for the two groups, but patients lost from the IMI group had significantly more situational panic attacks per month than those who discontinued CLO treatment (Table 3). Dropouts from the two treatments did not differ significantly in the other syndrome features shown in Tables 3 and 4. At present 33 patients are in progress in the study but have completed less than 10 weeks of treatment. The 33 IMI and 26 CLO cases who have completed the 10th week did not differ significantly at baseline in any of the major features shown in Table 3. (more…)

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. (more…)

This study was planned and performed with the aim of monitoring system­atically both patient characteristics and the outcome of different treatment mo­dalities under routine clinical practice conditions. Based on previous reports and personal clinical experiences, a generally accepted standard treatment with IMI and a promising but less widely tried treatment with CLO, both in flexible dosages, were compared. The design allowed for baseline assessment and long-term routine monitoring of treatment response in a large sample of subjects with panic disorder. The advantages over other clinical reports are the random assignment of drugs, the systematic assessment using standardized rating scales and the opportunity to compare this sample of patients with a previously collected sample that was used in a general clinical trial by the same group. The 152 patients selected for the IMI-CLO study to date by a broad interpre­tation and application of DSM-III-R criteria differed surprisingly little from 80 other patients with panic disorder, selected by the same research group, according to more strict diagnostic criteria for a worldwide multicenter study of panic disorder. The demographic and psychopathological characteristics of the two groups widely overlapped. No significant differences were found in age, sex, number of spontaneous and situational panic attacks, percentage of time antic­ipatory anxiety distressed the patients, level of phobic avoidance, depressive mood (HDS) or social disability. In addition, these findings were confirmed by patients’ self-evaluations. The two groups did not differ at baseline on the HSCL factors of anxiety, phobic anxiety, or somatization. The CLO-IMI sample was significantly higher on the obsessive-compulsive factor, and their depression self-ratings were nearly significantly higher. The rank ordering of scores on the HSCL 9-factor profile was practically identical for the two samples, although the general profile level was somewhat higher for the CLO-IMI sample. These observations need further study. Panic disorders appeared to be sharply defined in both groups by profiles with greatest elevations on the anxiety, phobic anxiety, and somatization factors. Even though we included almost the whole spectrum of patients with panic attacks, including multiple diagnoses in axis one, the major clinical features of the CLO-IMI sample did not differ significantly from the typical symptomato-logical picture of panic disorder as presented by the Pisa subsample of what is probably the most carefully selected sample of panic disorder ever undertaken. This evidence supports the homogeneity, reliability, and stability of the panic disorder diagnosis across various patient samples and clinicians, and observa­tion times. The diagnostic subdivision of panic disorder according to DSM-III-R is based essentially on different degrees of phobic avoidance (none, limited, extreme). These diagnostic subtypes did not relate to different rates of drug response to IMI or CLO. This finding supports a more unitarian nosological conceptualiza­tion of panic disorder. Clinical response and side effects have not differed appreciably between the IMI and CLO groups. At similar dosages, both drugs appeared equally effective on the overall symptomatology of panic disorder and agoraphobia. Significant advantages for CLO were found on clinicians’ ratings of the psychic and somatic anxiety items from the HDS. On the former, CLO had faster action with an advantage at 2 weeks, but at 6 and 10 weeks, CLO and IMI were comparable. The CLO advantage on somatic anxiety was apparent at weeks 2 through 10. Since this evidence for treatment differences is relatively limited in view of the number of statistics applied, we prefer not to overinterpret it at this time. An important implication of our findings may be that CLO’s more predominantly serotonin-inhibiting effect does not seem to determine a different spectrum of activity in panic disorder. These data do not clearly support or indicate whether the panic attacks were blocked before the anticipatory anxiety and avoidance behavior decreased. A trend was noticed in favor of a better response of CLO on situational attacks, anticipatory anxiety, and phobic avoidance. Subsequent analyses of all data from the entire sample when the study is completed should better clarify these latter points.

Next post about Depression Treatment will be 1 February. Sorry to all readers…

Psychiatric Clinic, University of Pisa, 56100 Pisa, Italy; "Department of Psychology, Boston University, Boston, Massachusetts 02215
Although the efficacy of imipramine (IMI), phenelzine, and alprazolam in the treatment of panic disorder is well established (7,8,11-15), the usefulness of other members of the same drug classes remains to be proved. One aim of this comparative study was to ascertain whether a tricyclic antidepressant (TCA) with predominantly serotoninergic effects, such as clomipramine (CLO), had a different antipanic action from IMI. After more than 30 years as a standard comparative compound for clinical drug trials of antidepressants, IMI is currently the most widely used TCA for panic disorder. Although no drug has yet obtained an official antipanic indication in the United States, IMI has become the unofficial standard for comparison. In the last few years, several clinical studies have suggested that CLO also may be effective in the treatment of panic-agoraphobic disorders (2,4,5,10). Most of these were open and uncontrolled clinical trials that used CLO dosages lower than IMI. Other anecdotal information from personal communications with academic investigators supported these open trial findings. Moreover, CLO had been employed by us in the prior treatment of a group of panic-agoraphobic disorders, and we used comparable CLO and IMI dosages. Our findings were consistent with the reports cited in indicating CLO efficacy. Based on our findings and the other reports, we began to employ routinely both CLO and IMI as pharmacotherapies for panic-agoraphobic disorders en­countered in our clinical practice. We decided to randomly assign the drugs to patients with panic attacks used in our more formal double-blind clinical trials. As phenelzine is not available on the Italian market and alprazolam has become available only very recently, IMI and CLO were the two drug therapies most widely used in our practice. The CLO versus IMI study is still in progress, and this article reports a preliminary analysis of the findings to date. (more…)

1. American Psychiatric Association. (1985): DSM-IH-R in Development. American Psychiatric Association, Washington, D.C. 2. Caetano, D. (1985): Treatment for panic disorders with Clomipramine. J. Brasil. Psiguiat., 34(2): 123-132. 3. Derogatis, L. R., Lipman, R. S., and Rickels, K. (1973): The Hopkins Symptoms Checklist (HSCL): A measure of primary symptoms dimensions in psychological measurement. In: Modern Problems in Pharmacopsychiatry, edited by P. Pichot. Karger, Basel, Switzerland. 4. Gloger, S., Grunhaus, L., Birmacher, В ., and Troudart, T. (1981): Treatment of spontaneous panic attacks with clomipramine. Am. J. Psychiatry, 138:1215-1217. 5. Grunhaus, L., Gloger, S., and Birmacher, B. (1984): Clomipramine treatment for panic attacks in patients with mitral valve prolapse. J. Clin. Psychiatry, 45:25-27. 6. Hamilton, M. (1960): A rating scale for depression. / Neurol. Neurosurg. Psychiatry, 23:56-62. 7. Klein, D. F. (1967): Delineation of two drug responsive anxiety syndromes. Psychopharmacology, 5:397-406. 8. Klein, D. F., and Fink, M. (1967): Psychiatric reaction patterns to imipramine. Am. J. Psychiatry, 119:432. 9. Klerman, G. L., Coleman, J. H., and Purpura, R. P. (1986): The design and conduct of the Upjohn Cross-National Collaborative Panic Study. Psychopharmacol. Bull, 22(l):59-64. 10. Pecknold, J. C, McLure, U. J., Appeltauer, L., Allan, Т ., and Wazesinski, L. (1982): Does tryptophan potentiate Clomipramine in the treatment of agoraphobic and social phobic patients? Br. J. Psychiatry, 140:484-490. 11. Rizlev, R., Kahn, R. J., McNair, D. M., and Frankenthaler, L. M. (1986): A comparison of alprazolam and imipramine in the treatment of agoraphobia and panic disorder. Psychopharmacol. Bull, 22(1):167-172. 12. Sargant, W., and Dally, P. (1962): Treatment of anxiety states by antidepressant drugs. Br. Med. J., 1:6-9. 13. Sheehan, D. V., Ballenger, J., and Jacobsen, G. (1980): Treatment of endogenous anxiety with phobic, hysterical, and hypochondriacal symptoms. Arch. Gen. Psychiatry, 37:51-59. 14. Zitrin, C, Klein, D. F., and Woerner, M. (1978): Behavioral therapy, supportive psychotherapy, imipramine and phobias. Arch. Gen. Psychiatry, 35:307-316. 15. Zitrin, C, Klein, D. F., and Woerner, M. (1980): Treatment of agoraphobia with exposure in vivo and imipramine. Arch. Gen. Psychiatry, 37:63-72.
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