Search

Context Extracts of Hypericum perforatum (St John's wort) are widely used for the treatment of depression of varying severity. Their efficacy in major depressive disorder, however, has not been conclusively demonstrated. Objective To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder. Design and setting Double-blind, randomized, placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States. Participants Adult outpatients (n = 340) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale (HAM-D) of at least 20. Interventions Patients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. Based on clinical response, the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg. Responders at week 8 could continue blinded treatment for another 18 weeks. Main outcome measures Change in the HAM-D total score from baseline to 8 weeks; rates of full response, determined by the HAM-D and Clinical Global Impressions (CGI) scores. Results On the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. The random regression parameter estimate for mean (SE) change in HAM-D total score from baseline to week 8 (with a greater decline indicating more improvement) was -9.20 (0.67) (95% confidence interval [CI], -10.51 to -7.89) for placebo vs -8.68 (0.68) (95% CI, -10.01 to -7.35) for H perforatum (P =.59) and -10.53 (0.72) (95% CI, -11.94 to -9.12) for sertraline (P =.18). Full response occurred in 31.9% of the placebo-treated patients vs 23.9% of the H perforatum-treated patients (P =.21) and 24.8% of sertraline-treated patients (P =.26). Sertraline was better than placebo on the CGI improvement scale (P =.02), which was a secondary measure in this study. Adverse-effect profiles for H perforatum and sertraline differed relative to placebo. Conclusion This study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy.

This the Diagnostic Interview for Genetic Studies (DIGS), a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions. The DIGS, which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health (NIMH) Genetics Initiative, has the following additional features: (1) polydiagnostic capacity; (2) a detailed assessment of the course of the illness, chronology of psychotic and mood syndromes, and comorbidity; (3) additional phenomenologic assessments of symptoms; and (4) algorithmic scoring capability. The DIGS is designed to be employed by interviewers who exercise significant clinical judgment and who summarize information in narrative form as well as in ratings. A two-phase test-retest (within-site, between-site) reliability study was carried out for DSM-III-R criteria—based major depression, bipolar disorder, schizophrenia, and schizoaffective disorder. Reliabilities using algorithms were excellent (0.73 to 0.95), except for schizoaffective disorder, for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability. A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions. The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders, schizophrenia, and related conditions.

In Reply.— Dr Prakash is correct in his statement that the HDS was originally developed to measure change in depressive symptoms among patients who had already received the diagnosis of depression. However, the scale has been widely used as a diagnostic aid, with a range of cutoff scores used to define patient groups. Thus, our use, as indicated in the original article, is not without some scientific precedent. Further, in agreement with Dr Prakash, we recognize that the HDS may not be the best measure of depressive symptoms in schizophrenic patients. For this reason, we also examined ratings of depressive mood obtained from the Brief Psychiatric Rating Scale and looked at HDS scores, deleting items such as work and activities that might have been affected by schizophrenic deficits rather than specific depressive features. Results with these measures were congruent with those obtained with the HDS. The many variations of the HDS are

• Data were collected during a year-long multicenter collaborative trial comparing short-acting fluphenazine hydrochloride with long-acting fluphenazine decanoate in a group of schizophrenic patients being maintained in the community. We examined the emergence and course of depressive symptomatology, operationally defined by the Hamilton Depression Scale total score. Of 211 patients, approximately 25% had depression develop within five months after discharge. Depressed patients had a more chronic psychiatric history and, contrary to the hypothesis that depression is a favorable prognostic indicator, they were more likely to relapse. There were no differences in incidence of emergent depression between the two drug treatment groups.

We tested the role of guaranteed delivery of medication in the prevention of relapse and the enhancement of adjustment in the community in patients with schizophrenia. Two hundred and ninety newly hospitalized patients at four hospitals were randomly assigned to groups receiving either long-acting injectable fluphenazine decanoate or short-acting oral fluphenazine hydrochloride. After discharge and stabilization, patients were treated in the community for up to one year. By the end of the year, 28% of all the patients had relapsed. Contrary to hypothesis, differences between the two treatment groups in relapse percentages were not significant. Furthermore, there were no differences between the treatment groups as to development of affective symptomatology or social adjustment. Patients who rated themselves as having more symptom distress at the start of the community-maintenance phase of the study relapsed much earlier while receiving fluphenazine decanoate rather than fluphenazine hydrochloride. The results suggest that compliance is not an important determinant of relapse among newly discharged schizophrenic patients.