An overview of recent findings of the Stanley Foundation Bipolar Network (Part I).

AIM AND METHODS: Selected recent findings of the Stanley Foundation Bipolar Network are briefly reviewed and their clinical implications discussed. RESULTS: Daily prospective ratings on the NIMH-LCM indicate a high degree of residual depressive morbidity (three times that of hypomania or mania) despite active psychopharmacological treatment with a variety of modalities including mood stabilizers, antidepressants, and benzodiazepines, as well as antipsychotics as necessary. The rates of switching into brief to full hypomania or mania during the use of antidepressants is described, and new data suggesting the potential utility of continuing antidepressants in the small group of patients showing an initial acute and persistent response is noted. Bipolar patients with a history of major environmental adversities in childhood have a more severe course of illness and an increased incidence of suicide attempts compared with those without. Preliminary open data suggest useful antidepressant effects of the atypical antipsychotic quetiapine, while a double-blind randomized controlled study failed to show efficacy of omega-3 fatty acids (6 g of eicosapentaenoic acid compared with placebo for 4 months) in the treatment of either acute depression or rapid cycling. The high prevalence of overweight and increased incidence of antithyroid antibodies in patients with bipolar illness is highlighted. CONCLUSIONS: Together, these findings suggest a very high degree of comorbidity and treatment resistance in outpatients with bipolar illness treated in academic settings and the need to develop not only new treatment approaches, but also much earlier illness recognition, diagnosis, and intervention in an attempt to reverse or prevent this illness burden.

Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.

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.