Research by psychopharmacology expert Dr. Anthony Rothschild funded by National Institutes of Mental Health

April 16, 2003

WORCESTER, Mass. - Psychotic depression is a major mental illness characterized by delusional thoughts and behaviors accompanying severe depression. Neither depression nor psychosis alone, psychotic depression (PD) is potentially fatal due to a high incidence of suicide amongst those who suffer from it - but is treatable with the right therapies. With the award of an unprecedented $1.5 million grant from the National Institutes of Mental Health (NIMH), renowned antidepressant drug expert and principal investigator Anthony Rothschild, MD, will compare two promising but unproven medication treatments for psychotic depression (PD) with a double-blind study, the gold standard for drug trials.

Approximately 15 to 19 per cent of patients suffering severe depression experience delusions which are typically less bizarre and subtler than those seen in chronic, major psychotic illnesses such as schizophrenia. Once the PD episode is treated, the delusions end. Despite the work of Dr. Rothschild and a handful of colleagues nationwide, however, the disorder continues to be under recognized, under diagnosed and, therefore, under treated.

“Psychotic depression is an ‘orphan illness’ in that no medications are currently FDA-approved for this diagnosis. While electro convulsive shock therapy is a good treatment, it is not for everyone and is not as readily accessible as medications. It is therefore important for us to explore treatment with medications,” explains Rothschild, the Irving S. and Betty Brudnick Professor of Psychiatry and director of clinical research in the Department of Psychiatry at the University of Massachusetts Medical School (UMMS).

The long-awaited clinical trial will compare the efficacy of the antipsychotic olanzapine (trade name Zyprexa) alone and in combination with the antidepressant sertraline (trade name Zoloft), and will further compare the response rates and side effects between older and younger PD patients. This collaborative four-site randomized controlled trial  (the other three sites are Cornell University in Westchester, New York, the University of Pittsburgh and the University of Toronto) is the first pharmacological treatment study of major depression associated with delusions to be funded by NIMH in over 20 years. The study, “Acute Pharmacotherapy of Psychotic Depression,” thus represents a major initiative for the NIMH, which several years ago had proposed studying the effects of a medication class called atypical antipsychotics for three illnesses, Alzheimer’s Disease, schizophrenia and psychotic depression; PD was later dropped from the study.

Undaunted, Rothschild and a handful of colleagues, some of whom are also principal investigators on the new study, continued to pursue funding and to research psychotic depression on their own. In 1992 Rothschild and Stanford University associate Alan F. Schatzberg, MD, published a paper in the American Journal of Psychiatry urging PD be separately identified as a distinct syndrome in the Diagnostic and Statistical Manual of Mental Disorders, the diagnostic authority for psychiatrists, to focus more attention on the disorder. Of the new, major NIMH funding, Rothschild says, “Persistence paid off. We’re very pleased!” All longstanding experts in PD, the study’s four investigators have developed a scientific protocol more rigorous than prior ones, which netted the renewed interest and funding from NIMH.

The protocol calls for subjects to take olanzapine either alone or in combination with sertraline for an initial 12-week acute phase. Those who respond completely with cessation of both depression and delusions will be asked to continue their medication for another 12-week stabilization phase. Those who respond only partially will have another medication added in the second 12 weeks, sertraline for those on olanzapine alone, and the mood stabilizer lithium for those already on olanzapine with sertraline. Subjects must be at least 18 years of age and do not need to have insurance to participate in the study. Interested patients and physicians can contact Colby Calkins at 508-856-1760, e-mail colby.calkins@umassmed.edu .

“We are excited by the opportunity our new study provides to identify easily accessible, well-tolerated pharmaceuticals that will improve outcomes for the thousands afflicted by psychotic depression,” says Rothschild, who has already been awarded numerous research grants to study the use of antidepressants in treating depressed patients, including the sexual dysfunction side effects of antidepressants. His work in this area found beneficial effects of “drug holidays” (discontinuing antidepressant use for 72 hours) on the sex lives of patients with depression. He also studies psychoneuroendicrinology, a burgeoning area of inquiry into the interface of endocrinology and psychiatry, recently publishing the comprehensive reference book Psychoneuroendocrinology: The Scientific Basis of Clinical Practice (American Psychiatric Press, 2003).

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research.  The Medical School attracts more than $143 million in research funding annually, 80 percent of which comes from federal funding sources.  Research funding enables UMMS scientists to explore human disease from the molecular level to large-scale clinical trials.  Basic and clinical research leads to new approaches for diagnosis, treatment and prevention of disease. Visit  www.umassmed.edu for additional information.

Contact: Sandra Gray, 508-856-2000