First Large-Scale Study Addressing Augmentation
Treatment For Resistant Major Depressive Disorder
August 28, 2006
In the first large-scale study of its kind, researchers at Cedars-Sinai found
that people suffering from resistant major depressive disorder who don't respond
to standard antidepressants can benefit when the drug therapy is augmented by a
broad spectrum psychotropic agent, even when treated for a brief period of time.
The study led by Mark Hyman Rapaport, M.D., chair of the department of
psychiatry at Cedars-Sinai, was recently published in Neuropsychopharmacology
AOP.
Although physicians have used a two-pronged drug therapy approach to boost the
effectiveness of antidepressants in depressed patients who show resistance to
the standard SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants such
as Prozac and Zoloft, this is the first time continuation of supplementary
treatment was studied in severely ill individuals.
The study, which tracked a group of depressed patients who showed resistance to
the standard SSRI antidepressant therapy found that those characterized as less
severely ill only needed to stay on the broad spectrum psychotropic agent
Risperidone for a brief period of time to experience lasting benefits; making
their antidepressant medication work effectively. Those depressed patients who
were characterized as more severely ill, however, needed to continue Risperidone
on an ongoing basis to experience the same level of effectiveness.
Approximately 40 percent of people who suffer from depression cannot get better
with the use of antidepressants or psychotherapy. Their inability to improve can
cause problems with many aspects of their lives, including work and family
relationships, and can become expensive to treat.
“The implications of our research shows that a certain subset of individuals
with chronic depression who don't respond to standard treatment with
antidepressant medication could benefit from a brief period of supplementary
therapy,” said Dr. Rapaport, the study's principal investigator.
“This type of adjunctive treatment is likened to how a patient with a severe
autoimmune disease who is on anti-inflammatory medication is given a steroid to
quiet his/her symptoms when they flare up,” Rapaport continued. “Typically,
these patients don't need to stay on the steroid indefinitely for it to be
effective in the long-term.”
Patients with major depressive disorder who did not respond to at least one
pharmacological treatment for major depression participated in the study. On
average, the majority of patients had not responded to more than two
medications, and the mean length of illness had been almost two years.
Subjects were treated with Citalopram, up to 60 milligrams per day for four to
six weeks. Those who did not have at least a 50 percent reduction in symptoms
were offered the opportunity to have unblinded standard treatment with a broad
spectrum psychotropic agent (atypical antipsychotic) Risperidone at up to 2
milligrams per day.
The majority of individuals participated in this phase during which both
researchers and patients were aware of the drug and dosage, and almost 60
percent of people who had Risperidone augmentation met criteria for being in
remission from depression by the end of four to six weeks of this treatment. At
that point, individuals entered a double-blind portion of the protocol where
Risperidone was either continued or the patient was placed on a placebo.
“We are very encouraged by this research. Treatment-resistant depression is
associated with the grave risk of increased morbidity and mortality and with a
severely decreased quality of life. It is one of the most pressing public health
needs that we face as a society,” Rapaport said. “We hope this study will
stimulate other researchers to pursue investigating the need for continuation of
supplemented therapies.” Major depressive disorder, characterized by sadness,
sleeplessness, fatigue, feelings of worthlessness, and other debilitating
symptoms is the world's most silent public health disorder. Depression among
18-45 year-olds is the leading cause of disability worldwide. The presence of
depression increases one's risk for heart attack, stroke, and can cause diabetes
to worsen. In addition, depression increases one's risk of suicide; almost twice
as many people die from suicide than homicide in the United States.
The abstract of the study Effects of Risperidone Augmentation in Patients with
Treatment-Resistant Depression: Results of Open-Label Treatment Followed by
Double-Blind Continuation, can be accessed on the Neuropsychopharmacology
website:
http://www.nature.com/npp/journal/vaop/ncurrent/abs/1301113a.html
Dr. Mark Hyman Rapaport was the study's principal investigator. Co-principal
investigators were Charles B. Nemeroff, Ph.D., M.D. and Martin B. Keller, M.D.
The research was funded by Janssen Pharmaceutica, and by a Cedars-Sinai grant.
The first of seven hospitals in California whose nurses have been honored with
the prestigious Magnet designation, Cedars-Sinai Medical Center is one of the
largest nonprofit academic medical centers in the Western United States. For 18
consecutive years, it has been named Los Angeles' most preferred hospital for
all health needs in an independent survey of area residents. Cedars-Sinai is
internationally renowned for its diagnostic and treatment capabilities and its
broad spectrum of programs and services, as well as breakthroughs in biomedical
research and superlative medical education. It ranks among the top 10
non-university hospitals in the nation for its research activities and is fully
accredited by the Association for the Accreditation of Human Research Protection
Programs, Inc. (AAHRPP). Additional information is available at http://www.cedars-sinai.edu.
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