WHERE: The Journal of Clinical Psychiatry
"Risperidone in the Treatment of Mania"

WHEN: June 1996 J Clin Psychiatry 1996; 57:249-253

WHO: Mauricio Tohen, M.D., Dr. P.H.; Carlos A. Zarate, Jr., M.D.;
Franca Centorrino, M.D.; James I. Hegarty, M.D., M.P.H.;
Michael Froeschl, and Silvina B. Zarate, Harvard Medical
School, Boston, and McLean Hospital, Belmont, Massachusetts

WHAT: In an open-label pilot study, risperidone appeared to be an
efficacious and well-tolerated antimanic agent when used in
combination with mood-stabilizing drugs. Controlled
studies are warranted to evaluate the use of risperidone as
an adjunctive treatment in patients who have acute mania
with psychotic features./

BELMONT, Mass., June 27 /PRNewswire/ -- Risperidone (RISPERDAL(R)) may
provide effective treatment of patients experiencing an acute episode of
bipolar disorder, manic type, with psychotic features, according to the
results of a pilot study reported this month in The Journal of Clinical
Researchers at McLean Hospital and Harvard Medical School, led by
Mauricio Tohen, M.D., Dr. P.H., set out to investigate whether risperidone,
a novel antipsychotic agent with efficacy shown superior to haloperidol in
the treatment of positive and negative symptoms of schizophrenia, would
also be effective in the treatment of affective disorders with a psychotic
component. They conducted an open-label pilot study in 15 patients at
McLean Hospital who had acute mania with psychotic features. Inclusion
criteria included minimum scores of 45 on the 24-item modified Brief
Psychiatric Rating Scale (BPRS) and 20 on the Young Mania Rating Scale
(YMRS). Patients were allowed to continue taking previously prescribed
mood-stabilizing drugs, and risperidone was administered orally in the
morning and evening for 6 weeks.
Of the 13 patients who completed two weeks of treatment, eight had a 50
percent improvement in BPRS scores, and all 13 had at least a 25 percent
improvement. Of the eight patients who completed six weeks of treatment,
seven had a 50 percent improvement, and all eight had at least a 25 percent
improvement. Similar results were obtained with the YMRS. By Week two, 10
of the 13 patients remaining in treatment had a 50 percent improvement in
YMRS scores, and 12 of these 13 had at least a 25 percent improvement. By
Week six, all eight patients remaining in treatment had a 75 percent
Bipolar disorder is a major public health problem, affecting up to 2.5
percent of the population. Before treatments became available, bipolar
patients spent one fourth of their adult life hospitalized and one fourth
in a disabled condition, at a cost of more than $5 million per patient. At
present, the treatments available for patients with bipolar disorder are
limited in number. Lithium and valproate are the most widely used
mood-stabilizers. How to treat those patients who do not tolerate or do
not respond to the current antimanic agents is a pressing treatment
All of the patients in Tohen and colleagues' study had been receiving
mood-stabilizers before hospitalization and study initiation, suggesting
that these patients as a whole were nonresponsive or poorly responsive to
traditional therapy. Prestudy rating scale scores also indicated that
their bipolar population was severely symptomatic. Their preliminary
positive findings add to the growing scientific literature supporting the
use of atypical antipsychotics for the treatment of affective disorders.
In addition to the improvement noted in all patients, the researchers
emphasized that the medication was well- tolerated and that the results
"clearly show that no patient worsened." If the encouraging results of
Tohen and colleagues are replicated in controlled studies, risperidone may
become a treatment option for this patient population.
Given the methodological limitations of their study, including open
design, small sample size, and limited period of observation, the
researchers urge that the results be interpreted with caution. They
highlighted several variables that may relate to study outcome. In
particular, they noted that all patients in the current study received
concurrent treatment with mood-stabilizing drugs. Additionally, all of
their patients were treated with relatively low doses of risperidone
(ranging from 2 mg/day to a maximum dose of 6 mg/day).
Risperidone, introduced in the United States in 1994, belongs to a new
chemical class -- the benzisoxazol derivatives. It has a unique
pharmacological profile displayed by its potent serotonin (5-HT2) and
dopamine (D2) receptor antagonism. This profile may explain its
antipsychotic and mood-stabilizing effects, along with its low incidence of
extrapyramidal symptoms. Because up to 60% of patients with acute mania
are now treated with antipsychotic drugs, the lower potential of
risperidone to cause adverse effects when compared with conventional
antipsychotic agents is an important consideration for patient compliance
with the medication regimen. Traditionally, clinicians have attempted to
limit antipsychotic drug exposure in mood disordered patients because this
population has been reported to be at increased risk for extrapyramidal
Dr. Tohen is an associate professor of psychiatry at Harvard Medical
School, chief of the Psychiatric Epidemiology Laboratory at the Harvard
School of Public Health in Boston, and clinical director of the Bipolar and
Psychotic Disorders Program at McLean Hospital in Belmont, Massachusetts.
McLean Hospital is a nonprofit center for psychiatric and chemical
dependency treatment, teaching, and research, located 10 miles west of
Boston. Consistently ranked as one of the nation's best hospitals for
mental health care, McLean maintains the largest research program of any
private psychiatric hospital. McLean is a teaching facility of Harvard
Medical School, an affiliate of Massachusetts General Hospital and a member
of the Partners HealthCare System.
The Journal of Clinical Psychiatry is a monthly peer-reviewed journal
that publishes articles of relevance to practicing clinical psychiatrists.
This publication is one of the most widely read psychiatric journals and is
indexed by all major data bases, including Index Medicus.
-0- 6/27/96
/CONTACT: Susan Craig, Public Affairs of McLean Hospital, 617-855-2110/

CO: McLean Hospital; Journal of Clinical Psychiatry ST: Massachusetts IN: