Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety.
OBJECTIVE
The study assessed the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers in the treatment of acute mania.


METHODS
This 3-week randomized, double-blind, placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a mood stabilizer (lithium or divalproex) and placebo, risperidone, or haloperidol. The primary efficacy measure was the Young Mania Rating Scale. Other assessments used the Brief Psychiatric Rating Scale, the Clinical Global Impression scale, and safety measures.


RESULTS
The trial was discontinued by 25 (49%) of the 51 placebo group patients, 18 (35%) of the 52 risperidone group patients, and 28 (53%) of the 53 haloperidol group patients. Mean modal doses were 3.8 mg/day (SD=1.8) of risperidone and 6.2 mg/day (SD=2.9) of haloperidol. Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group, compared with the placebo group. Young Mania Rating Scale total scores improved with risperidone and with haloperidol both in patients with psychotic features and in those without psychotic features at baseline. Extrapyramidal Symptom Rating Scale total scores at endpoint were significantly higher in the haloperidol patients than in the placebo patients. Antiparkinsonian medications were received by 8%, 17%, and 38% of patients in the placebo, risperidone, and haloperidol groups, respectively.


CONCLUSIONS
Risperidone plus a mood stabilizer was more efficacious than a mood stabilizer alone, and as efficacious as haloperidol plus a mood stabilizer, for the rapid control of manic symptoms and was well tolerated.
Sachs
Gary S
GS
Bipolar Research Program, Department of Psychiatry, Massachusetts General Hospital, 50 Staniford Street, Suite 580, Boston, MA 02114, USA. sachsg@aol.com
Grossman
Fred
F
Ghaemi
S Nassir
SN
Okamoto
Akiko
A
Bowden
Charles L
CL
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D018692:Antimanic Agents / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000188:drug therapy; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D018967:Risperidone / Q000627:therapeutic use*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
D018692:Antimanic Agents; D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D010919:Placebos; D014635:Valproic Acid; D008094:Lithium; D006220:Haloperidol; D018967:Risperidone