Tohen M, Goldberg JF, Gonzalez-Pinto
Arrillaga AM, Azorin JM, Vieta E, Hardy-Bayle MC, Lawson WB, Emsley RA, Zhang
F, Baker RW, Risser RC, Namjoshi MA, Evans AR, Breier A.
Lilly Research Laboratories, Indianapolis, Ind 46225, USA. email@example.com
12-week, double-blind comparison of olanzapine vs haloperidol in the treatment
of acute mania.
Arch Gen Psychiatry. 2003 Dec;60(12):1218-26.
This randomized controlled trial compares the efficacy and safety of olanzapine
vs haloperidol, as well as the quality of life of patients taking these drugs,
in patients with bipolar mania. METHODS: The design consisted of 2 successive,
6-week, double-blind periods and compared flexible dosing of olanzapine (5-20
mg/d, n = 234) with haloperidol (3-15 mg/d, n = 219). RESULTS: Rates of remission
(Young-Mania Rating Scale score of < or =12 and 21-item Hamilton Rating Scale
for Depression score of < or =8 at week 6) were similar for olanzapine- and
haloperidol-treated patients (52.1% vs 46.1%, respectively; P =.15). For the subgroup
of patients whose index episode did not include psychotic features, rates of remission
were significantly greater for the olanzapine group compared with the haloperidol
group (56.7% vs 41.6%, P =.04). Relapse into an affective episode (mania and/or
depression) occurred in 13.1% and 14.8% of olanzapine- and haloperidol-treated
patients, respectively (P =.56). Switch to depression occurred significantly more
rapidly with haloperidol than with olanzapine when using survival analysis techniques
(P =.04), and significantly more haloperidol-treated patients experienced worsening
of extrapyramidal symptoms, as indicated by several measures. Weight gain was
significantly greater in the olanzapine group compared with the haloperidol group
(2.82 vs 0.02 kg, P<.001). The olanzapine group had significant improvement
in quality of life on several dimensions compared with the haloperidol group.
CONCLUSIONS: These data suggest that olanzapine does not differ from haloperidol
in achieving overall remission of bipolar mania. However, haloperidol carries
a higher rate of extrapyramidal symptoms, whereas olanzapine is associated with
weight gain." [Abstract]
L, Namjoshi MA, Zhang F, Gandhi G, Edgell ET, Tohen M, Breier A, Haro JM.
Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. firstname.lastname@example.org
versus haloperidol in the treatment of acute mania: clinical outcomes, health-related
quality of life and work status.
Int Clin Psychopharmacol.
"We aimed to compare clinical outcomes, health-related
quality of life (HRQOL) and work status associated with olanzapine and haloperidol
treatment in patients with bipolar disorder. This double-blind, randomized controlled
trial, comparing flexible dosing of olanzapine (5-20 mg/day, n = 234) to haloperidol
(3-15 mg/day, n = 219), consisted of a 6-week acute phase, followed by a 6-week
continuation phase. Symptomatic remission rates were similar for olanzapine- and
haloperidol-treated patients at weeks 6 and 12. At week 6, significant changes
in five dimensions of the Medical Outcomes Study 36-Item Short Form Health Survey
(SF-36) [general health (P = 0.010), physical functioning (P < 0.001), role
limitations due to physical problems (P < 0.001), social functioning (P <
0.05) and vitality (P < 0.01)] and the SF-36 physical components summary score
were found in favour of olanzapine compared to haloperidol. At week 12, olanzapine
treatment maintained the significantly favourable HRQOL changes. At the end of
week 12, patients on olanzapine showed significantly greater improvement than
haloperidol in work activities impairment and household activities impairment
scores on the Streamlined Longitudinal Interview Clinical Evaluation from the
Longitudinal Interval Follow-up Evaluation (SLICE/LIFE) activities impairment
scores. Subgroup analyses revealed that olanzapine treatment significantly increased
a proportion of employed patients and their weekly paid working hours. In conclusion,
compared to haloperidol, olanzapine treatment was comparably effective in the
remission of bipolar mania and significantly improved HRQOL and work status in
patients with bipolar I disorder." [Abstract]
Bahk WM, Shin YC, Woo JM, Yoon BH, Lee JS, Jon DI, Chung SK, Choi SK, Paik IH, Pae CU
Topiramate and divalproex in combination with risperidone for acute mania: a randomized open-label study.
Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jan;29(1):115-21.
Mood stabilizers and atypical antipsychotics are commonly combined for the treatment of bipolar mania. The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting. Seventy-four patients who met the DSM-IV criteria for bipolar mania were enrolled in this study. In order to assess the efficacy and the extrapyramidal symptoms (EPS), the Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale (SARS) were measured at the baseline and at weeks 1, 3 and 6. From the baseline to the endpoint, the YMRS and CGI scores were reduced by 67.9% and 56.6% in the topiramate plus risperidone group (TPMG). The YMRS and CGI scores were also reduced by 63.7% and 58.2% in the divalproex plus risperidone group (DVPG). The weight and body mass index (BMI) increased significantly by 3.6% and 3.3% from the baseline to the endpoint in the DVPG, while they decreased by 0.5% and 0.4%, respectively, with no significant difference in the TPMG. There were no serious adverse events in either group. Despite the methodological limitations, topiramate was effective and tolerable for treating acute mania and may also be a promising alternative to a weight-gain liable mood stabilizer (MS) such as divalproex. [Abstract]
Segal J, Berk M, Brook S.
Department of Psychiatry,
University of the Witwatersrand Medical School, Johannesburg, South Africa.
compared with both lithium and haloperidol in mania: a double-blind randomized
Clin Neuropharmacol. 1998 May-Jun;21(3):176-80.
reports and studies of other neuroleptics suggest the efficacy of risperidone
in the treatment of mania. Forty-five inpatients with DSM-IV mania were studied
in a 28-day randomized, controlled, double-blind trial of either 6 mg daily of
risperidone, 10 mg daily of haloperidol, or 800 to 1200 mg daily of lithium. The
patients in all three groups showed a similar improvement on the total score for
all rating scales at day 28 (Brief Psychiatric rating scale; lithium 9.1, haloperidol
4.9, risperidone 6.5, F = 1.01, df = 2, p = 0.37; Mania rating scale; lithium
15.7, haloperidol 10.2, risperidone 12.4, F = 1.07, df = 2, p = 0.35 [analysis
of variance]). The Global Assessment of Functioning and Clinical Global Impression
data showed a similar pattern of improvement. This study suggests that risperidone
is of equivalent efficacy to lithium and haloperidol in the management of acute
mania. The extrapyramidal side effects of risperidone and haloperidol were not
significantly different." [Abstract]
SL, Keck PE, Stanton SP, Tugrul KC, Bennett JA, Strakowski SM.
Psychiatry, University of Cincinnati College of Medicine, Ohio, 45267, USA.
randomized comparison of divalproex oral loading versus haloperidol in the initial
treatment of acute psychotic mania.
J Clin Psychiatry. 1996
"BACKGROUND: Uncontrolled evidence suggests that divalproex
administered via the oral loading strategy of 20 mg/kg/day may produce clinically
significant antimanic response within 3 days of treatment in some patients. We
conducted a prospective study to compare the antimanic response of divalproex
oral loading with that of haloperidol in the initial treatment of acute psychotic
mania. METHOD: After a < or = 1-day screening period, 36 consecutive hospitalized
patients with bipolar disorder, manic or mixed phase and with psychotic features,
were randomly assigned to receive either divalproex 20 mg/kg/day or haloperidol
0.2 mg/kg/day for 6 full days, without other psychotropic agents except lorazepam
up to 4 mg/day for management of agitation. Serum valproate concentrations were
measured after 1 day of treatment. Response was measured daily by a blind rater
using the Young Mania Rating Scale and the Scale for Assessment of Positive Symptoms.
RESULTS: Divalproex oral loading and haloperidol were equally effective in acutely
reducing manic and psychotic symptoms. The greatest rate of improvement for both
drug regimens occurred over the first 3 full days of treatment. Side effects were
infrequent and minor for both treatments, except for extrapyramidal side effects
which were significantly more common with haloperidol. CONCLUSION: Divalproex
oral loading may produce rapid onset of antimanic and antipsychotic response comparable
to that of haloperidol and with minimal side effects in the initial treatment
of acute psychotic mania in a subset of bipolar patients." [Abstract]
Small JG, Klapper MH, Marhenke JD, Milstein V, Woodham
GC, Kellams JJ.
Indiana University School of Medicine, Department of Psychiatry,
Larue D. Carter Memorial Hospital, Indianapolis, IN 46202, USA.
combined with carbamazepine or haloperidol in the treatment of mania.
"Hospitalized manic patients were withdrawn from
psychoactive medications for 2 weeks after which they were randomized to double-blind
treatment with carbamazepine plus lithium [CBZ-Li] or haloperidol plus lithium
[HAL-Li] with benztropine. Unit dosages of Li 300 mg, CBZ 200 mg and HAL 2 mg
were titrated to therapeutic plasma levels and maintained for 8 weeks. No rescue
medications were permitted after 3 weeks. Standard ratings of psychopathology
and side effects were accomplished weekly. Sixty patients entered the study but
only 33 remained for randomization after drug washout. By 8 weeks both groups
were improved from baseline without statistically reliable differences between
them. However HAL-Li patients had more extrapyramidal side effects that were major
reasons for dropout, whereas CBZ-Li patients were more often noncompliant and
initially required more rescue medications. We conclude that either combination
treatment can be beneficial but CBZ-Li has the advantage because of fewer neurologic
side effects." [Abstract]
T, Webb A, Paul B, Carmody T, Kraemer H, Rush AJ.
Department of Psychiatry,
University of Texas Southwestern Medical Center, Dallas 75235-9070, USA.
outcome in a randomized 1-year trial of clozapine versus treatment as usual for
patients with treatment-resistant illness and a history of mania.
J Psychiatry. 1999 Aug;156(8):1164-9.
"OBJECTIVE: Case series and follow-up
studies suggest that clozapine may have mood-stabilizing properties in addition
to antipsychotic action in patients with schizoaffective disorder, bipolar type,
and bipolar I disorder, but the generalizability of these findings is limited.
This article describes a randomized, open study of clozapine add-on therapy versus
treatment as usual for patients with treatment-resistant illness and a history
of mania. METHOD: Thirty-eight patients meeting the DSM-IV criteria for schizoaffective
or bipolar disorder that was deemed treatment-resistant were randomly assigned
to clozapine add-on treatment (N = 19) or treatment as usual (no clozapine) (N
= 19) and followed up for 1 year. Patients received monthly ratings on the Brief
Psychiatric Rating Scale, Clinical Global Impression scale, Bech-Rafaelsen Mania
Scale, Hamilton Depression Rating Scale, Scale for the Assessment of Positive
Symptoms, Scale for the Assessment of Negative Symptoms, Abnormal Involuntary
Movement Scale, and a 40-item side effect checklist. Differences between treatment
groups were assessed according to a pattern-mix random-regression model. An additional
analysis compared group differences in rating scale scores against relative time
in the study. RESULTS: Significant between-group differences were found in scores
on all rating scales except the Hamilton depression scale. Total medication use
over 1 year significantly decreased in the clozapine group. No significant differences
between groups in somatic complaints were noted. The subjects with nonpsychotic
bipolar I disorder who received clozapine showed a degree of improvement similar
to that of the entire clozapine-treated group. Clozapine dose was significantly
higher for the patients with schizoaffective illness than for those with bipolar
disorder. CONCLUSIONS: The results of this study support clozapine's independent
mood-stabilizing property. They demonstrate that clozapine use was associated
with significant clinical improvement relative to treatment as usual." [Abstract]
B, Scherillo P, Benedetti F, Crespi G, Colombo C, Smeraldi E.
Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, University
of Milan, School of Medicine, Italy.
Response to clozapine in acute
mania is more rapid than that of chlorpromazine.
Psychopharmacol. 1997 Mar;12(2):109-12.
"The purpose of the present study
was to compare the efficacy of clozapine with that of chlorpromazine in an open
label manner (both given in association with lithium salts) in the treatment of
acute mania. Thirty hospitalized manic patients were entered into the study. All
patients met DSM-IV criteria for bipolar disorder, Manic Episode; 27 patients
completed the study and three patients dropped for noncompliance. The duration
of the study was 3 weeks. Patients were randomly assigned to two treatment groups;
group 1 (n = 15) was treated with clozapine at a mean dose of 166 mg/day and group
2 (n = 12) was treated with chlorpromazine at a mean dose of 310 mg/day. Manic
symptomatology was rated on Young Rating Scale for Mania (YRSM) each week; side
effects were recorded on dosage records and treatment emergent symptoms; extrapyramidal
acute side effects were rated on the Simpson-Angus Rating Scale performed at the
beginning of the study and after 3 weeks of treatment. A two-way repeated measures
analysis of variance on YRMS scores showed a significant time effect (p < 0.0001)
and a significant time-group interaction (p < 0.0001). Post-hoc comparison
between the two groups showed a significant difference after 2 weeks of treatment
(p = 0.0001), with clozapine treated patients showing lower YRSM scores than chlorpromazine
treated patients. YRSM scores at the end of the study were not significantly different.
Patients treated with clozapine showed a more rapid trend toward amelioration.
No clinically relevant side effect was observed during the study." [Abstract]
Sikdar S, Kulhara P, Avasthi A, Singh H.
Institute of Medical Education and Research, Chandigarh, India.
chlorpromazine and electroconvulsive therapy in mania.
J Psychiatry. 1994 Jun;164(6):806-10.
"We report the efficacy of combined
chlorpromazine and electroconvulsive therapy (ECT) in the treatment of mania.
Two groups of 15 manic patients received eight ECT sessions either actual or simulated,
in a double-blind, controlled study. All patients also received 600 mg of chlorpromazine
daily until the sixth session. Results indicate that the group receiving the combination
of chlorpromazine and ECT did significantly better than the other group."
Keck PE Jr, Marcus R, Tourkodimitris S, Ali M,
Liebeskind A, Saha A, Ingenito G; Aripiprazole Study Group.
Program, Department of Psychiatry, University of Cincinnati College of Medicine,
PO Box 670559, Cincinnati, OH 45267-0559, USA. email@example.com
placebo-controlled, double-blind study of the efficacy and safety of aripiprazole
in patients with acute bipolar mania.
Am J Psychiatry. 2003
"OBJECTIVE: The authors compared the efficacy and safety
of aripiprazole, a novel antipsychotic, to placebo for treatment of patients in
an acute manic or mixed episode of bipolar disorder. METHOD: This 3-week, multicenter,
double-blind study randomly assigned 262 bipolar disorder patients in an acute
manic or mixed episode to aripiprazole, 30 mg/day (reduced to 15 mg/day if needed
for tolerability), or placebo. Patients remained hospitalized for at least 2 of
the weeks. The primary efficacy measure was mean change from baseline in total
score on the Young Mania Rating Scale; response was defined as a decrease in score
of > or =50%. RESULTS: Aripiprazole produced statistically significant mean
improvements in total score on the Young Mania Rating Scale compared with placebo
(-8.2 versus -3.4, respectively) and produced a significantly higher response
rate (40% versus 19%). For key efficacy variables (response per Young Mania Rating
Scale; Clinical Global Impression-Bipolar Version scores for severity of illness
[mania] and change from preceding phase [mania]), aripiprazole separated from
placebo by day 4. The completion rate was significantly higher with aripiprazole
than with placebo (42% versus 21%). Discontinuations due to adverse events did
not differ significantly between the aripiprazole and placebo groups. There were
no significant changes in body weight versus placebo, and aripiprazole was not
associated with elevated serum prolactin or QTc prolongation. CONCLUSIONS: Aripiprazole
had significantly greater efficacy than placebo for the treatment of bipolar disorder
patients in acute manic or mixed episodes and was safe and well tolerated in this
randomized controlled trial." [Abstract]
PE Jr, Versiani M, Potkin S, West SA, Giller E, Ice K; Ziprasidone in Mania Study
Department of Psychiatry, University of Cincinnati College of Medicine,
OH 45627-0559, USA. firstname.lastname@example.org
Ziprasidone in the treatment
of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized
Am J Psychiatry. 2003 Apr;160(4):741-8.
The study evaluated the efficacy and tolerability of ziprasidone, compared with
placebo, in the treatment of adult patients with acute bipolar mania. METHOD:
Patients with a primary DSM-IV diagnosis of bipolar I disorder and a current manic
or mixed episode (confirmed by the Structured Clinical Interview for DSM-IV Axis
I Disorders, Patient Edition) (N=210) were randomly assigned in a 2:1 ratio to
3 weeks of double-blind treatment with ziprasidone (40-80 mg twice daily) or placebo.
Efficacy was assessed with the Schedule for Affective Disorders and Schizophrenia,
Change Version (which contains the Mania Rating Scale), Positive and Negative
Syndrome Scale, Clinical Global Impression (CGI) severity scale, CGI improvement
scale, and Global Assessment of Functioning Scale. Primary efficacy variables
were differences from baseline to endpoint (last observation carried forward)
in mean Mania Rating Scale and CGI severity scale scores between the ziprasidone
and placebo groups. Safety evaluations included monitoring of adverse events,
vital signs, electrocardiogram results, and clinical laboratory values and assessment
of movement disorders and akathisia. RESULTS: Ziprasidone produced rapid, sustained
improvements relative to baseline and placebo on all primary and most secondary
efficacy measures at endpoint. Significant improvements were typically observed
within 2 days after treatment commenced and were maintained throughout the 3 weeks.
Ziprasidone was well tolerated and associated with a low rate of extrapyramidal
symptoms; neither weight gain nor clinically significant changes in vital signs
or other safety parameters were observed with ziprasidone. CONCLUSIONS: Ziprasidone
monotherapy was significantly superior to placebo in reducing symptoms of acute
mania in patients with bipolar I disorder. Onset of action was rapid, and tolerability
of ziprasidone was generally comparable to that of placebo." [Abstract]
Smulevich AB, Khanna S, Eerdekens M, Karcher K, Kramer M, Grossman F
Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol.
Eur Neuropsychopharmacol. 2005 Jan;15(1):75-84.
In a randomized, double-blind trial, patients with acute bipolar mania received 1-6 mg/day of risperidone, 2-12 mg/day of haloperidol, or placebo for 3 weeks, followed by double-blind risperidone or haloperidol for 9 weeks. Of 438 patients, 154 were randomized to risperidone, 144 to haloperidol, and 140 to placebo. The mean+/-S.D. modal doses were 4.2+/-1.7 mg/day of risperidone and 8.0+/-3.6 mg/day of haloperidol during the initial 3-week phase and 4.1+/-1.8 and 7.4+/-3.7 mg/day during the 12-week period. At week 3, mean Young Mania Rating Scale (YMRS) score reductions from baseline were significantly greater in patients receiving risperidone than placebo (p<0.001). Differences between risperidone and haloperidol on this efficacy measure were not significant. Further reductions in YMRS scores were seen in patients receiving risperidone or haloperidol during the subsequent 9 weeks. No unexpected adverse events were reported. Extrapyramidal disorder and hyperkinesias, the most commonly reported adverse events with antipsychotic use, occurred less frequently with risperidone than haloperidol. We conclude that risperidone monotherapy was an effective and well-tolerated treatment for bipolar mania and that efficacy was maintained over the long term. [Abstract]
Shelton RC, Stahl SM
Risperidone and paroxetine given singly and in combination for bipolar depression.
J Clin Psychiatry. 2004 Dec;65(12):1715-9.
BACKGROUND: Bipolar depression is a major clinical problem that remains under-researched. The current study was intended to evaluate the effects of the novel antipsychotic risperidone, the selective serotonin reup-take inhibitor (SSRI) paroxetine, and the combination in patients with bipolar disorder. METHOD: Thirty patients with DSM-IV bipolar (I or II) disorder, depressed phase, who were receiving a stable dose of a mood stabilizer were randomly assigned to 12 weeks of double-blind treatment with risperidone (plus placebo), paroxetine (plus placebo), or the combination of risperidone and paroxetine. Data were gathered from August 1999 to September 2001. RESULTS: All 3 groups experienced significant reductions in depression ratings from baseline to endpoint; there were no significant differences in outcome between groups. There were statistically significant differences in paroxetine dose contrasting paroxetine plus placebo against the combined condition. The switch rate into mania or hypomania was very low, with only 1 patient in the paroxetine plus placebo condition experiencing mild hypomania. CONCLUSION: These results suggest that risperidone, paroxetine, and the combination of risperidone and paroxetine are equally but modestly effective when added to a mood stabilizer in bipolar depression. The paroxetine dose differed between groups, possibly because of drug-drug interactions. Using another SSRI in the combined condition could have produced a more robust effect and should be tested. [Abstract]
RM, Keck PE Jr, Kramer M, Karcher K, Canuso C, Eerdekens M, Grossman F.
of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston,
TX 77555, USA.
Rapid antimanic effect of risperidone monotherapy:
a 3-week multicenter, double-blind, placebo-controlled trial.
J Psychiatry. 2004 Jun;161(6):1057-65.
OBJECTIVE: This study evaluated the
efficacy and safety of risperidone monotherapy in the treatment of acute bipolar
mania. METHOD: Patients with DSM-IV bipolar I disorder experiencing an acute manic
episode (baseline Young Mania Rating Scale score >/==" BORDER="0">20)
were randomly assigned to 3 weeks of treatment with risperidone (flexible dose:
1-6 mg/day) or placebo. The primary efficacy measure was the mean baseline-to-endpoint
change in total score on the Young Mania Rating Scale. Secondary efficacy measures
included the Clinical Global Impression (CGI) severity rating and scores on the
Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale,
and Global Assessment Scale (GAS). Safety assessments consisted of monitoring
adverse events, vital signs, electrocardiogram and laboratory results, and scores
on the Extrapyramidal Symptom Rating Scale. RESULTS: Subjects (N=259) received
treatment with either risperidone (N=134) or placebo (N=125). The mean modal dose
of risperidone was 4.1 mg/day. Improvement in mean Young Mania Rating Scale total
score (adjusted for covariates) was significantly greater in the risperidone than
in the placebo group at endpoint (mean change=-10.6 [SD=9.5] versus -4.8 [SD=9.5],
respectively), with significant between-group differences seen as early as 3 days
after start of treatment (change with risperidone: mean=-6.8 [SD=5.8]; change
with placebo: mean=-4.0 [SD=5.8]) and continuing throughout all time points. Improvements
in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating
Scale, Positive and Negative Syndrome Scale, and GAS were also significantly greater
among patients receiving risperidone than those given placebo. The most common
adverse event reported among risperidone patients was somnolence. While Extrapyramidal
Symptom Rating Scale scores were significantly greater in patients receiving risperidone,
mean total and subscale scores were low. CONCLUSIONS: Risperidone monotherapy
was significantly more efficacious than placebo in the treatment of acute mania
and demonstrated a rapid onset of action. Risperidone was well tolerated by patients
in this study. [Abstract]
CL, Myers JE, Grossman F, Xie Y.
University of Texas Health Science Center,
San Antonio, TX 78229, USA.
Risperidone in combination with mood
stabilizers: a 10-week continuation phase study in bipolar I disorder.
Clin Psychiatry. 2004 May;65(5):707-14.
BACKGROUND: Combination therapy (risperidone
and a mood stabilizer) for patients with a history of bipolar disorder (DSM-IV)
and hospitalized for treatment of a manic episode was assessed in a 13-week study.
METHOD: Subjects received flexible doses of a mood stabilizer (lithium or divalproex)
plus placebo, risperidone, or haloperidol in a 3-week double-blind study. They
could then enter a 10-week open-label study during which they received risperidone
combined with a mood stabilizer. RESULTS: Of the 156 patients enrolled in the
3-week study, 85 entered the 10-week open-label extension, of whom 48 completed
10 weeks of treatment. The mean +/- SE doses of risperidone were 3.8 +/- 0.3 mg/day
during the 3-week study and 3.1 +/- 0.2 mg/day during the 10-week study. At double-blind
endpoint, mean reductions in Young Mania Rating Scale (YMRS) scores were significantly
greater in patients receiving risperidone plus mood stabilizer than in those receiving
placebo plus mood stabilizer (-14.3 vs. -8.2, p <.001). Further significant
(p <.001) reductions were seen during the 10 weeks of treatment with risperidone
plus mood stabilizer. Symptom remission (YMRS score <or= 12) was seen in 38
patients (79%) at the end of the 10-week study. Scores on the Brief Psychiatric
Rating Scale, Hamilton Rating Scale for Depression, and Clinical Global Impressions
scale improved significantly (p <.05) during both the 3-week and 10-week studies.
Treatment was well tolerated, and modest weight gain was observed during the 13-week
study period. CONCLUSION: The combination of risperidone and a mood stabilizer
was efficacious and well tolerated in the continuation treatment of patients initially
hospitalized for the management of an acute manic episode. [Abstract]
LN, Grossman F, Augustyns I, Vieta E, Ravindran A.
University of British Columbia,
Vancouver, Canada. email@example.com
Mood stabilisers plus
risperidone or placebo in the treatment of acute mania. International, double-blind,
randomised controlled trial.
Br J Psychiatry. 2003 Feb;182:141-7.
Few double-blind trials have examined the efficacy of a combination of a mood
stabiliser and an atypical antipsychotic in acute mania. AIMS: To determine the
efficacy of risperidone in combination with a mood stabiliser in acute mania.
METHOD: Patients taking a mood stabiliser were randomised to 3 weeks' treatment
with risperidone (n=75) or placebo (n=76). RESULTS: Young Mania Rating Scale (YMRS)
scores improved rapidly with significantly greater reductions at week 1 in the
risperidone group compared with the placebo group. At end-point YMRS scores decreased
by 14.5 and 10.3 points in the risperidone and placebo groups, respectively. Significant
improvements v. placebo (P<0.05) were noted in the risperidone group on several
other clinically meaningful measures. Additionally, a post hoc analysis excluding
carbamazepine-treated patients (plasma concentrations of risperidone active moiety
were 40% lower in this group) revealed significantly greater reductions (P=0.047)
in YMRS scores in the risperidone group than in the placebo group. Incidence of
adverse events was similar in both groups. CONCLUSIONS: Risperidone is superior
to placebo when used in combination with lithium or divalproex in acute mania."
GS, Grossman F, Ghaemi SN, Okamoto A, Bowden CL.
Bipolar Research Program,
Department of Psychiatry, Massachusetts General Hospital, 50 Staniford Street,
Suite 580, Boston, MA 02114, USA. firstname.lastname@example.org
Combination of a
mood stabilizer with risperidone or haloperidol for treatment of acute mania:
a double-blind, placebo-controlled comparison of efficacy and safety.
J Psychiatry. 2002 Jul;159(7):1146-54.
"OBJECTIVE: The study assessed
the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers
in the treatment of acute mania. METHOD: 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."
Bowden CL, Grunze H, Mullen J, Brecher M, Paulsson B, Jones M, Vågerö M, Svensson K
A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder.
J Clin Psychiatry. 2005 Jan;66(1):111-21.
OBJECTIVE: To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder. METHOD: In an international, multicenter, double-blind, parallel-group, 12-week study, patients with a DSM-IV diagnosis of bipolar I disorder (manic episode) were randomly assigned to treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or lithium. The primary efficacy measure was change from baseline in Young Mania Rating Scale (YMRS) score at day 21. Data were gathered from April 2001 to May 2002. RESULTS: More patients in the quetiapine (72/107) and lithium (67/98) groups completed the study compared with the placebo group (35/97). Improvement (reduction) in YMRS score was significantly greater for quetiapine than placebo at day 7 (-8.03 vs. -4.89; p < .01), and the difference between groups continued to increase over time to day 21 (-14.6 vs. -6.7; p < .001) and to endpoint at day 84 (-20.3 vs. -9.0; p < .001). Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 (53.3% vs. 27.4%; p < .001) and at day 84 (72.0% vs. 41.1%; p < .001). Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures. Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure. The most common adverse events for quetiapine were dry mouth, somnolence, and weight gain, while lithium was associated with tremor and insomnia. The quetiapine and placebo groups had similar, low levels of extrapyramidal symptom-related adverse events. CONCLUSIONS: Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated. [Abstract]
G, Chengappa KN, Suppes T, Mullen JA, Brecher M, Devine NA, Sweitzer DE.
Bipolar Research Program, Massachusetts General Hospital, Boston, 02114, USA.
with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind,
Bipolar Disord. 2004 Jun;6(3):213-23.
Evaluate the efficacy and tolerability of quetiapine (QTP) combined with lithium
(Li) or divalproex (DVP) in the treatment of acute mania. METHODS: Patients were
randomized to 21 days of double-blind treatment with QTP plus Li/DVP, or placebo
(PBO) plus Li/DVP. QTP was rapidly dosed up to a maximum of 800 mg/day; Li was
dosed to 0.7-1.0 mEq/L; or DVP to 50-100 microg/mL. RESULTS: Fifty-six of 91 (61.5%)
individuals in the QTP + Li/DVP group compared with 49 of 100 (49%) taking PBO
+ Li/DVP completed the study. A significantly greater mean reduction in total
Young Mania Rating Scale (YMRS) score was observed at end-point in patients receiving
QTP + Li/DVP compared with those in the PBO + Li/DVP group (-13.76 versus -9.93;
p = 0.021). The response rate (> or =50% YMRS improvement) was significantly
higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients (54.3%
versus 32.6%; p = 0.005), as was the proportion of patients achieving clinical
remission (YMRS < 12) (45.7% versus 25.8%; p = 0.007). Patients receiving QTP
+ Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar
(CGI-BP) Severity of Illness scores (-1.38 versus -0.78; p = 0.001). The mean
last-week dose of QTP was 584 mg/day in patients meeting response criteria. Common
adverse events (at least 10% and twice the rate of Li/DVP) in the QTP + Li/DVP
group included somnolence, dry mouth, asthenia, and postural hypotension. CONCLUSIONS:
Quetiapine combined with either Li or DVP has superior efficacy compared with
Li or DVP monotherapy for treating patients with bipolar mania. Combination therapy
was well-tolerated and most adverse events were mild, withdrawal because of adverse
events being only 5% compared with 6% on Li or DVP monotherapy. [Abstract]
MP, Schwiers ML, Rosenberg HL, Strakowski SM.
Bipolar and Psychotic Disorders
Research Program, Department of Psychiatry, University of Cincinnati College of
Medicine, Cincinnati, OH 45267-0559, USA. email@example.com
double-blind, randomized, placebo-controlled study of quetiapine as adjunctive
treatment for adolescent mania.
J Am Acad Child Adolesc
Psychiatry. 2002 Oct;41(10):1216-23.
"OBJECTIVES: This randomized, double-blind,
placebo-controlled study examined the efficacy and tolerability of quetiapine
in combination with divalproex (DVP) for acute mania in adolescents with bipolar
disorder. It was hypothesized that DVP in combination with quetiapine would be
more effective than DVP alone for treating mania associated with adolescent bipolar
disorder. Furthermore, it was hypothesized that quetiapine would be well tolerated.
METHOD: Thirty manic or mixed bipolar I adolescents (12-18 years) received an
initial DVP dose of 20 mg/kg and were randomly assigned to 6 weeks of combination
therapy with quetiapine, which was titrated to 450 mg/day (n = 15) or placebo
(n = 15). Primary efficacy measures were change from baseline to endpoint in Young
Mania Rating Scale (YMRS) score and YMRS response rate. Safety and tolerability
were assessed weekly. RESULTS: The DVP + quetiapine group demonstrated a statistically
significantly greater reduction in YMRS scores from baseline to endpoint than
the DVP + placebo group (F(1,27) = 5.04, p =.03). Moreover, YMRS response rate
was significantly greater in the DVP + quetiapine group than in the DVP + placebo
group (87% versus 53%; Fisher exact test, p =.05). No significant group differences
from baseline to endpoint in safety measures were noted. Sedation, rated as mild
or moderate, was significantly more common in the DVP + quetiapine group than
in the DVP + placebo group. CONCLUSIONS: The findings of this study indicate that
quetiapine in combination with DVP is more effective for the treatment of adolescent
bipolar mania than DVP alone. In addition, the results suggest that quetiapine
is well tolerated when used in combination with DVP for the treatment of mania."
JC, Czobor P, Charles O, Tuma I, Winsberg B, Allen MH, Trujillo M, Volavka J.
Kline Institute, Orangeburg, New York 10962, USA. firstname.lastname@example.org
mania: haloperidol dose and augmentation with lithium or lorazepam.
Clin Psychopharmacol. 1999 Dec;19(6):500-5.
"Antipsychotic dosing for
acute mania has not been well studied. Combined treatment with lithium and an
antipsychotic is the most common treatment, but additional antimanic efficacy
of a lithium-antipsychotic combination beyond that of an antipsychotic alone has
not been well demonstrated. Furthermore, the possibility that lithium could affect
antipsychotic dose requirement is believed to have never been studied. In this
study, 63 acutely psychotic bipolar manic inpatients were randomly assigned to
receive double-blind treatment with 1 of 2 haloperidol doses, 25 mg/day or 5 mg/day,
for 21 days. In addition to haloperidol, subjects were randomly assigned to receive
concomitant treatment with placebo, standard lithium, or lorazepam 4 mg/day. The
high haloperidol dose produced greater improvement and more side effects than
did the low dose. Lithium added to the low dose produced a markedly greater clinical
response than did the low dose alone. Lorazepam did not improve the outcome for
the patients receiving low-dose haloperidol. The clinical response produced by
high-dose haloperidol was not enhanced by adding either lithium or lorazepam.
All treatment effects emerged by the fourth day of treatment and persisted. Used
alone, a haloperidol dose of 5 mg/day is too low for most manic patients, but
concomitant lithium produces a dose-dependent enhancement of haloperidol response.
Lorazepam 4 mg/day was insufficient to produce an advantage when added to low-dose
CA Jr, Tohen M.
Consolidated Department of Psychiatry, McLean Hospital, Harvard
Medical School, Belmont, Mass, USA. email@example.com
comparison of the continued use of antipsychotic treatment versus its discontinuation
in remitted manic patients.
Am J Psychiatry. 2004 Jan;161(1):169-71.
The goal of this study was to determine the benefits of the continued use of a
typical antipsychotic agent following remission from an acute manic episode. METHOD:
Immediately following remission of a manic episode treated with the combination
of a typical antipsychotic (perphenazine) and a mood stabilizer (lithium, carbamazepine,
or valproate), 37 patients were randomly assigned to 6 months of double-blind
treatment in which in addition to the mood stabilizer they received either continued
perphenazine treatment or placebo. RESULTS: Patients randomly assigned to continue
perphenazine treatment, relative to those who discontinued it, were more likely
to have a shorter time to depressive relapse, discontinue the study, and have
increased rates of dysphoria, depressive symptoms, and extrapyramidal symptoms.
CONCLUSIONS: There were no short-term benefits with the continued use of a typical
antipsychotic after achieving remission from an episode of acute mania. In fact,
its continued use was associated with detrimental effects." [Abstract]