New York State Psychiatric Institute, Columbia University Medical Center
2006
Zyprexa in schizophrenia proved to prevent brain loss
Jeffrey Lieberman, M.D.
published in NY
A new brain imaging study of recently diagnosed schizophrenia patients has found, for the first time, that the loss of gray matter typically experienced by patients can be prevented by one of the new atypical antipsychotic drugs, Zyprexa (olanzapine), but not by haloperidol, an older, conventional drug. The study also confirmed previous studies that show patients who experience less brain loss do better clinically. "This is a really big breakthrough," says the study's leader, Jeffrey Lieberman, M.D., director of the New York State Psychiatric Institute and chairman of psychiatry at Columbia University Medical Center. "The drugs we have for schizophrenia can't cure people who've been sick for years, but this study shows that the newer atypical drugs, if started early, can prevent the illness from progressing. If our findings are confirmed, one could argue that we should treat new patients with atypical drugs like Zyprexa (olanzapine) rather than older conventional medications such as haloperidol and chlorpromazine." Gray matter contains the bulk of the brains cell's and the billions of connections among the cells. Loss of gray matter in patients with schizophrenia has been linked to social withdrawal and progressive deterioration in cognition and emotion-which are among the least responsive symptoms to medications. To see if antipsychotic drugs could slow the initial brain changes in new patients, Dr. Lieberman and colleagues at 14 sites in North America and Europe measured brain volume and cognitive changes in 263 first-episode schizophrenia patients and 58 non-schizophrenic volunteers over a two-year period. Half of the patients received the atypical antipsychotic Zyprexa (olanzapine) and the other half took the conventional antipsychotic haloperidol. Dr. Lieberman initiated the study when he was professor of psychiatry at the University of North Carolina, which also coordinated the research. The study found that, on average, haloperidol-treated patients lost about two percent of their gray matter, or about 12 cubic centimeters. No changes were detected in the olanzapine-treated patients and the normal volunteers. Patients who lost gray matter, particularly in the frontal lobe of the brain, also had greater problems with cognitive functioning, as measured by tests of verbal fluency, verbal learning and memory. Schizophrenia has always been known as a disease that causes progressive worsening of symptoms and deterioration in function, but only in the last 10 years have researchers found that the brains of schizophrenics are also progressively deteriorating. "People used to think that the deterioration was inevitable, but now we're thinking that if you can prevent the acute episodes of psychosis in schizophrenia you can actually stop the loss of gray matter," Dr. Lieberman says. "It also gives us hope that we will be able to completely forestall the disease in the future by intervening before psychosis even begins," Dr. Lieberman adds. "In three to five years, we should have ways to identify which adolescents will become schizophrenic, and we can then begin to test the preventative power of treatments."
University of Pennsylvania School of Medicine 2006,Nov 22
Zyprexa is effective drug but may have metabolic effect
By Jeff Minerd, Reviewed by Zalman S. Agus
The newer atypical antipsychotic drugs may not always outperform the
old ones in managing schizophrenia, investigators said here. That's what
the results of the Clinical Antipsychotic Trials of Intervention Effectiveness
(CATIE) study suggested, said Rajiv Tandon, M.D., of the University of
Florida in Tallahassee. Dr. Tandon discussed the CATIE trial and its results
at a symposium held in conjunction with the U.S. Psychiatric & Mental
Health Congress here. The symposium was sponsored by Janssen pharmaceuticals
of Titusville, N.J. In CATIE, nearly 1,500 patients with schizophrenia
(ages 18 to 65) were recruited at 57 sites in the U.S. Participants were
randomly assigned to Zyprexa (olanzapine) at 7.5 to 30 mg per day, Triavil
(perphenazine) at 8 to 32 mg per day, Seroquel (quetiapine) at 200 to
800 mg per day, Risperdal (risperidone) at 1.5 to 6 mg per day, or Geodon
(ziprasidone) at 40 to 160 mg per day. Triavil is an older, typical antipsychotic
developed in the mid-1950s. This class of drugs is associated with extrapyramidal
side effects, Dr. Tandon noted. Follow-up in CATIE was 18 months. Endpoints
included time to discontinuation of a particular drug as well as efficacy
measures. Discontinuation of antipsychotic medications is common because
they don't work in all patients and because of adverse effects, including
metabolic side effects, extrapyramidal side effects, and weight gain,
Dr. Tandon said. Overall, 74% of patients discontinued their study medication
and switched to a new medication before 18 months, including: • 49%
of those assigned to Zyprexa. • 55% of those assigned to Risperdal.
• 65% of those assigned to Seroquel. • 70% of those assigned
to Geodon and Triavil. The time to discontinuation of treatment for any
cause was significantly longer in the Zyprexa group than in the Seroquel
(P<0.001) or Risperdal (P=0.002) group, but not in the Triavil (P=0.021)
or Geodon (P=0.028) group. The times to discontinuation because of intolerable
side effects were similar among the groups. However, Zyprexa was associated
with more discontinuation for weight gain or metabolic effects, and Triavil
was associated with more discontinuation for extrapyramidal effects. Zyprexa
was the most effective drug in terms of the rates of discontinuation,
but it was the "worst offender" in terms of metabolic side effects,
Dr. Tandon said. Furthermore, the efficacy of the typical antipsychotic
Triavil appeared similar to that of Seroquel, Risperdal, and Geodon in
patients at low risk for extrapyramidal side effects, he said. The CATIE
study suggests that in schizophrenic patients with a low risk for extrapyramidal
side effects, typical antipsychotics may work as well as the atypical
"if you can get the dosing just right," Dr. Tandon said. Individual
dosing is the key because there is considerable variation in how patients
respond to differing doses of antipsychotic drugs and in patients' susceptibility
to their side effects, Dr. Tandon said. Successfully managing schizophrenia
is crucial because the disease is such a heavy burden not only on individuals
but on the healthcare system, said Jacqueline M. Feldman, M.D., of the
University of Alabama at Birmingham, a second speaker at the symposium.
Half of all mental hospital beds are filled by patients with schizophrenia,
Dr. Feldman said. And about 16% of all patients getting healthcare services
have schizophrenia, she added. Half of schizophrenia patients attempt
suicide at some point during their lives, and 10% of them succeed. Finally,
one-third to two-thirds of the homeless in the United States have schizophrenia,
Dr. Feldman said.
Schizophr Res. 2005 May 12;
Patient characteristics and the likelihood of initiation on olanzapine
or risperidone among patients with schizophrenia.
Ren XS, Kazis LE, Lee AF, Huang YH, Hamed A, Cunningham F, Herz
L, Miller DR.
Health Services Department, Boston University School of Public Health,
Boston, MA, USA; Center for Health Quality, Outcomes, and Economic Research,
Veterans Affairs Medical Center, Bedford, MA, USA.
Although pharmacologic treatments are available for patients with schizophrenia,
little is known about how prescription patterns of atypical antipsychotic
agents are related to patient characteristics. In this study, we examined
the association between patient characteristics and the likelihood of
being initiated on olanzapine or risperidone, two of the most frequently
prescribed atypical agents for schizophrenia. We selected patients who
were diagnosed with schizophrenia or schizoaffective disorder based on
>/=1 inpatient or >/=2 outpatient ICD-9-CM codes (>/=7 days apart)
between 7/1/98 and 6/30/99 from the Veterans Health Administration (VA).
We classified patients into one of three types of initiation: (a) not
on olanzapine or risperidone, (b) not on any atypical agents, or (c) not
on any antipsychotic agents for 6 months, and then subsequently being
prescribed the target drugs. Using logistic regression, we examined whether
the odds ratio of being initiated on olanzapine versus risperidone are
related to patient sociodemographic and clinical characteristics. Compared
to risperidone initiators, olanzapine initiators used more drugs for psychiatric
conditions (including antiparkinsonian agents, typical antipsychotics,
and mood stabilizers) than risperidone initiators. On the other hand,
risperidone initiators had more medical comorbidities and more non-psychiatric
hospitalizations. Olanzapine and risperidone appear to be prescribed to
patients with different characteristics. Initiation of risperidone was
more common among patients who presented with more medical comorbid conditions,
whereas initiation of olanzapine was more common among patient who presented
with more mental comorbid conditions. Future research needs to determine
the reasons for those differences.
Rev Prat. 2005 Mar 15;55(5):513-22.
[Management of bipolar disorders]
[Article in French]
Gay C, Olie JP.
Clinique du Chateau, 11 bis, rue de la Porte Jaune, 92380 Garches.
gay@club-internet.fr
Management of the bipolar disorders is well codified and rests on the
prescription of mood stabilisers and psychotherapeutic measures. Mood
stabilisers have considerably improved the prognosis of bipolar disorder,
in limiting the number of recurrences. Lithium is still the leader of
mood stabilisers. It has a preventative and curative action that has effect
on the two poles of the illness. Carbamazepine, valpromide and its derivatives,
and olanzapine are indicated in the case of resistance or contra-indication
to lithium therapy and are more easily handled in the curative treatment
of the manic state. Other therapeutic measures have been proposed in order
to optimise the medical treatment and to act in anticipation of the precipitating
elements. Psycho educational measures, the roles of which have been undervalued
for a long time, are today the best-evaluated psychological treatments.
An elevated level of proof exists for these treatments. Their value is
stressed in most of the reference texts. The benefits of this complementary
approach exists on different levels: early recognition of symptoms that
announce a recurrence, improvement in compliance, acceptance of the illness,
better management of the social life, both professional and emotional,
control of precipitating factors... Recently published studies report
a reduction in the number of recurrences and relapses, a reduction in
the duration of hospitalisation, a better balance in the family life and
an improvement in compliance.
J Clin Psychiatry. 2005 May;66(5):611-616.
Analyses of Treatment-Emergent Mania With Olanzapine/Fluoxetine
Combination in the Treatment of Bipolar Depression.
Keck PE Jr, Corya SA, Altshuler LL, Ketter TA, McElroy SL, Case
M, Briggs SD, Tohen M.
From the Psychopharmacology Research Program, Department of Psychiatry, University of Cincinnati College of Medicine; Mental Health Service Line and General Clinical Research Center, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio (Drs. Keck and McElroy); Lilly Research Laboratories, Indianapolis, Ind. (Drs. Corya, Briggs, and Tohen and Mr. Case); Department of Psychiatry, UCLA School of Medicine, Los Angeles, Calif. (Dr. Altshuler); Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif. (Dr. Ketter); and the Department of Psychiatry, Harvard Medical School/McLean Hospital, Belmont, Mass. (Dr. Tohen).
BACKGROUND: Treatment-emergent mania is a potential risk when patients
with bipolar disorder are treated with antidepressant agents. These subanalyses
compare treatment-emergent mania rates in bipolar I depressed patients
treated with olanzapine, placebo, or olanzapine/fluoxetine combination.
METHOD: In this 8-week, double-blind investigation, patients with bipolar
I depression (DSM-IV criteria) (N = 833, baseline Montgomery-Asberg Depression
Rating Scale total score >/= 20) were randomly assigned to olanzapine
(5-20 mg/day, N = 370), placebo (N = 377), or olanzapine/fluoxetine combination
(6/25, 6/50, or 12/50 mg/day; N = 86). Treatment-emergent mania was evaluated
with the Young Mania Rating Scale (YMRS), the Clinical Global Impressions-Bipolar
Edition (CGI-BP) Severity of Mania scale, and adverse events records.
RESULTS: Overall rates of study discontinuation due to mania were low
and not significantly different among the therapy groups (p = .358). Incidence
of treatment-emergent mania (defined as a YMRS score < 15 at baseline
and >/= 15 at any subsequent visit) did not differ significantly among
therapy groups (olanzapine 5.7%, placebo 6.7%, olanzapine/fluoxetine combination
6.4%; p = .861). Subjects receiving olanzapine or olanzapine/fluoxetine
combination had greater mean decreases in YMRS scores than those receiving
placebo (p < .001 for both). Subjects receiving olanzapine or olanzapine/fluoxetine
combination also had greater mean decreases in CGI-BP scores than those
receiving placebo (p = .040 and p = .003, respectively). CONCLUSION: These
results suggest that olanzapine/fluoxetine combination does not present
a greater risk of treatment-emergent mania compared to olanzapine or placebo
over 8 weeks of acute treatment for bipolar I depression. Due to the cyclical
nature of bipolar disorder, patients taking olanzapine/fluoxetine combination
for bipolar depression should still be monitored for signs or symptoms
of emerging mania.
Arch Phys Med Rehabil. 2005 Mar;86(3):587-90.
Olanzapine for the treatment of hemiballismus: A case report.
Mukand JA, Fitzsimmons C, Wennemer HK, Carrillo A, Cai C, Bailey
KM.
Abstract Mukand JA, Fitzsimmons C, Wennemer HK, Carrillo A, Cai C, Bailey
KM. Olanzapine for the treatment of hemiballismus: a case report. Hemiballismus
is a rare movement disorder characterized by involuntary, large amplitude
movements of the limbs of 1 side of the body. We describe the case of
a man in his late sixties with slurred speech, agitation, and right-sided
hemiballismus resulting from a left thalamic hemorrhagic stroke. Treatment
with haloperidol was unsuccessful, but both the hemiballismus and agitation
diminished significantly after initiation of olanzapine (Zyprexa). The
improvement in the hemiballismus was quantified by recording the number
of hemiballistic movements that occurred while the patient performed standardized
30-minute sessions (daily for 5d). With the first task (reaching within
the base of support while seated), the average number of hemiballismic
movements per session decreased from a baseline of 23.5 to 3.0 in the
upper extremity and from 20.5 to 7.0 in the lower extremity. With the
second task (catching a ball while seated), the abnormal movements decreased
from 52 to 6.3 in the upper extremity and from 34.5 to 2.7 in the lower
extremity. This case suggests that olanzapine may be a valuable pharmacologic
alternative for patients with hemiballismus.
Am J Health Syst Pharm. 2005 Mar 15;62(6):610-5.
Health care costs for schizophrenia patients started on olanzapine
versus risperidone.
Russo PA, Smith MW, Namjoshi M.
Outcomes Research and Econometrics, The Medstat Group, Washington, DC.
PURPOSE: The change in direct medical costs for schizophrenia patients
who were started on olanzapine or risperidone and who were privately insured
was studied. METHODS: A retrospective analysis of 1996-1999 data from
the databases representing the health care experiences of individuals
employed by large organizations and their dependents was performed. The
sample included all individuals with a drug claim for olanzapine or risperidone,
a claim with a schizophrenia diagnosis within 90 days of the drug claim,
no claim for the same drug in the prior six months, and continuous health-plan
enrollment for 12 months before and after the prescription. RESULTS: The
sample included 162 patients initiated on olanzapine and 119 patients
initiated on risperidone. Demographic and clinical profiles were not significantly
different between groups. Annual schizophrenia-related prescription and
outpatient costs increased following initiation on olanzapine or risperidone
compared with the preinitiation period. This was partially offset by a
decrease in inpatient expenditures. Olanzapine initiators had higher outpatient
drug expenditures than risperidone initiators in the 12 months following
initiation (adjusted means, $2105 versus $1934) (p < 0.05), but there
was no significant difference between groups in total schizophrenia-related
payments ($5251 versus $4950). CONCLUSION: The total health care expenditure
related to treating schizophrenia was similar between privately insured
patients who were initiated on olanzapine and patients who were started
on risperidone.
Int J Neuropsychopharmacol. 2005 Mar 01;:1-12.
Clozapine, risperidone, olanzapine, and conventional antipsychotic
drug effects on glucose, lipids, and leptin in schizophrenic patients.
Smith RC, Lindenmayer JP, Bark N, Warner-Cohen J, Vaidhyanathaswamy
S, Khandat A.
Department of Psychiatry, New York University Medical School, NY, USA.
Some reports have indicated increased rates of diabetes and increased
prevalence of glucose and lipid abnormalities during treatment with second-generation
antipsychotics, with most concern raised about clozapine and olanzapine.
Most of the findings have come from case reports, retrospective examination
of laboratory values, and analysis of health-care claims databases. This
study investigated fasting levels of glucose, lipids, and leptin in a
non-randomized, cross- sectional study of 210 patients, with schizophrenic
or schizoaffective disorder, treated with a single antipsychotic medication
- clozapine, risperidone, olanzapine, or a conventional antipsychotic.
Glucose tolerance tests (GTT), with a 75-g glucose load, were preformed
in a subset of patients. In this sample most mean fasting glucose and
lipid levels were within the normal range and were not significantly different
across the four drug treatment groups. Patients treated with clozapine
and olanzapine had higher triglyceride levels than risperidone patients.
In patients receiving a GTT, risperidone-treated patients had higher glucose
levels at 1 h than patients treated with olanzapine, and there were more
patients on risperidone who met American Diabetes Association glucose
metabolic criteria for diagnosis of diabetes. Although there were no significant
differences in age or body mass index among the four drug groups, we cannot
rule out some potential biasing factors we did not assess which could
potentially influence our results. These include unknown physician preference
in drug selection based on their beliefs about the weight-inducing or
diabetes potential of different antipsychotics, differences in visceral
fat, and differences in patients' antipsychotic drug history.
Acta Psychiatr Scand. 2005 Mar;111(3):232-43.
Olanzapine vs. other antipsychotics in actual out-patient settings:
six months tolerability results from the European Schizophrenia Out-patient
Health Outcomes study.
Lambert M, Haro JM, Novick D, Edgell ET, Kennedy L, Ratcliffe
M, Naber D.
Centre for Psychosocial Medicine, Department for Psychiatry and Psychotherapy,
University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Lambert M, Haro JM, Novick D, Edgell ET, Kennedy L, Ratcliffe M, Naber
D. Olanzapine vs. other antipsychotics in actual out-patient settings:
six months tolerability results from the European Schizophrenia Out-patient
Health Outcomes study. Acta Psychiatr Scand 2004: 1-12. (c)Blackwell Munksgaard
2004.Objective: The European Schizophrenia Out-patient Health Outcomes
study is an observational study investigating treatment in schizophrenia.
We report treatment-emergent adverse events during the first 6 months
of treatment. Method: The rate of extrapyramidal symptoms (EPS), anticholinergic
use, weight gain and sexual related dysfunctions were assessed in 8400
out-patients. Results: Patients typical antipsychotics and risperidone
experienced significantly more EPS and anticholinergic use than patients
in the clozapine, olanzapine, and quetiapine cohorts. Patients treated
with amisulpride, typical antipsychotics and risperidone were significantly
more likely to have sexual related dysfunctions and/or amenorrhea. Increases
in weight and body mass index occurred in all cohorts, but were significantly
greater in the olanzapine and clozapine cohorts. Conclusion: Patients
treated with olanzapine, quetiapine and clozapine had better tolerability
outcomes regarding EPS and sexual related dysfunctions compared with patients
receiving risperidone, amisulpride and typicals. Patients treated with
olanzapine and clozapine had higher weight increases than patients treated
with risperidone, quetiapine and typicals.
Clin Neuropharmacol. 2005 Jan-Feb;28(1):50-3.
Case studies of adjunctive agents in clozapine-resistant schizophrenic
patients.
Kontaxakis VP, Ferentinos PP, Havaki-Kontaxaki BJ, Paplos KG,
Roukas DK, Christodoulou GN.
From the Department of Psychiatry, Eginition Hospital, University of Athens,
Athens, Greece.
Approximately 40%-70% of neuroleptic-resistant schizophrenic patients
are nonresponders even to clozapine. Several clozapine augmentation strategies
have come into clinical practice, although often without evidence-based
support. This study aims to critically review all the reported case studies
regarding the efficacy and safety of adjunctive agents in clozapine-resistant
schizophrenic or schizoaffective patients. All published case studies
examining the efficacy and safety of adjunctive agents in clozapine-resistant
schizophrenic patients were searched for in the MEDLINE database from
January 1980 to February 2004. Case studies regarding ECT as a clozapine
augmentation strategy were not included in our study. All the included
papers were critically reviewed and examined against a set of clinical
and pharmacological parameters, outcome measures, and reported side effects.
Fifteen case studies regarding the efficacy and safety of sulpiride, risperidone,
olanzapine, lithium, lamotrigine, fluvoxamine, and bromocriptine as clozapine
adjuncts were found. A total of 33 schizophrenic or schizoaffective patients
were included. Of the 15 studies, 8 were associated with risperidone.
The duration and dosage of previous clozapine monotherapy was adequate
for 16 patients. Plasma clozapine level was assessed for only 7 patients.
Outcome measures were used for only 11 patients. The outcome was positive
in 13 studies. Combined treatments were generally well tolerated, and
side effects never resulted in discontinuation of treatment. Most case
studies favor the use of risperidone as an adjunctive agent in clozapine-resistant
schizophrenic or schizoaffective patients. However, small numbers of patients
and other methodological shortcomings limit the impact of evidence provided.
