American Psychiatric Association's Convention Updates|
The first is this one, from the makers of Lexapro... "Forest Laboratories, Inc. (NYSE: FRX) today announced the results of a placebo-controlled study, which showed that severely depressed patients treated with escitalopram oxalate showed significant improvement over placebo beginning as early as week two and continuing throughout the eight-week study period. Patients with severe depression experience a greater number of debilitating symptoms and suffer increased dysfunction at home or in the workplace. The findings were presented at the 156th annual meeting of the American Psychiatric Association (APA) in San Francisco."
Eight weeks, of course, is great to show us side-effects and effects compared with a sugar pill. But most researchers consider the time period very minimal and not at all replicating real-world prescriptions of these medications (which is much more likely to be prescribed 8 months or 8 years!). How does it compare with similar medications for the same disorder? Well, this study didn't look at that, so we don't know yet.
Out of the University of Pennsylvania, comes this information...
"Studies presented at the 156th annual meeting of the American Psychiatric Association (APA) examined the use of an atypical antipsychotic as both monotherapy and adjunct therapy to mood stabilizer for the acute manic phase of bipolar disorder. Results showed:
- Greater response rates than placebo
- Higher remission rates than placebo, with a majority of responsive patients achieving remission – defined as the full resolution of manic symptoms
- Fewer side effects than traditional anti-psychotics and other atypicals"
Good news for folks looking for new treatments in bipolar disorder, but the studies suffer from the same short study time-frame and lack direct comparison with other widely-available medications for treatment of this disorder. But any medication that has fewer side effects than those presently available is usually a good thing.
Last, from Eli Lilly, we have the following...
"One study is an analysis of treatment-emergent mania with Olanzapine and Olanzapine/Fluoxetine combination, and the study showed that both Zyprexa and Symbyax, an investigational drug that combines Zyprexa with Prozac, help patients effectively battle bipolar depression within the first week of treatment. Other data demonstrated that patients treated with Symbyax were no more likely to develop treatment-emergent mania than patients receiving placebo or Zyprexa alone. Manic episodes are often a
potential consequence of treatment with an antidepressant medication."
"The second announcement is the Schizophrenia Outpatient Health Outcomes (SOHO) study, which consists of two three-year studies, SOHO EU (approximately 10,000) patients and SOHO IC (8,600 patients). This study is significant in that it is unprecedented in size and scope, including more
than 18,600 patients in 37 countries. Patients in the study treated with Zyprexa, or olanzapine, had greater
symptom improvement and social functioning compared with patients on other leading schizophrenia medications."
This second study is the most interesting of the bunch, because of its time-frame (6 months into a 3 year study) and size (18,600 subjects). These are nice, robust numbers that researchers love to see but rarely do because of the enormous costs associated with running a study of this size. It's good to see that Zyprexa is doing well in this study. I've included the full Eli Lilly press release below because it has some very interesting tidbits and findings so far:
Six-month findings from the world's largest observational schizophrenia study show that although patients treated with atypical antipsychotics experienced marked improvement in their quality of life, various treatments differed in terms of effectiveness, sometimes significantly. People treated with olanzapine had greater symptom improvement and social functioning compared with patients on other leading schizophrenia medications, researchers reported today at the annual meeting of the American Psychiatric Association.
Unlike a traditional clinical trial, the Schizophrenia Outpatient Health Outcomes (SOHO) study will collect scientifically robust, long-term data in "real-world" settings. Eli Lilly and Company is sponsoring two three-year studies, one in Western Europe (SOHO EU) that includes 10 countries and approximately 10,000 patients. The second study is being conducted in Asia, Central and Eastern Europe, Latin America and the Middle East (SOHO IC) and includes 27 countries and 8,600 patients. With more than 18,600 patients enrolled from 37 countries, SOHO is unprecedented in size and scope.
Six Month Key Findings
In SOHO EU research, patients on olanzapine had significantly greater improvement in positive (delusions and hallucinations), negative (diminished emotion, lack of interest), depressive, cognitive and overall symptoms and social functioning compared with patients on risperidone, quetiapine, oral typical and depot typical antipsychotics. No significant differences were found between olanzapine and clozapine.
Of the 10,204 patients included at the start of the SOHO EU study, 9,028 (88.5%) were still in the trial six months later. This is an exceptionally high retention rate for a study evaluating treatments in people with schizophrenia, as this population is prone to medication compliance problems.
Greater than 35 percent of patients in the SOHO EU study on risperidone and typical antipsychotics were taking anticholinergic agents (medication to control tremors or other movement disorders) or experiencing movement disorders after the first six months of treatment. This is compared with 20 percent or fewer patients treated with olanzapine or clozapine.
Using a questionnaire specific to Germany, a subanalysis of German outpatients with schizophrenia (n = 2,450) suggests that after six months of treatment patients prescribed atypical antipsychotics experienced strong improvements in quality of life, including subscores reflecting self-control, physical and mental functioning, emotional regulation and social interaction.
Another analysis that specifically looked at SOHO IC patients on either olanzapine or quetiapine (n = 7,655) found that patients treated with olanzapine showed greater improvement in clinical status and social functioning compared to those treated with quetiapine.
In a SOHO IC analysis (n=501) of neuroleptic naïve patients with schizophrenia, 19 percent of patients treated with risperidone and 30 percent of patients treated with haloperidol developed impotence/sexual dysfunction compared to three percent of olanzapine-treated patients.
Across treatment categories, results from measurements collected by study investigators at six months are consistent with results obtained from questionnaires completed directly by the patients in the study.
"SOHO has yielded important information about the care we provide people with schizophrenia and the real-world outcomes of that care," said Dr. William M. Glazer, Associate Clinical Professor of Psychiatry, Massachusetts General Hospital, Harvard Medical School. "This kind of naturalistic study complements the data of more traditional clinical trials. Rigid exclusion criteria in conventional studies can limit our ability to reflect the patient population we see everyday."
Glazer continued, "Despite the vast differences in health care systems and cultures across the 10 European Union countries, there is marked consistency in the results. This validates the study's design and also reflects the clinical utility of agents such as olanzapine."
Patients were enrolled in the study if, at the discretion of the treating psychiatrist, they started or changed antipsychotic medication in the outpatient setting. There are two study groups: patients who started the study with, or changed to, olanzapine and those who started the study with or changed to another antipsychotic such as amisulpride, quetiapine, risperidone, an oral typical, depot typical or a combination of these medications.
Mean change in positive, negative, depressive, and overall symptoms from baseline to six months was measured using the Clinical Global Impressions-Schizophrenia scale (CGI-S).
The SOHO study will look at more than 30 areas over the course of three years to assess how treatment patterns affect patients' living conditions, clinical status, health-related quality of life, and ability to work and socialize. It will also assess treatment tolerability, compliance, victimization, violence and resource use.
Schizophrenia is a severe and debilitating psychosis often characterized by acute episodes of delusions (false beliefs that cannot be corrected by reason), hallucinations (usually in the form of non-existent voices) and long-term impairments such as diminished emotion, lack of interest and depressive signs and symptoms. It is usually associated with a disruption in social and family relationships.
Schizophrenia is the most common severe mental illness. There are as many as 50 million people with schizophrenia worldwide, more than 33 million of them in developing countries. Symptoms of schizophrenia usually begin to appear in the teenage years or early to mid-twenties.
Olanzapine is indicated in the United States for the treatment of schizophrenia, the short-term treatment of acute manic episodes associated with bipolar disorder and for the long-term therapy and maintenance of treatment response of schizophrenia. Olanzapine was the first atypical antipsychotic to prove its long-term effectiveness in patients with schizophrenia. Since olanzapine was introduced in 1996, it has been prescribed to 11 million people worldwide.
In the original schizophrenia registration trials, olanzapine was generally well tolerated. However, as with all medications, olanzapine was associated with some side effects. In the original six-week, acute-phase schizophrenia trials, the most common treatment-emergent adverse event associated with olanzapine was somnolence. Other common events were dizziness, weight gain, constipation, akathisia (inner and outer restlessness) and postural hypotension. Modest elevations of prolactin were also seen, although mean changes from baseline to endpoint were not statistically significantly different between olanzapine and placebo. A small number of patients experienced asymptomatic elevations of hepatic transaminase; none of these patients developed jaundice or drug-induced hepatitis.
In short-term (three- and four-week) acute bipolar mania trials, the most common treatment-emergent adverse event associated with olanzapine was somnolence. Other common events were dry mouth, dizziness, asthenia (muscle weakness), constipation, dyspepsia, increased appetite, and tremor.