Better Options for Treatment Resistant Schizophrenia

Research on the comparative effectiveness of antipsychotic medications.

In real-world settings, patients with schizophrenia whose symptoms do not respond to standard antipsychotic medications have better outcomes if they are switched to clozapine instead of another standard antipsychotic. They have fewer hospitalizations, stay on the new medication longer, and are less likely to need to use additional antipsychotics. These findings were published today in the American Journal of Psychiatry.

Schizophrenia is a serious mental disorder affecting up to one percent of the adult population. Antipsychotics are effective at relieving symptoms for most patients, but up to 30% do not respond well to standard treatments and are considered to have treatment-resistant schizophrenia. While trials have indicated that clozapine is effective for these cases, the effectiveness of clozapine in clinical practice has not previously been studied in depth.

Often when one traditional antipsychotic medication does not work, clinicians change to another traditional antipsychotic. Clozapine is often seen as a drug of last resort, although it is the only medication approved by the FDA for treatment-resistant schizophrenia.

The new study was conducted using national Medicaid data from 6,246 patients whose treatment patterns were consistent with treatment resistance. It is the largest study directly comparing the effectiveness of clozapine with standard antipsychotics in this population in routine practice settings.

The results are encouraging and timely because the FDA recently broadened access to clozapine. In the past access was limited, in part because of the risk of agranulocytosis, a condition that can make people susceptible to infections. A system has been in place for 25 years to successfully manage the risks of agranulocytosis, using regular monitoring of white blood cell levels. Leading clinicians thus believe the limits on use of clozapine have been overly restrictive. The new FDA rules still require regular blood monitoring, but allow prescribers to make decisions based on benefits and risks for individual patients rather than rigidly following universal standards.

Image of a woman holding her head in her hands.

Schizophrenia is a serious mental disorder affecting up to one percent of the adult population. Antipsychotics are effective at relieving symptoms for most patients, but up to 30% do not respond well to standard treatments and are considered to have treatment-resistant schizophrenia. Image is for illustrative purposes only.

“These results give clinicians important guidance for how to help an extremely vulnerable group of people,” said T. Scott Stroup, MD, lead author of the study, and professor of psychiatry at Columbia University Medical Center and a research psychiatrist at New York State Psychiatric Institute. “By helping individuals with treatment-resistant schizophrenia get effective treatment sooner we can expect better outcomes.”

About this neuroscience research

Funding: Funding for this study was provided by the Agency for Healthcare Research and Quality.

Dr. Stroup serves as an investigator in a study sponsored by Auspex Pharmaceuticals; and he has participated in CME activities sponsored by Genentech. Dr. Gerhard serves on an external safety review committee for a Merck study; he has provided expert consultation to a law firm on behalf of Roche; and he has received compensation from Boehringer for a talk at an internal CER symposium. Dr. Olfson serves as principal investigator on a grant to Columbia University from Sunovion Pharmaceuticals. All other authors report no financial relationships with commercial interests.

Source: Rachel Yarmolinsky – Columbia University Medical Center
Image Source: The image is in the public domain
Original Research: Abstract for “Comparative Effectiveness of Clozapine and Standard Antipsychotic Treatment in Adults With Schizophrenia” by T. Scott Stroup, Tobias Gerhard, Stephen Crystal, Cecilia Huang, and Mark Olfson in American Journal of Psychiatry. Published online November 2015 doi:10.1176/appi.ajp.2015.15030332


Abstract

Comparative Effectiveness of Clozapine and Standard Antipsychotic Treatment in Adults With Schizophrenia

Objective:
The authors compared the effectiveness of initiating treatment with either clozapine or a standard antipsychotic among adults with evidence of treatment-resistant schizophrenia in routine clinical practice.

Method:
U.S. national Medicaid data from 2001 to 2009 were used to examine treatment outcomes in a cohort of patients with schizophrenia and evidence of treatment resistance that initiated clozapine (N=3,123) and in a propensity score-matched cohort that initiated a standard antipsychotic (N=3,123). Interventions were new initiation of clozapine or a standard antipsychotic medication, defined as no exposure to the new medication in the prior 365 days. The primary outcome was hospital admission for a mental disorder. Secondary outcomes included discontinuation of the index antipsychotic, use of an additional antipsychotic, incidence of serious medical conditions, and mortality.

Results:
Initiation of clozapine was associated with a significantly decreased rate of psychiatric hospital admission (hazard ratio=0.78, 95% CI=0.69–0.88), index antipsychotic discontinuation (hazard ratio=0.60, 95% CI=0.55–0.65), and use of an additional antipsychotic (hazard ratio=0.76, 95% CI=0.70–0.82). Clozapine was associated with significantly increased incidence of diabetes mellitus (2.8% for clozapine vs. 1.4% for standard antipsychotic; hazard ratio=1.63, 95% CI=0.98–2.70), hyperlipidemia (12.9% for clozapine vs. 8.5% for standard antipsychotic; hazard ratio=1.40, 95%CI=1.09–1.78), and intestinal obstruction (0.9% for clozapine vs. 0.3% for standard antipsychotic; hazard ratio=2.50, 95% CI=0.97–6.44).

Conclusions:
In adults with schizophrenia and evidence of treatment resistance, initiating clozapine compared with initiating a standard antipsychotic was associated with greater effectiveness on several important outcomes. Increasing the judicious use of clozapine is warranted together with vigilance to prevent and detect serious medical adverse effects.

“Comparative Effectiveness of Clozapine and Standard Antipsychotic Treatment in Adults With Schizophrenia” by T. Scott Stroup, Tobias Gerhard, Stephen Crystal, Cecilia Huang, and Mark Olfson in American Journal of Psychiatry. Published online November 2015 doi:10.1176/appi.ajp.2015.15030332

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