Clozapine is Better than Standard Antipsychotics for Reducing Schizophrenia Hospitalizations but has Greater Health Risks

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

Am J Psychiatry. 2015 Nov 6;:appiajp201515030332

Authors: Stroup TS, Gerhard T, Crystal S, Huang C, Olfson M

Abstract

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.

PMID: 26541815

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NOTE: the primary measure is the frequency of hospitalizations.  

The study did not attempt to determine if a person is more FUNCTIONAL on Clozaril than on the other medications. This is a significant limitation of this study.  

For example, other antipsychotics in stable patients may help the patient be more functional in the community.  Clozaril may be so oversedating and cognitively impairing that patients become totally disabled but docile on it.   In this case, the cure may be as bad as the illness. 

 

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