Abstract
BackgroundClozapine is the treatment of choice for medication refractory psychosis, but it does not benefit half of those put on it. There are numerous studies of potential post-clozapine strategies, but little data to guide the order of such treatment in this common clinical challenge. We describe a naturalistic observational study in 153 patients treated by a specialist psychosis service to identify optimal pharmacotherapy practice, based on outcomes.MethodsMedication and clinical data, based on the OPCRIT tool, were examined on admission and discharge from the national psychosis service. The primary outcome measure was the percentage change in mental state examination symptoms between admission and discharge and the association with medication on discharge. Exploratory analyses evaluated the specificity of individual medication effects on symptom clusters.ResultsThere were fewer drugs prescribed at discharge relative to admission, suggesting an optimisation of medication, and a doubling of the number of patients treated with clozapine. Treatment with clozapine on discharge was associated with maximal decrease in symptoms from admission. In the group of patients that did not respond to clozapine monotherapy, the most effective drug combinations were clozapine augmentation with 1) sodium valproate, 2) lithium, 3) amisulpride, and 4) quetiapine. There was no support for a dose–response relationship for any drug combination.ConclusionsClozapine monotherapy is clearly the optimal medication in medication refractory schizophrenia and it is possible to maximise its use. In patients unresponsive to clozapine monotherapy, augmentation with sodium valproate, lithium, amisulpride and quetiapine, in that order, is a reasonable treatment algorithm. Reducing the number of ineffective drugs is possible without a detrimental effect on symptoms. Exploratory data indicated that clozapine was beneficial across a range of symptoms domains, whereas olanzapine was beneficial specifically for hallucinations and lamotrigine for comorbid affective symptoms.
Highlights
Clozapine is the treatment of choice for medication refractory psychosis, but it does not benefit half of those put on it
Aim We describe a naturalistic study of outcomes in 153 treatment refractory inpatients on a specialist tertiary psychosis service, the National Psychosis Service (NPS) at the Maudsley and Bethlem Royal Hospitals, London, UK
The methodology of data collection is described in our earlier work [20], but in brief, clinical notes of patients admitted to the NPS between 2001 and 2007 were collated and retrospective analysed using the OPCRIT system
Summary
Clozapine is the treatment of choice for medication refractory psychosis, but it does not benefit half of those put on it. There are numerous studies of potential post-clozapine strategies, but little data to guide the order of such treatment in this common clinical challenge. Clinical outcomes in schizophrenia are often disappointing: a third of patients are resistant to standard pharmacological interventions [1], fewer than one in eight individuals fully recover [2], and data are disheartening for negative and cognitive symptoms [3]. Clozapine is the most effective antipsychotic for more treatment naïve [4] and medication refractory patients [5], but half will not show significant improvement on. Three critical issues occur in the “post-clozapine” literature: study methodologies; heterogeneity of psychosis outcomes; and a medication accumulation bias. Remission often does not occur and such polypharmacy is more likely to become the rule rather than the exception
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