Study of concomitant antipsychotic use - Part 1 (only available in French)

05-01-2009 | Médicaments: Usage optimal

Introduction

In 2007, as a follow-up to two investigative reports on schizophrenic patients who passed away while taking combination antipsychotic therapy, the coroner asked the Conseil du médicament to “use the database of the Basic Prescription Drug Insurance Plan to monitor the frequency of prescriptions combining more than one neuroleptic in order to properly document this practice which is contrary to the available evidence.” In response to this request, the Conseil has undertaken a three-part study aimed at documenting the concomitant use of antipsychotics among the general population (part 1), among children and adolescents (part 2), and among adults and seniors (part 3). This document presents part 1.

Current knowledge

Antipsychotics are drugs indicated primarily for the treatment of psychotic disorders such as schizophrenia. There are two different types: typical antipsychotics (also known as first-generation antipsychotics, FGAs) and atypical antipsychotics (second-generation antipsychotics, SGAs). Compared to FGAs, SGAs have fewer side effects such as extrapyramidal side effects (EPSEs) and tardive dyskinesia. Recent studies have shown, however, that SGAs have other severe side effects such as metabolic perturbations and cardiac disorders. For the treatment of psychotic disorders, Canadian and U.S. guidelines stress the general principle that only one antipsychotic should be used at a time. In order to counter non-response and incomplete response to treatment, the guidelines suggest:

  • Optimizing the dosage
  • Ensuring an adequate trial duration
  • Substituting another antipsychotic, and trying a second or third SGA in monotherapy as well as an FGA before using clozapine
  • Trying clozapine
  • Combining clozapine with an SGA or an FGA

To date, the efficacy of combination antipsychotic therapy has not been sufficiently studied. In scientific literature, only a few randomized double-blind studies have documented the efficacy of concomitant antipsychotic use in small cohorts of patients. This practice has nevertheless become increasingly common and is less likely to be reserved for the most severely affected or refractory patients.

For patients diagnosed with schizophrenia or other psychoses that exhibit an incomplete response to monotherapy, certain clinicians may be tempted to believe that the simultaneous use of more than one antipsychotic is an attractive solution that may increase the efficacy of treatment. Insufficient data on the real gains in efficacy that result with antipsychotic combination therapy, however, leads to uncertainties as to the advantages of this type of treatment compared to the risks and costs involved.

Objectives of the study

  1. Determine the prevalence of antipsychotic usage
  2. Categorize antipsychotic users based on type of use: combination therapy and monotherapy, short-term and long-term use
  3. Describe the various combinations of antipsychotics used in combination therapy 

Methods

A retrospective cohort study was conducted with individuals who had ongoing coverage between January 1 and December 31, 2006, under the Public Prescription Drug Insurance Plan administered by the Régie de l’assurance maladie du Québec (RAMQ). All data was anonymized prior to analysis.

Results

The most prevalent use of antipsychotics was reported among employment assistance recipients (12.6%), nearly 3 times higher than among those aged 65 and over (4.5%) and 7 times higher than among those who were employed and covered by the Public Prescription Drug Insurance Plan (1.8%). The observed antipsychotic combinations followed no predetermined model.

Conclusion

Very few randomized double-blind studies support the efficacy and safety of combination antipsychotic therapy. It therefore gives cause for concern that this practice seems relatively common for the treatment of schizophrenia and other psychiatric disorders in Québec and in several countries around the world. Further studies documenting benefits and risks are necessary in order to assist clinicians in making the appropriate decision in cases involving patients deemed refractory to monotherapy.

Based on the results from part 1 of the study, the Conseil du médicament intends to collaborate with the Association des Médecins Psychiatres du Québec, the Collège des médecins and other partners in order to create a decision support tool aimed at facilitating the optimal use of antipsychotics. The results from parts 2 and 3 of this study will help to further direct certain interventions.

 

REF24

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