Strategies for Switching From Conventional Antipsychotic Drugs or Risperidone to Olanzapine
J Clin Psychiatry 2000;61:833-840
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Background: This study compared the efficacy and
safety of 4 therapeutically relevant strategies for switching
clinically stable patients from a conventional antipsychotic drug
or risperidone to olanzapine.
Method: Two hundred nine outpatients with a
DSM-IV diagnosis of schizophrenia or schizoaffective disorder who
were clinically stable while being treated with a conventional
antipsychotic drug or risperidone were openly randomly assigned
to either abrupt or gradual discontinuation of their prior
antipsychotic drug. Patients were further randomly assigned in a
double-blind fashion to immediate olanzapine initiation
(olanzapine, 10 mg q.d. for 3 weeks) or stepwise initiation (a
sequence of 1 week each on placebo; olanzapine, 5 mg q.d.; and
olanzapine, 10 mg q.d.). The efficacy of these 4 switching
paradigms was assessed using the Clinical Global Impressions
(CGI)-Improvement scale, Patient's Global Impressions
(PGI)-Improvement scale, and Positive and Negative Syndrome Scale
(PANSS). Safety assessments included ratings for extrapyramidal
symptoms, cognitive impairment, adverse events, laboratory
parameters, weight change, and vital signs.
Results: The paradigm of gradual antipsychotic
drug discontinuation combined with an initial full dose of
olanzapine, 10 mg/day, had the most favorable efficacy and
tolerability profile overall. By week 3, the majority of
completing patients on all 4 switching paradigms were either
improved or clinically unchanged (>= 90%). No clinically
significant differences between switching paradigms were seen in
laboratory values or vital signs.
Conclusion: In this study, switching clinically
stable outpatients with a diagnosis of schizophrenia or
schizoaffective disorder to olanzapine was most successful when a
full therapeutic dose of olanzapine was immediately initiated
while gradually discontinuing prior conventional antipsychotic
drug or risperidone treatment. Overall, switching was achieved
without increased vulnerability to relapse or to occurrence of
clinically burdensome antipsychotic drug withdrawal symptoms in
the majority of patients.