Strategies for Switching From Conventional Antipsychotic Drugs or Risperidone to Olanzapine

Background: This study compared the efficacy andsafety of 4 therapeutically relevant strategies for switchingclinically stable patients from a conventional antipsychotic drugor risperidone to olanzapine.

Method: Two hundred nine outpatients with aDSM-IV diagnosis of schizophrenia or schizoaffective disorder whowere clinically stable while being treated with a conventionalantipsychotic drug or risperidone were openly randomly assignedto either abrupt or gradual discontinuation of their priorantipsychotic drug. Patients were further randomly assigned in adouble-blind fashion to immediate olanzapine initiation(olanzapine, 10 mg q.d. for 3 weeks) or stepwise initiation (asequence of 1 week each on placebo; olanzapine, 5 mg q.d.; andolanzapine, 10 mg q.d.). The efficacy of these 4 switchingparadigms 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 extrapyramidalsymptoms, cognitive impairment, adverse events, laboratoryparameters, weight change, and vital signs.

Results: The paradigm of gradual antipsychoticdrug discontinuation combined with an initial full dose ofolanzapine, 10 mg/day, had the most favorable efficacy andtolerability profile overall. By week 3, the majority ofcompleting patients on all 4 switching paradigms were eitherimproved or clinically unchanged (>= 90%). No clinicallysignificant differences between switching paradigms were seen inlaboratory values or vital signs.

Conclusion: In this study, switching clinicallystable outpatients with a diagnosis of schizophrenia orschizoaffective disorder to olanzapine was most successful when afull therapeutic dose of olanzapine was immediately initiatedwhile gradually discontinuing prior conventional antipsychoticdrug or risperidone treatment. Overall, switching was achievedwithout increased vulnerability to relapse or to occurrence ofclinically burdensome antipsychotic drug withdrawal symptoms inthe majority of patients.