Risperidone augmentation of clozapine

While effective as a single agent in a significant proportion of treatment refractory patients, clozapine is often used in combination with other medications, including classical neuroleptics (1), mood stabilizers and antidepressants (2), benzodiazepines (3) and lithium (4). In Denmark, where clozapine has been in near continuous use since 1975, up to 60% of clozapine patients receive additional medication (4). Classical neuroleptics, often at antipsychotic levels, are the medications most frequently added, and are used in 30-35% of patients receiving clozapine (4,5). Clozapine, due to its low D2-blocking effect, may be therapeutically insufficient to contain symptoms and additional agents may be required (4). In controlled clinical trials risperidone has been shown to be superior to haloperidol (6), but has not yet been rigorously compared to clozapine. In light of its established efficacy and pharmacological profile (7) risperidone may be reasonably construed to be a medication with efficacy somewhere between clozapine and classical neuroleptics. As such, it may be especially well suited for use with clozapine as a part of an augmentation strategy. There are no reports in the literature describing the concurrent use of risperidone and clozapine. We present two cases demonstrating augmentation of clozapine's effects through combined use with clozapine.