Even with adequate treatment, as
little as 20 percent of patients with schizophrenia
have a complete resolution of symptoms,
whereas up to one third have a clinically
inadequate response.1 Poor response of psychotic
symptoms to single antipsychotic drugs has been
cited as the most common reason for simultaneous
prescription of multiple antipsychotic drugs,
or polypharmacy.2,3 Antipsychotic polypharmacy
is increasingly common, although the evidence
of its efficacy from randomized, controlled trials
is limited or contradictory, there is a risk of exacerbation
of side effects, and the cost implications
are substantial.4-14 If antipsychotic polypharmacy
is of value, treatment with combinations of drugs
with complementary receptor-binding properties
might have the highest likelihood of success.15
Clozapine does not saturate dopamine D2 receptors,
even when given at high doses, whereas risperidone
occupies a high proportion of dopamine
D2 receptors when given at clinically used doses.16
Combining drugs that have complementary profiles
of cognitive improvement might be of further
benefit. Clozapine and risperidone both appear
to improve frontal-lobe function, although
risperidone may have more benefit for verbal working
memory.17
We investigated whether augmentation with
risperidone would alleviate psychotic symptoms
in patients with an incomplete response to treatment
with clozapine at the usual clinical dose over
an appropriate period of time. The secondary
hypotheses were that risperidone augmentation
would improve cognitive functioning and that the
side effects of clozapine plus risperidone would
be similar to those of clozapine alone.