Prescribing Pathways to Clozapine Co-Therapy with Antipsychotics.


A. Baines, L. Young, C. Robertson, D. Attwood

Clozapine remains the medication of choice for schizophrenia not responsive to monotherapy. Ineffective clozapine trials appear to lead to combination therapy, though evidence is limited, leaving clinicians with minimal options for this most challenging population.

We used a custom-generated multiple-choice questionnaire with open-ended follow-up questions with physicians prescribing clozapine with at least one additional antipsychotic at The Royal Ottawa Mental Health Centre Schizophrenia Program to capture specific rationales for antipsychotic co-prescription with clozapine.

Nine physicians were interviewed. Surveys were completed for 104 of 285 clients on clozapine, of whom, 136 (47.7%) were on 1-3 additional antipsychotics. The most common reason for clozapine antipsychotic polypharmacy was ‘reduction of positive symptoms’, followed by ‘reduction of negative symptoms’, ‘reduction of affective symptoms’ and ‘management of concurrent symptoms’. Reasons for co-prescription were highly varied with 17 different motives provided. Preferred combination strategies were highly idiosyncratic. Aripiprazole, oral or injectable, was most often cited by 6 out of 9 physicians. Physicians described their assessment of clozapine polypharmacy as ‘improved’ in 76 cases. Ratings on the CGI-I showed; 17 ‘very much improved,’ 40 ‘much improved,’ 49 ‘minimally improved,’ 22 ‘no change.’

In keeping with other studies, antipsychotic co-prescription was most commonly initiated for poorly controlled positive symptoms. Aripiprazole was a frequent choice; however, strategies were highly individual, and no clear guidance on a second antipsychotic is possible from this data. Prospective ratings may better demonstrate efficacy.

Our results emphasize that even in the hands of skilled practitioners, treatment refractory schizophrenia is a highly morbid illness in dire need of innovative and evidence-based guidance to reduce suffering and improve outcomes.

Clinicians Researchers