Q: At what point does a patient with schizophrenia have a “treatment-refractory” illness? If he or she does, when is it best to use clozapine as the treatment of choice for this type of schizophrenia?
A: The second question can’t be addressed without being clear about the first component. In practice, this can be very complicated.
First, you must confirm that the inadequate treatment response that you see for any given treatment is not merely the expression of partial (or even complete) medication nonadherence. This of itself is a major topic, and to detail how best to do this is beyond the scope of this brief communication. Nevertheless, it is a fundamental consideration.
Second, you need to confirm that the patient has received an “adequate trial” of 2 or more antipsychotic medications. What constitutes an adequate trial? It is crucial that the patient has been taking the given drug long enough (typically considered about 8 weeks) and at an appropri-ate dosage (not necessarily the highest dosage, but at least enough to be therapeutically effective for the majority of patients). It is also important to consider comorbidities, both psychiatric (eg, developmental disabilities) and medical (eg, thyroid disorder), that can complicate the clinical picture and reduce the likelihood of treatment success with any medication.
Finally, there are, of course, many social and personal factors that can contribute to an inadequate treatment response. This leads to the second question—namely, when to use clozapine. Clozapine is not a first-line treatment. Indeed, there is evidence that it is only about as effective as other medications when given early in the illness, especially in patients who might otherwise already be considered more responsive to treatment. On the other hand, it is not the treatment of last resort.
Clozapine should not be reserved for use until everything else has been tried and has failed. This is particularly important nowadays. With so many antipsychotic medications to choose from, a patient with a bad illness who would be a candidate for clozapine could have to endure successive trials of multiple equiefficacious antipsychotics. This hardly seems logical. Thus, clozapine should be considered as a primary treatment if and when it has been clearly established that the patient has treatment-refractory schizophrenia.
The various treatment guidelines are a useful authoritative resource for the reader who wants to know more about this topic. In addition, Drs Helio Elkis and Herbert Meltzer1— both renowned experts on the treatment of schizophrenia—have just published a remarkably comprehensive book on this topic.
1. Elkis H, Meltzer HY, eds. Therapy-resistant schizophrenia. Adv Biol Psychiatry. Basel, Switzerland: Karger; 2010;26:114-128.