STM Article Repository

A large proportion of patients with treatment-resistant schizophrenia continue to have persistent
symptoms and psychosocial impairment despite adequate treatment with clozapine. This group of
patients with clozapine resistant schizophrenia (CRS) constitutes about 40%-70% of those with
treatment-resistant schizophrenia. These patients represent the most severely ill among those with
schizophrenia with higher levels of symptom severity and disability, and greater socioeconomic
burden. A large body of evidence has shown that when clozapine fails, augmentation of its response
with antipsychotics or other medications is of little or no benefit for these patients. Augmentation with
electroconvulsive therapy seems to hold some promise, but the evidence is limited. The benefits of
psychosocial interventions in augmenting clozapine response in these situations has not been
explored fully. A few trials of cognitive-behavioural therapy (CBT) have been undertaken, and their
results do not seem to support the effectiveness of adjunctive psychosocial therapies in augmenting
the efficacy of clozapine in these patients. Nevertheless, this chapter attempts to re-evaluate the
evidence for the effectiveness of psychosocial interventions in CRS, by conducting a brief review of
the area followed by illustrative histories of patients with CRS who benefitted from adjunctive
psychosocial therapies. The results suggest that adjunctive psychosocial treatments could still have a
role in potentiating clozapine response in CRS. However, psychosocial treatment modules that
combine CBT with other treatment strategies such as individual support, stress management, and
family interventions are more likely to be successful in augmenting clozapine response in CRS than
CBT alone. Therefore, there is much scope for further research in this area.