Nonresponse to clozapine and premorbid functioning in treatment of refractory schizophrenia.

Introduction: It is recognized that early treatment can improve outcomes and generally improve recovery potential for those with schizophrenia. Data suggest that poor premorbid functioning has been found to be related to more severe symptoms and poor antipsychotic response; however, little is known about premorbid functioning in patients who have no response to clozapine treatment.

Methods: This study compares the premorbid functioning among patients who responded to clozapine treatment (20% decrease in total Brief Psychiatric Rating Scale [BPRS] score; n = 35) and those who did not respond (n = 50) to 8 weeks of clozapine treatment. Premorbid functioning was assessed using the Cannon-Spoor Premorbid Adjustment Scale.

Results: Patients who did not respond to clozapine had significantly lower total BPRS scores (P = .01) at baseline, driven primarily by lower ratings in hostility (P = .007) and activation (P = .02), compared with those who responded to clozapine. Responders and nonresponders did not differ in their age, race, level of education, marital status, age of onset, characterization of the deficit syndrome, and positive or negative symptoms. Nonresponders to clozapine did not improve in any area of symptoms or global functioning, whereas there were significant improvements in BPRS total scores (analysis of covariance) and all symptom domains in the responder groups (P < .0001). Level of functioning scores in those who responded to clozapine was significantly higher at end point (P = .02). As for premorbid functioning, there were no differences in scores between responders and nonresponders at the time of early and late adolescence; however, there was a trend toward lower premorbid functioning in the clozapine nonresponders on most childhood measures (before the age of 11 years). Clozapine nonresponders tended to be less social and more withdrawn as compared with those who responded to clozapine (P = .08), as well as tended to have poorer adaptation to school (P = .06) and fewer peer relationships (P = .08). These results did not reach significance. Work and/or school performance changed more insidiously in the nonresponders group before illness onset (P = .045).

Discussion: Clozapine is beneficial to many patients with treatment-resistant symptoms; however, nonresponse to this medication may represent a subtype of patients who may present differently with symptoms. These findings should encourage further examination of early childhood indicators and opportunities for appropriate and effective intervention.