Auditory P50 in schizophrenics on clozapine: Improved gating parallels clinical improvement and changes in plasma 3-methoxy-4-hydroxyphenylglycol

Schizophrenic patients have decreased inhibition of the P50 auditory evoked potential response to the second of two paired click stimuli delivered 500 ms apart. This deficit in inhibitory gating does not change during treatme nt with typical neuroleptics. We recently reported that neuroleptic-resista nt schizophrenics had enhanced P50 gating after 1 month of clozapine treatm ent, if they responded with decreased clinical symptoms. This study reports the outcome of more prolonged treatment. Ten treatment-refractory schizoph renic patients were studied at baseline, after 1 month on clozapine, and ag ain after 15 +/- 6.1 (SD) months of clozapine treatment. Eight subjects rea ched a clinically stable improved state, at which time they had significant ly improved P50 auditory gating. One patient had a return of impaired gatin g after stopping clozapine, as did another during a clinical relapse. Decre asing plasma 3-methoxy-4-hydroxyphenylglycol levels with clozapine treatmen t were correlated with improved P50 gating and improved Brief Bsychiatric R ating Scale-positive scores. This study provides further evidence that impr oved P50 gating in schizophrenic patients treated with clozapine coincides with clinical improvement and that this improvement can be sustained for at least 1 year.