Effects of Typical and Atypical Antipsychotics on the Prepulse Inhibition of the Startle Reflex in Patients With Schizophrenia

Abstract

Patients with schizophrenia show a loss of sensory (motor) gating, which is reflected in a reduced prepulse inhibition (PPI) of the startle reflex. Furthermore, patients with schizophrenia habituate less than healthy subjects. From previous studies, it is clear that typical antipsychotics have little or no effect on either sensorimotor gating or habituation, while only limited data is available on the effects of atypical antipsychotics on these processes.Forty-four schizophrenic patients (27 stable on typical and 17 stable on atypical antipsychotics) and 35 healthy control subjects were tested in a PPI paradigm. The prepulse and startle stimuli were pure tones of 1500 Hz (duration 40 ms, intensity 80 dB and 110 dB respectively), with a fixed interstimulus interval of 120 milliseconds. Block effects in PPI and startle amplitude to the pulse alone trials (habituation) were analyzed over the three groups, using comedication (i.e., benzodiazepines) as a covariate. Main effect for block was found for startle amplitude (habituation), while main effects for group and block were found for percentage PPI. Further analysis displayed significant differences in PPI between the patients treated with typical antipsychotics and the healthy control group, while patients treated with atypical antipsychotics did not differ from either the healthy control group, or the patients treated with typical antipsychotics. Furthermore, post-hoc division of the patients treated with atypical antipsychotics in patients treated with clozapine and risperidone revealed that this superiority from atypical antipsychotics over typical antipsychotics appeared to be mainly based on the effects of clozapine. Patients with schizophrenia who are treated with atypical antipsychotics appear to have levels of sensorimotor gating that are more consistent with healthy controls than patients who are treated with typical antipsychotics. Furthermore, within the class of atypical antipsychotics, clozapine appears most potent in restoring this process.

Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels

“…Thus, it appears that stratification of normal subjects into low and high PPI performers did not reveal the predicted enhancement of PPI by haloperidol in normal subjects with relatively low PPI levels. This negative finding is in accordance with several studies in schizophrenia patients, which showed that atypical antipsychotic medication had no PPI-enhancing effect (Grillon et al, 1992;Kumari et al, 1999;Oranje et al, 2002b;Duncan et al, 2003a, b;Perry et al, 2002;Mackeprang et al, 2002). It should be noted that the healthy subjects in our earlier study (Vollenweider et al, 2006) had lower PPI levels (mean SOA60 ¼ 8.873.3%) than did the low PPI group in the present study (mean SOA60 ¼ 43.8713.8%).…”

“…Results of a number of cross-sectional studies suggest that patients treated for schizophrenia with atypical antipsychotics have similar PPI values as normal controls (Kumari et al, 1999(Kumari et al, , 2000Leumann et al, 2002;Oranje et al, 2002b), whereas those treated with typical antipsychotics exhibited less PPI than the control subjects (Grillon et al, 1992;Kumari et al, 1999;Oranje et al, 2002b). However, another study failed to replicate this distinction, finding that typical and atypical medications were equipotent in reversing the PPI deficit in schizophrenia patients (Quednow et al, 2005).…”

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

“…Furthermore, both typical and atypical antipsychotics have been tested in several clinical studies: Kumari et al (1999) reported normal PPI in schizophrenic patients treated with the atypical antipsychotic clozapine, when compared with healthy controls, whereas patients treated with typical antipsychotics showed reduced PPI. This has been replicated by Oranje et al (2002b); (for a review, see . In contrast to clozapine, Duncan et al (2003a) found that patients treated with olanzapine had levels of PPI comparable to patients treated with haloperidol or patients who are not treated at all, whereas this group as a whole showed significantly less PPI compared with healthy controls.…”

Effects of olanzapine, risperidone and haloperidol on prepulse inhibition in schizophrenia patients: A double-blind, randomized controlled trial

“…Several between subject, non-prospective studies of the effects of antipsychotic medications on PPI in schizophrenia revealed that patients treated with atypical medications have higher levels of PPI compared to those treated with conventional medications (Kumari et al, 1999(Kumari et al, , 2000(Kumari et al, , 2002Leumann et al, 2002;Oranje et al, 2002). However, some studies have failed to show that either atypical or conventional antipsychotic medications are lawfully associated with PPI in schizophrenia patients (Duncan et al, 2003).…”