Treatment response of neurological soft signs in drug-naïve patients with a first psychotic episode

Background: Neurological soft signs (NSS) are intrinsic features of psychosis that appear years before beginning a drug treatment. However, whether NSS respond to antipsychotics and whether these changes are clinically reliable and significant remains to be seen.

Objective: We sought to determine the effect of antipsychotics on NSS in a first-episode psychosis (FEP) sample who had never exposed to antipsychotics.

Methods: We included 100 antipsychotic-naïve patients with FEP in this study. 77 patients completed the study assessments at baseline, 1 month and 6 months. The Neurological Evaluation Scale (NES) evaluated NSS. Patients were alternatively selected to receive risperidone or olanzapine treatments and continued participation in their mental health setting during follow-up with one of four treatment groups: risperidone, olanzapine, mixed antipsychotics or no medication. We also included a control group of 28 healthy volunteers.

Results: Treatment groups showed a statistically significant improvement on total NES scores and most NES subscales except for 'frontal signs', regardless of antipsychotic allocation. NSS changes were reliable; however, there was great variation in the total NES scores between treatment groups, ranging from 4% to 24%. Clinically meaningful changes (CMCs) on total NES scores ranged from 25% to 50%. Six patients (7.8%) demonstrated a reliable change (RC) and CMC on total NES scores.

Conclusions: NSS improved significantly over follow up regardless of the treatment regimen assigned to antipsychotic-naïve patients with a FEP. However, only 6 (7.8%) achieved a reliable and clinically meaningful improvement. The pattern of response of NSS to antipsychotic drugs evidenced both state and trait characteristics.