A pilot study to determine whether machine learning methodologies using pre-treatment electroencephalography can predict the symptomatic response to clozapine therapy.

Objective: To investigate whether applying advanced machine learning (ML) methodologies to pre-treatment electroencephalography (EEG) data can predict the response to clozapine therapy in adult subjects suffering from chronic schizophrenia.

Methods: Pre-treatment EEG data are collected in 23+14 schizophrenic adults. Treatment outcome, after at least one year follow-up, is determined using clinical ratings by a trained clinician blind to EEG results. First, a feature selection scheme is employed to select a reduced subset of features extracted from the subjects' EEG that is most statistically relevant to our treatment-response prediction. These features are then entered into a classifier, which is realized in the form of a kernel partial least squares regression method that performs response prediction. Various scales, including the positive and negative syndrome scale (PANSS) are used as treatment-response indicators.

Results: We determined that a set of discriminating EEG features do exist. A low-dimensional representation of the feature space showed significant clustering into clozapine responder and non-responder groups. The minimum level of performance of the proposed prediction methodology, tested over a range of conditions using the leave-one-out cross-validation method using the original 23 subjects, with further testing in an independent sample of 14 subjects, was 85%.

Conclusions: These findings indicate that analysis of pre-treatment EEG data can predict the clinical response to clozapine in treatment resistant schizophrenia.

Significance: If replicated in a larger population, this novel approach to EEG analysis may assist the clinician in determining treatment-efficacy.