Therapeutic antagonism between anticholinergics and neuroleptics: possible involvement of cholinergic mechanisms in schizophrenia.

We have answered technical criticisms of our work in which anticholinergic agents were added to ongoing neuroleptic treatment in an ABA' research design. The suggested analysis of variance for repeated measures of the three periods is inappropriate because of the expected carryover effects from continuous neuroleptic treatment. The multivariate analysis of various parameters seems unsuitable because homogeneity of covariance cannot be ensured due to the heterogeneity of schizophrenia and the diverse factors represented in the psychopathology measures. We have summarized the results of recent parametric and nonparametric analyses of combined data from our three studies to show that the significant effects clearly pointed to therapeutic antagonism between anticholinergic agents and neuroleptics. We suggest that cholinergic neurons may be part of some crucial discriminative control mechanisms in the brain organization that are ineffective in schizophrenia and lead to a relative overactivity of the opposing catecholaminergic neurons in the midbrain-limbic circuitry which promote repetition of behaviors in goal-directed activity.