The effects of imipramine on P50 suppression, prepulse inhibition and habituation of the startle response in humans

Schizophrenic patients exhibit impairments in filtering of sensory information, as can be assessed by use of prepulse inhibition (PPI) of the acoustic startle response and P50 suppression paradigms. In the treatment of negative symptoms or depressive syndromes during the course of schizophrenia antidepressants are often combined with antipsychotic medication. However, antidepressants increase monoaminergic activity, which has been suggested to decrease sensory gating, although these presumptions are mostly based on results from animal studies. Currently, little is known about monoaminergic modulation of sensory filtering in humans, and the few reports that can be found in literature show discrepancies with animal studies. The current study was designed to study the effects of increased monoaminergic activity on sensory filtering and habituation of healthy volunteers. In a double-blind, placebo-controlled crossover design, 20 healthy male Volunteers received either placebo or a dose of 50 mg imipramine (a dual-acting antidepressant), after which they were tested in a P50 suppression paradigm, a PPI paradigm, and an habituation of the startle reflex paradigm. Imipramine significantly decreased PPI as well as P50 suppression. No significant differences between the two treatments were observed on habituation of the acoustic startle reflex. Since sensory filtering is usually already reduced in patients with schizophrenia, the current results call for caution in the widespread use of dual-acting antidepressants in the treatment of depressed or negative symptoms in these patients.