Electroencephalogram-based pharmacodynamic measures: a review

Abstract

Pharmacokinetics and pharmacodynamics can provide a useful modeling framework for predicting drug activity and can serve as a basis for dose optimization. Determining a suitable biomarker or surrogate measure of drug effect for pharmacodynamic models can be challenging. The electroencephalograph is a widely-available and non-invasive tool for recording brain-wave activity simultaneously from multiple brain regions. Certain drug classes (such as drugs that act on the central nervous system) also generate a reproducible electroencephalogram (EEG) effect. Characterization of such a drug-induced EEG effect can produce pharmacokinetic/pharmacodynamic models useful for titrating drug levels and expediting development of chemically-similar drug analogs. This paper reviews the relevant concepts involved in pharmacokinetic/pharmacodynamic modeling using EEG-based pharmacodynamic measures. In addition, examples of such models for various drugs are organized by drug activity as well as chemical structure and presented.

Increased power of resting-state gamma oscillations in autism spectrum disorder detected by routine electroencephalography

“…However, after exclusion of ASD patients with an intellectual disability, differences in gamma power remained significant. Further, medication use in the patient group could be accountable for altered spectral power in different frequency bands [15]. Again, after excluding ASD patients on medication, similar results were obtained.…”

EEG Source Reconstruction in Male Nonsmokers after Nicotine Administration during the Resting State

“…Therefore, individual pharmacokinetic variability is still an issue. Bewernitz and Derendorf [57] showed how pharmacokinetics could inform pharmacodynamics (i.e. drug-induced brain activity).…”

Translational psychiatry—light at the end of the tunnel

“…On the basis of our experience from the application of qEEG to multiple CNS discovery programs as well as selected examples from the published literature, we will discuss several key factors that impact translatability. Many articles and reviews have been published on qEEG as a potential pharmacodynamic measure for early discovery . Some have focused on analytical methods for qEEG that need to be appreciated for effective application .…”

“…A recent study used two NMDA channel blockers, ketamine and lanicemine, to show robust and dose‐dependent increases in gamma oscillations in rodents that were subsequently translated into healthy human volunteers . In addition to these two examples, there is a significant body of literature that suggests that this translational approach is indeed viable for certain classes of drugs …”