Ketamine Therapy For Internalizing Disorders: Is There A Single Mechanism?

Internalizing disorders, characterized by quiet, internal distress, include DSM5 diagnoses such as Generalized Anxiety Disorder, Social Anxiety Disorder, Major Depressive Disorder, Panic Disorder, Post-Traumatic Stress Disorder, Obsessive Compulsive Disorder and phobic states.

In contrast to slow and variable responsiveness to conventional medications, ketamine is rapidly effective in all internalizing disorders assessed so far. To account for these differences in speed of onset and breadth of activity between conventional treatments and ketamine, we have recently proposed a ‘double hit’ model for internalizing disorders, with 2 distinct forms of neural dysfunction to coincide. One hit, which is sensitive to ketamine, is disorder general: dysfunction of a neural system linked to high levels of the personality trait of neuroticism. The other hit is disorder-specific: dysfunction of one of a set of disorder-specific neural modules (already identified by theory), each with its own particular pattern of sensitivity to conventional drugs.

We predict that ketamine will produce similar right frontal EEG changes that will correlate with symptom improvement across all of these internalizing disorders. These findings will potentially provide clinicians and researchers with results that could produce major theoretical advances (e.g. for reclassification of anxiety and depressive disorders) and may support wider use of ketamine as a treatment for internalizing disorders.