Toward specific ways to combine ketamine and psychotherapy in treating depression

Around 50% of people with major depression respond to monoaminergic antidepressants, which modulate synapses but do not substantially influence synaptogenesis. They also increase brain-derived neurotrophic factor (BDNF), but for activity-dependent plasticity, BDNF release must work with synaptogenesis. Ketamine, in contrast, leads to fast changes in synaptic function and plasticity beyond classical antidepressants, suggesting it could enhance psychotherapy effects. Since ketamine's purely pharmacological effect is transient, such enhancement may become an important clinical indication. The editorial outlines mechanistic hypotheses for how Behavioral Activation, Trauma-Focused Psychotherapies, and Humanistic Psychotherapy may prolong ketamine's antidepressant effects.

Study at a glance

Abstract

In major depression, remission rate in response to monoaminergic antidepressant is around 50%. The lack of strong synergies between classical antidepressants and psychotherapy may be due to the molecular effects of classical antidepressants. They modulate synapses but they do not substantially influence synaptogenesis. They also increase brain-derived neurotrophic factor (BDNF). However, for activity-dependent plasticity, BDNF release has to work in concert with activation of synaptogenesis. There has been considerable excitement about ketamine’s antidepressant effect. Ketamine leads to fast changes in synaptic function and plasticity that go well beyond effects of classical antidepressants. As a result, ketamine may turn out to have the capacity to considerably enhance the effects of psychotherapy. Such enhancing effects may become an important clinical indication for ketamine since its purely pharmacological effect is transient. This editorial outlines some mechanistic hypotheses, how Behavioral Activation, Trauma-Focused Psychotherapies and Humanistic Psychotherapy may specifically prolong ketamine’s antidepressant effects.