Leveraging Neuroplasticity to Enhance Adaptive Learning: The Potential for Synergistic Somatic-Behavioral Treatment Combinations to Improve Clinical Outcomes in Depression

Abstract

Until recently, therapeutic development in psychiatry was targeted solely toward symptom reduction. While this is a worthwhile goal, it has yielded little progress in improved therapeutics in the last several decades in the field of mood disorders. Recent advancements in our understanding of pathophysiology suggests that an impairment of neuroplasticity may be a critical part of the development of neuropsychiatric disorders. Interventions that enhance or modulate neuroplasticity often reduce depressive symptoms when applied as stand-alone treatments. Unfortunately, when treatments are discontinued, the disease state often returns as patients relapse. However, treatments that enhance or modulate plasticity not only reduce symptom burden, but also may provide an opportune window wherein cognitive or behavioral interventions could be introduced to harness a state of enhanced neuroplasticity and lead to improved longer-term clinical outcomes. Here, we review the potential of synergistically combining plasticity-enhancing and behavioral therapies to develop novel translational treatment approaches for depression. After reviewing relevant neuroplasticity deficits in depression, we survey biological treatments that appear to reverse such deficits in humans, including N-methyl-D-aspartate receptor modulators (ketamine, Dcycloserine), electroconvulsive therapy, and transcranial brain stimulation. We then review

Ketamine Plus Motivational Enhancement Therapy: Leveraging a Rapid Effect to Promote Enduring Change

“…This hypothesis is consistent with broader calls to develop novel interventions that rationally wed the acute, rapid impact of pharmacological or somatic (e.g., neuromodulatory) interventions with behavioral procedures, based on posited complimentary mechanisms (12). Preliminary evidence suggests that ketamine infusion followed immediately by behavioral intervention could potentially produce enduring benefit across a range of disorders (e.g., depression [13], PTSD [14], obsessivecompulsive disorder [15], cocaine dependence [6], and now alcohol dependence).…”

“…Within this approach, rapid-acting pharmacology represents merely the first step in a novel treatment algorithm designed to foster relief that is both rapid and durable, by leveraging learning-based mechanisms. To date, these studies have used small samples and have routinely lacked crucial experimental controls (e.g., each intervention component in the absence of the other) (12). This methodological limitation is applicable to the study by Dakwar and colleagues, in which participants in both arms received motivational enhancement therapy, precluding the ability to distinguish a stand-alone effect of ketamine from a truly synergistic biological-behavioral effect.…”

Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies

“…At the phenomenological level, circadian rhythm disruption and emotion/cognition (E/C) imbalance may be somehow related to the clinical presentation of BD and become targets of psychosocial treatments. A combination of CBT with neurofeedback, or a combination of psychosocial treatment and pharmacotherapy targeting neuroplasticity would enhance the efficacy of these treatments synergistically . The role for photoperiodicity and melatonin in BD is still understudied.…”

“…A combination of CBT with neurofeedback, or a combination of psychosocial treatment and pharmacotherapy targeting neuroplasticity would enhance the efficacy of these treatments synergistically. 270 The role for photoperiodicity and melatonin in BD is still understudied.…”

Psilocybin-assisted therapy for depression: How do we advance the field?

“…This state may offer an invaluable opportunity for psychotherapy to guide and solidify these changes. This concept of pharmacotherapy and psychotherapy working synergistically is gaining traction within psychiatry (see Wilkinson et al, 2018) and the properties of psilocybin may place it at the forefront of this. However, whether there are synergistic or simply additive effects of psilocybin and therapy is yet to be tested.…”