Better Biomarkers, Faster Drugs, Stronger Models: Progress Towards Precision Psychiatry.
Missouri medicine – January 01, 2023
Source: PubMed
Summary
Anhedonia, once just a symptom of depression, is now recognized as a key target for treatment, reflecting a shift toward precision psychiatry. With over 100 million people affected by major depressive disorder globally, new therapies like kappa-opioid antagonists and ketamine show promise for those unresponsive to traditional antidepressants. Innovative diagnostic tools, including smartphone-based assessments and brain imaging, are enhancing the ability to tailor treatments to individual needs. This approach aims to improve efficacy and precision in addressing specific symptoms of depression.
Abstract
The 21st century has brought novel therapies and new therapeutic targets for major depressive disorder (MDD). Until recently all antidepressant medications targeted monoamines-serotonin, norepinephrine, and dopamine- and their regulatory systems. But growing evidence has suggested that individuals who fail to respond to a monoaminergic treatment are likely to fail to respond to other monoaminergic options. The emergence in recent years of treatment targets beyond the monoaminergic systems (e.g. κ-opioid antagonists, ketamine and other NMDA modulators, neurosteroids) has cultivated hopes for not only greater efficacy in treating depression, but also improved precision in targeting specific phenotypes and symptoms. Concurrently, an expanding repertoire of diagnostic and assessment tools-such as smartphone-based experience sampling and brain imaging-is moving the field toward more reliable and symptom-specific measurement with greater descriptive and prescriptive power. Taken together, these diagnostic tools and treatment options herald a new era of "precision psychiatry"-the selection and implementation of an optimal treatment for an individual patient's particular needs. Anhedonia offers an example of the new precision psychiatry. Anhedonia has moved from merely one among several criteria for depression to a transdiagnostic psychopathology which can be understood neurobiologically, assessed quantitatively, and centered as a primary target in research and development of novel pharmacotherapies. We describe functional testing of reward circuits in the development of kappa-opioid antagonists for anhedonia. This offers a lens for understanding how and under what circumstances other novel treatments, such as psychedelics, might find a place in the future landscape of precision psychiatric care.