Journal
NEUROPHARMACOLOGY
Volume 226, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2023.109418
Keywords
Evidence-based drug discovery; Anxiolytic pharmacological therapy; Psychedelics; Cognitive enhancers of exposure therapy; RDoC
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Psychiatric disorders associated with trauma, stress, and anxiety are increasing worldwide, leading to significant morbidity. Current medication-based therapeutic approaches for anxiety disorders and PTSD are effective but have unwanted side effects and do not address underlying pathophysiology. There is renewed interest in designing novel drug treatments in this field, targeting various neurochemical systems. This article provides an overview of the current state of drug development, highlighting the importance of neurobiology and neuroplasticity in achieving lasting therapeutic effects.
Psychiatric disorders associated with psychological trauma, stress and anxiety are a highly prevalent and increasing cause of morbidity worldwide. Current therapeutic approaches, including medication, are effective in alleviating symptoms of anxiety disorders and posttraumatic stress disorder (PTSD), at least in some individuals, but have unwanted side-effects and do not resolve underlying pathophysiology. After a period of stagnation, there is renewed enthusiasm from public, academic and commercial parties in designing and developing drug treatments for these disorders. Here, we aim to provide a snapshot of the current state of this field that is written for neuropharmacologists, but also practicing clinicians and the interested lay-reader. After introducing currently available drug treatments, we summarize recent/ongoing clinical assessment of novel medicines for anxiety and PTSD, grouped according to primary neurochemical targets and their potential to produce acute and/or enduring therapeutic effects. The evaluation of putative treatments targeting monoamine (including psychedelics), GABA, glutamate, cannabinoid, cholinergic and neuropeptide systems, amongst others, are discussed. We emphasize the importance of designing and clinically assessing new medications based on a firm understanding of the under-lying neurobiology stemming from the rapid advances being made in neuroscience. This includes harnessing neuroplasticity to bring about lasting beneficial changes in the brain rather than - as many current medications do - produce a transient attenuation of symptoms, as exemplified by combining psychotropic/cognitive enhancing drugs with psychotherapeutic approaches. We conclude by noting some of the other emerging trends in this promising new phase of drug development.
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