#394 ‒ Sleep pharmacology: the role of medications in healthy sleep, the promise of emerging therapies, and the evidence for common sleep supplements

Sleep pharmacology requires precise matching of interventions to the four primary drivers of sleep dysfunction: homeostatic pressure, circadian timing, hyperarousal, and sleep architecture. While behavioral strategies like cognitive behavioral therapy for insomnia (CBTI) remain the first-line foundation, pharmacological agents serve as targeted tools for specific imbalances. Dual Orexin Receptor Antagonists (DORAs) offer a superior profile by reducing wakefulness signals without forcing sedation, potentially supporting glymphatic waste clearance linked to long-term neurological health. Conversely, benzodiazepines and Z-drugs often disrupt natural sleep architecture and carry significant risks of dependence and cognitive impairment. Melatonin and its receptor agonists function primarily as circadian regulators rather than sedatives, making them effective for timing-related issues like jet lag. Effective clinical management demands identifying the underlying mechanism to avoid the common pitfalls of tolerance, dependence, and fragmented, non-restorative sleep.