The Matt Walker Podcast

#93 - Sleeping Pills and their Alternatives with Dr. Ranji Varghese

Mar 3, 2025

Dr. Ranji Varghese, an expert in sleep medicine, returns to discuss the nuances of sleeping pills. He highlights the effectiveness and mechanisms of newer alternatives like melatonin receptor agonists and DORAs, contrasting them with traditional options. The chat covers side effects, the importance of cautious use, and the role of CBTI in treating chronic insomnia. Dr. Varghese emphasizes that sleeping pills should be seen as tools rather than cures, advocating for open communication with doctors to tailor treatment safely.

01:00:13

Episode guests

Dr. Ranji Varghese

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Episode notes

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Quick takeaways

Melatonin receptor agonists, such as Ramelteon, provide a reliable sleep aid that signals sleep preparation rather than inducing immediate sleepiness.

Dual orexin receptor antagonists (DORAs) offer a novel approach to managing insomnia by inhibiting wakefulness-promoting orexin, but require careful monitoring for side effects.

Deep dives

Understanding Melatonin Receptor Agonists

Melatonin receptor agonists represent a unique class of sleep aids that target specific melatonin receptors in the brain, distinct from traditional sleeping pills that work on GABA receptors. These medications signal to the brain that it's time to prepare for sleep rather than inducing immediate sleepiness like other sedatives. The most notable example, Remelteon, has been found effective for sleep onset insomnia and is well-tolerated by patients. Unlike over-the-counter melatonin supplements, which can vary greatly in purity, prescription melatonin receptor agonists offer a consistent and reliable dosage, reducing the uncertainties associated with self-medication.

Intro

4min

Exploring Melatonin and DORAs for Insomnia

9min

Unpacking Sleep Medications

6min

Exploring DORAs and Off-Label Sleep Medications

9min

Understanding Trazodone: Mechanisms and Side Effects

5min

Navigating Off-Label Sleep Aids

9min

Exploring the Risks and Efficacy of Sleeping Medications

4min

Navigating Sleep Medications: Risks and Alternatives

14min

Matt Walker welcomes Dr. Ranji Varghese back to the podcast today to complete the whole sleeping pill story by discussing newer sleeping pills, beyond benzos and Z-drugs. Together, they explore Melatonin receptor agonists (like Ramelteon) that signal sleep preparation, unlike sedating GABAergics. They also detail how DORAs inhibit the wakefulness-promoting orexin, how off-label options (ex. trazodone, low-dose doxepin) affect histamine, the risks and benefits of each.

Dr. Varghese goes on to explain the mechanisms and side effect profile for each sleeping pill, including over the counter options. He stresses that all medications carry risk and require careful use, noting that sleeping pills are tools not cures, and that CBTI is preferred for chronic insomnia. Our duo finish up by reminding listeners that open communication with your doctor is vital for safe, short-term medication use.

Please note that Matt is not a medical doctor, and none of the content in this podcast should be considered medical advice in any way, shape, or form, nor prescriptive in any way.

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As always, if you have thoughts or feedback you’d like to share, please reach out:

Matt: Instagram @drmattwalker, X @sleepdiplomat,

YouTube https://www.youtube.com/@sleepdiplomatmattwalker9299

Dr. Varghese:

LinkedIn: https://www.linkedin.com/in/ranji-varghese-md-3591665a/

Minnesota Regional Sleep Disorders Center:
https://www.hennepinhealthcare.org/specialty/minnesota-regional-sleep-disorders-center/

Institute for Integrative Therapies: @iit-mn.com