Dose selection and trial results

Ever heard of neurasthenia, aka Americanitis? It was the first epidemic of the 20th century - and it's number one symptom was insomnia.

It may have just been the electricity.

In this episode of Drug Story, we step into that sweet oblivion called sleep, and that infernal torment called insomnia. We visit hustle culture, where sleep is just an obstacle to crushing it.

And we learn about Ambien: the most popular sleeping pill ever invented. Until women started showing up in emergency rooms with amnesia...

Sources for this episode

[1] NEURASTHENIA, DEGENERACY, AND MOBILE ORGANS (1906) The British Medical Journal: Neurasthenia is defined by a state of "nervous exhaustion" and can include physical symptoms like head or spinal pain, insomnia, and constipation, along with mental depression.

[2] Neurasthenia and a Modernizing America (2003) JAMA: Introduces neurasthenia after the Civil War as a nervous-energy disorder; the term declined in use after the 1930s.

[3] ‘Americanitis’: The Disease of Living Too Fast (2016) The Atlantic: Frames neurasthenia as a disease of living too fast in industrializing America.

[4] Insomnia and the late nineteenth-century insomniac: the case of Albert Kimball (2020) Interface Focus:The identity of the “insomniac” emerged alongside industrial-era stress and the concept of neurasthenia.

[5] A short history of insomnia and how we became obsessed with sleep (2023) The Conversation: Industrialization increased insomnia rates through artificial lighting, work shifts, and societal change.

[6] The Pathophysiology of Insomnia (2015) Contemporary Reviews In Sleep Medicine: Insomnia can be influenced by genetics, cellular and physiological mechanisms, and sleep behaviors.

[7] Insomnia: a cultural history (2018) The Lancet: Contrasts pre-industrial ritualized sleep with modern increases in chronic insomnia.

[8] Phenome-wide Analysis of Diseases in Relation to Objectively Measured Sleep Traits and Comparison with Subjective Sleep Traits in 88,461 Adults (2025) Health Data Science: In a research study, poor sleep quality was associated with increased risk for 172 different diseases including Parkinson's disease and type 2 diabetes.

[9] A Short History of Sleeping Pills (2018) Sleep Review: The history of treatments for insomnia covering alcohol, opiates, barbiturates, benzodiazepines, and “Z drugs” like Ambien.

[10] The Evolution and Development of Insomnia Pharmacotherapies (2007) Journal of Clinical Sleep Medicine: History of pharmacological treatment for insomnia: from older, less safe options like barbiturates to the current generation of medications with improved safety profile.

[11] The Big Sleep (2013) The New Yorker: In 1973, Jean-Pierre Kaplan began work on a new class of sleeping pills at Synthélabo, leading to zolpidem’s development.

[12] Critics say drug ads should be a wake-up call (2006) Star News: Critics link increased use of Ambien and Lunesta to aggressive advertising campaigns.

[13] Evaluation of the long term efficacy and safety of zolpidem-MR 12.5 mg compared to placebo, when both are administered over a long term period “as needed”, in patients with chronic primary insomnia (2008) Sanofi-Aventis: Summary of Phase III clinical trial investigating the long-term efficacy and safety of the extended-release sleep medication, zolpidem.

[14] Emergency Department Visits for Adverse Reactions Involving the Insomnia Medication Zolpidem (2013) SAMHSA: There was a 220% increase in emergency department visits related to adverse reactions from the sleep medication zolpidem between 2005 and 2010

[15] FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR (2013) The U.S. Food and Drug Administration: FDA recommended lower doses and advised avoiding driving the day after using Ambien CR.

[16] FDA adds Boxed Warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines (2019) The U.S. Food and Drug Administration: The official safety communication from the FDA announcing a Boxed Warning for specific prescription insomnia medications, including eszopiclone, zaleplon, and zolpidem, due to reports of dangerous side effects.

[17] Zolpidem-Induced Sleepwalking, Sleep Related Eating Disorder, and Sleep-Driving: Fluorine-18-Flourodeoxyglucose Positron Emission Tomography Analysis, and a Literature Review of Other Unexpected Clinical Effects of Zolpidem (2009) Journal of Clinical Sleep Medicine: PET scans and literature review on zolpidem’s association with abnormal sleep behaviors.

[18] Zolpidem and Driving Impairment — Identifying Persons at Risk (2013) New England Journal of Medicine: Examines risks of zolpidem, including sleepwalking, sleep-related eating disorder, and sleep-driving.