Herbie Murray
Sleeping pills, also known as hypnotics, have been used in various forms throughout human history. The modern sleeping pill dates back to the mid-1800s with the discovery of chloral hydrate, which was quickly adopted as a sleeping aid. By the early 1900s, barbiturates emerged as a replacement for chloral hydrate due to their stronger sedative effects and reduced health risks. However, barbiturates had their drawbacks, including addiction, withdrawal, and overdose toxicity. In the 1950s, researchers sought to develop less toxic alternatives, leading to the introduction of benzodiazepines in the 1960s and 1970s. Today, sleeping pills remain widely prescribed, with ongoing research into safer and more effective alternatives.
| Characteristics | Values |
|---|---|
| Date of invention | The modern sleeping pill dates back to the mid-1800s |
| First sleeping pill invented | Chloral hydrate |
| Date of first invention | 1869 |
| Other early sleeping pills | Barbiturates, opium, cannabis, valerian, ancient herbal remedies, paraldehyde, bromide salts, quinazolinones, benzodiazepines |
| Date of barbiturates invention | 1904 |
| Date benzodiazepines were introduced | 1970s |
| Number of benzodiazepines marketed worldwide | 30 |
| First benzodiazepine marketed for sleep | Flurazepam |
| Year Flurazepam became most widely-prescribed sleeping pill | 1972 |
| Number of Americans with a prescription for sleeping medication | 4% |
| Number of prescriptions for Zolpidem | 9 million |
| Number of people hospitalised from Zolpidem in 2010 | 64,000 |
| Percentage of people with sleep disorders taking nonbenzodiazepines | 13.7% |
| Percentage of people with sleep disorders taking benzodiazepines | 10.8% |
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What You'll Learn
The 19th century: Alcohol, opium, and herbal remedies
The history of sleeping pills can be traced back to the 19th century, when alcohol, opium, and herbal remedies were commonly used to induce sleep. While these substances have a long history of use, they were not without their drawbacks and side effects.
Alcohol, for example, can help people fall asleep faster, but it is quickly metabolized by the body. This leads to a "mini-withdrawal" effect during the second half of the night, resulting in interrupted sleep and a feeling of unrefreshing sleep upon awakening. Long-term alcohol abuse can also lead to chronic sleep disturbances, with individuals often drinking in the hopes of improving their sleep.
Opium and its derivatives, such as morphine and heroin, were also used in the 19th century for their sedative effects. While they could induce sleep, they also had negative consequences. Advertisements from the 1800s claimed that opium products could "produce sleep and composure, relieve pain and irritation, nervous excitement and morbid irritability of body and mind", but they were also associated with addiction and serious health risks. During the American Civil War, opium and morphine gained popularity as pain management drugs for soldiers, leading to thousands of veterans becoming addicted.
Herbal remedies, such as cannabis, valerian, and other ancient herbal remedies, were also used in the 19th century to promote sleep. However, the effectiveness and safety profiles of these remedies is not well documented.
In the mid-19th century, chloral hydrate was discovered, marking a significant development in the evolution of sleeping pills. While it gained popularity as a sleep aid, it also carried risks of dependence, overdose toxicity, and potential organ damage. This prompted the search for alternative sedatives with improved safety profiles.
The discovery of chloral hydrate and the subsequent exploration of sedative drugs laid the foundation for the development of barbiturates as clinical sedatives in the early 20th century. Barbiturates were initially celebrated as potent inducers of sleep, but they too presented challenges. They were highly toxic in overdose, suppressed respiration, and could lead to tolerance, dependence, and serious withdrawal symptoms.
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1857: Bromides introduced by Sir Charles Locock
The history of sleeping pills can be traced back to the mid-19th century with the discovery of chloral hydrate, a soporific first used in 1869. However, the story of their development is filled with twists and turns, including the introduction of bromides by Sir Charles Locock in 1857.
On 12 May 1857, Edward Sieveking presented a paper on epilepsy to the Royal Medical and Chirurgical Society in London. During the ensuing discussion, Sir Charles Locock, an obstetrician to Queen Victoria, revealed that he had successfully used potassium bromide to treat epileptic seizures in women with 'hysterical' or catamenial epilepsy. Locock's treatment was considered groundbreaking as it reduced seizures and calmed sexual excitement in his patients. This report led to Locock being credited with introducing the first reasonably effective antiepileptic drug into medical practice.
Locock's work with bromides is particularly notable as it represented an early attempt to address sleep disorders and epilepsy using medicinal interventions. At the time, sleep disturbances such as insomnia were primarily recognised through self-awareness or the observation of strange behavioural acts during sleep, like sleepwalking or sleep terrors. Locock's introduction of bromides expanded the understanding and treatment of sleep-related issues, paving the way for further advancements in sleep medicine.
However, it is important to note that the original reports of Locock's comments have been questioned, and others who attempted to replicate his success in treating epilepsy with potassium bromide did not achieve the expected results. Despite this, Locock's contribution remains significant in the historical context of sleep medicine and the development of sleeping pills.
Sir Charles Locock retired from medicine in the same year that he introduced bromides, 1857, and was created a baronet. He pursued a variety of endeavours following his retirement, including politics and involvement with the Royal Society.
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1897: First sleep cure with bromide salts
The history of sleeping pills can be traced back to the mid-19th century with the discovery of chloral hydrate. However, it was not until 1897 that the first sleep cure with bromide salts was introduced by British doctor Neil MacLeod in Shanghai.
Bromides, or bromine, have been traditionally used to aid sleep and were the first widely used sedatives in medicine. They were also used in smaller doses for their calming effects and to control anxiety. The use of bromide salts as a cure for sleep was a significant development, as it offered a new approach to treating sleep disorders.
The discovery of the sedative properties of bromide salts can be attributed to Charles Lockock, a London internist, in the mid-1850s. He found that bromide salts had anticonvulsant and sedative effects. However, it was Neil Macleod who, in 1900, reported on "bromide sleep" in the context of treating acute mania.
Bromide salts were not without their drawbacks. They were difficult to use because their activity depended on various factors such as the amount of bromide given, the patient's chloride intake, fluid consumption, and renal function. Additionally, bromide salts had a slow excretion rate and rapid accumulation in the blood, which could lead to bromide intoxication and toxic delirium at high levels.
Despite these challenges, the discovery of bromide salts as a sleep cure paved the way for further advancements in the field of sleep medicine and the development of new generations of sleeping pills with improved safety and efficacy.
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1904: Barbiturates hit the market
The first sleeping pills were invented in the mid-19th century with the discovery of chloral hydrate. However, the first barbiturates, a class of drugs chemically derived from barbituric acid, hit the market in 1904. These were the first widely available sleeping pills.
Barbiturates were developed as sedatives at the beginning of the 20th century by German scientists Emil Fischer and Joseph von Mering, who worked for the company Bayer. They discovered that barbital was very effective in putting dogs to sleep. Fischer and von Mering built on the work of German chemist Adolf von Baeyer, who first synthesised barbituric acid in 1864.
Barbiturates were initially celebrated as potent inducers of sleep. They were used to treat anxiety, insomnia, and seizure disorders. They were also used as anticonvulsants and general anesthetics. However, over time, their many drawbacks became evident. Barbiturates were highly addictive and had a high potential for overdose. They were also known to suppress REM sleep, which became a concern as sleep medicine developed.
By the 1970s, barbiturates had been largely replaced by benzodiazepines, which were perceived as safer alternatives. Benzodiazepines were less toxic in overdose and were not suppressors of REM sleep. However, benzodiazepines also have drawbacks, including the potential for substance dependence and death from overdose, especially when combined with alcohol or other depressants.
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1957: Leo Sternbach's benzodiazepine discovery
The history of sleeping pills began with the discovery of chloral hydrate in the 19th century and the clinical development of barbiturates as sedatives at the beginning of the 20th century. However, barbiturates had many drawbacks, including reduced effectiveness over time and the development of dependence. They were also highly toxic in overdose and could cause fatal respiratory suppression.
In the 1950s, Leo Sternbach, a researcher at the drug company Hoffman-La Roche, sought to find substances with the sedative properties of barbiturates but with less toxicity in overdose. After initial attempts proved unsuccessful, Sternbach abandoned the project. However, in 1957, while cleaning out bottles of old compounds, he discovered a 'nicely crystalline' compound with sedative, anticonvulsant, and muscle relaxant properties. This compound, later identified as the R0 6-690 compound, formed the basis for Librium, the first benzodiazepine tranquilizer to be marketed.
Librium was launched worldwide in 1960 and, by the 1970s, benzodiazepines had become the most widely prescribed drugs globally. Benzodiazepines were perceived as significant improvements over barbiturates and older drugs like glutethimide and methaqualone. They were considered safer and less toxic in overdose, and they had minimal REM sleep reduction. The first benzodiazepine marketed specifically for sleep was flurazepam in 1970, and within two years, it became the most widely prescribed sleeping pill.
Sternbach is credited with the discovery of benzodiazepines, a new class of safe and effective tranquilizers to treat sleep and anxiety disorders. In addition to Librium, he also developed Valium, which, along with Librium, proved to be more effective at reducing stress and anxiety than previous tranquilizers and had fewer side effects. Sternbach's work on benzodiazepines improved many lives and prompted further research and development in this drug class.
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Frequently asked questions
The modern sleeping pill dates back to the mid-1800s with the invention of chloral hydrate.
Chloral hydrate was a drug used to suppress the body and provide an intoxicating effect. It was first used as a soporific in 1869 and quickly became a popular sleeping aid.
Barbiturates replaced chloral hydrate in the early 1900s as they had a stronger sedative effect and were considered less risky.
Barbiturates are a class of drugs with hypnotic and sedative properties. They were first discovered in 1904 and were widely used for sleep disorders, epilepsy, and anesthesia.
In the 1970s, modern drugs like quinazolinones and benzodiazepines were introduced as safer alternatives to barbiturates. Benzodiazepines, in particular, were perceived to have many advantages over barbiturates, including reduced toxicity in overdose and less potential for abuse.
