- Valium much less sedating than its predecessors Miltown or Librium (Before Valium came along, millions of Americans begged their doctors for Miltown prescriptions. By 1957, a prescription for Miltown was filled an average of every second in the U.S. Suburbs became the site for Miltown parties, cocktails were named for the pill – a Miltown replaced the olive in a Miltini – and high-end jewelers designed rings with compartments to hold the “tranks.” In 1960, Swiss drug maker Hoffmann-La Roche unveiled Librium, less sedating than Miltown but just as calming. In one famous experiment, the bitter-tasting drug tamed lions and tigers at the San Diego Zoo.)
- By the end of the 1960s, Valium was the top-selling psychotropic drug in the United States
- Valium quickly surpassed Miltown and Librium
- Among Valium’s biggest selling points: no bitter taste, and it was nearly impossible to overdose on (In one widely reported instance that came much later, a Reagan administration official tried to kill himself with a heavy dose of Valium but failed.)
- In the 1970s, Valium became the most widely prescribed drug of any kind
- Valium was everywhere: Mike Brady popped a couple on the television show “The Brady Bunch,” and the Rolling Stones composed an ode to the drug, dubbing it “Mother’s Little Helper”
- Ten of millions of people with anxiety disorders have been able to lead normal lives due to Valium
- Dr. Leo Sternbach a medical hero who deserves posthumous Nobel Prize in Medicine
Diazepam /daɪˈæzɨpæm/, first marketed as Valium /ˈvæliəm/ by Hoffmann-La Roche, is a benzodiazepine drug.
It is commonly used to treat anxiety, panic attacks, insomnia, seizures (including status epilepticus), muscle spasms (such as in tetanus cases), restless legs syndrome, alcohol withdrawal, benzodiazepine withdrawal, opiate withdrawal syndrome and Ménière’s disease. It may also be used before certain medical procedures (such as endoscopies) to reduce tension and anxiety, and in some surgical procedures to induce amnesia.
It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties. The pharmacological action of diazepam enhances the effect of the neurotransmitter GABA by binding to the benzodiazepine site on the GABAA receptor (via the constituent chlorine atom) leading to central nervous system depression.
Adverse effects of diazepam include anterograde amnesia (especially at higher doses) and sedation, as well as paradoxical effects such as excitement, rage or worsening of seizures in epileptics. Benzodiazepines also can cause or worsen depression. Long-term effects of benzodiazepines such as diazepam include tolerance, benzodiazepine dependence and benzodiazepine withdrawal syndrome upon dose reduction. After cessation of benzodiazepines, cognitive deficits may persist for at least six months and it was suggested that longer than six months may be needed for recovery from some deficits. Diazepam also has physical dependence potential and can cause serious problems of physical dependence with long term use. Compared to other benzodiazepines, though, physical withdrawal from diazepam following long term use is usually far more mild due to its long elimination half-life. Diazepam is the drug of choice for treating benzodiazepine dependence, with its low potency, long duration of action and the availability of low-dose tablets making it ideal for gradual dose reduction and the circumvention of withdrawal symptoms.
Advantages of diazepam are a rapid onset of action and high efficacy rates, which is important for managing acute seizures, anxiety attacks and panic attacks; benzodiazepines also have a relatively low toxicity in overdose. Diazepam is a core medicine in the World Health Organization’s Essential Drugs List, which list minimum medical needs for a basic health care system. Diazepam, first synthesized by Leo Sternbach, is used to treat a wide range of conditions, and has been one of the most frequently prescribed medications in the world since its launch in 1963.
Diazepam is mainly used to treat anxiety, insomnia, and symptoms of acute alcohol withdrawal. It is also used as a premedication for inducing sedation, anxiolysis or amnesia before certain medical procedures (e.g., endoscopy).
Intravenous diazepam or lorazepam are first line treatments for status epilepticus; However, lorazepam has advantages over diazepam, including a higher rate of terminating seizures and a more prolonged anticonvulsant effect. Diazepam is rarely used for the long-term treatment of epilepsy because tolerance to its anticonvulsant effects usually develops within six to 12 months of treatment, effectively rendering it useless for that purpose. Diazepam is used for the emergency treatment of eclampsia, when IV magnesium sulfate and blood pressure control measures have failed. Benzodiazepines do not have any pain-relieving properties themselves, and are generally recommended to avoid in individuals with pain. However, benzodiazepines such as diazepam can be used for their muscle-relaxant properties to alleviate pain caused by muscle spasms and various dystonias, including blepharospasm. Tolerance often develops to the muscle relaxant effects of benzodiazepines such as diazepam. Baclofen or tizanidine is sometimes used as an alternative to diazepam.
The anticonvulsant effects of diazepam can help in the treatment of seizures due to a drug overdose or chemical toxicity as a result of exposure to sarin, VX, soman (or other organophosphate poisons; See #CANA), lindane, chloroquine, physostigmine, or pyrethroids Diazepam is sometimes used intermittently for the prophylaxis of febrile seizures caused by high fever in children and neonates under five years of age. Long-term use of diazepam for the management of epilepsy is not recommended; however, a subgroup individuals with treatment resistant epilepsy benefit from long-term benzodiazepines and for such individuals clorazepate has been recommended due to its slower onset of tolerance to the anticonvulsant effects.
Diazepam has a broad spectrum of indications (most of which are off-label), including:
- Treatment of neurovegetative symptoms associated with vertigo
- Treatment of the symptoms of alcohol, opiate and benzodiazepine withdrawal
- Short-term treatment of insomnia
- Treatment of tetanus, together with other measures of intensive treatment
- Adjunctive treatment of spastic muscular paresis (paraplegia/tetraplegia) caused by cerebral or spinal cord conditions such as stroke, multiple sclerosis, or spinal cord injury (long-term treatment is coupled with other rehabilitative measures)
- Palliative treatment of stiff person syndrome
- Pre- or postoperative sedation, anxiolysis and/or amnesia (e.g., before endoscopic or surgical procedures)
- Treatment of complications with a hallucinogen crisis and stimulant overdoses and psychosis, such as LSD, cocaine, or methamphetamine.
- Prophylactic treatment of oxygen toxicity during hyperbaric oxygen therapy
Dosages should be determined on an individual basis, depending upon the condition being treated, severity of symptoms, patient body weight, and any comorbid conditions the patient may have.
Diazepam is marketed in over 500 brands throughout the world. It is supplied in oral, injectable, inhalation and rectal forms.
The United States military employs a specialized diazepam preparation known as CANA (Convulsive Antidote, Nerve Agent), which contains diazepam. One CANA kit is typically issued to service members, along with three Mark I NAAK kits, when operating in circumstances where chemical weapons in the form of nerve agents are considered a potential hazard. Both of these kits deliver drugs using autoinjectors. They are intended for use in “buddy aid” or “self aid” administration of the drugs in the field prior to decontamination and delivery of the patient to definitive medical care.
Diazepam was the second benzodiazepine invented by Dr. Leo Sternbach of Hoffmann-La Roche at the company’s Nutley, New Jersey, facility following chlordiazepoxide (Librium), which was approved for use in 1960. Released in 1963 as an improved version of Librium, diazepam became incredibly popular, helping Roche to become a pharmaceutical industry giant. It is 2.5 times more potent than its predecessor, which it quickly surpassed in terms of sales. After this initial success, other pharmaceutical companies began to introduce other benzodiazepine derivatives.
The benzodiazepines gained popularity among medical professionals as an improvement upon barbiturates, which have a comparatively narrow therapeutic index, and are far more sedating at therapeutic doses. The benzodiazepines are also far less dangerous; death rarely results from diazepam overdose, except in cases where it is consumed with large amounts of other depressants (such as alcohol or other sedatives). Benzodiazepine drugs such as diazepam initially had widespread public support, but with time the view changed to one of growing criticism and calls for restrictions on their prescription.
Diazepam was the top-selling pharmaceutical in the United States from 1969 to 1982, with peak sales in 1978 2.3 billion tablets. Diazepam, along with oxazepam, nitrazepam and temazepam, represents 82% of the benzodiazepine market in Australia. While psychiatrists continue to prescribe diazepam for the short-term relief of anxiety, neurology has taken the lead in prescribing diazepam for the palliative treatment of certain types of epilepsy and spastic activity, for example, forms of paresis. It is also the first line of defense for a rare disorder called stiff-person syndrome. In recent years, the public perception of benzodiazepines has become increasingly negative.
Diazepam is a drug of potential abuse and can cause serious problems of addiction and as a result is scheduled. Urgent action by national governments has been recommended to improve prescribing patterns of benzodiazepines such as diazepam. A single dose of diazepam modulates the dopamine system in similar ways to how morphine and alcohol modulate the dopaminergic pathways. Between 50 and 64% of rats will self administer diazepam. Benzodiazepines including diazepam in animal studies have been shown to increase reward-seeking behaviours by increasing impulsivity, which may suggest an increased risk of addictive behavioural patterns with usage of diazepam or other benzodiazepines. In addition, diazepam has been shown to be able to substitute for the behavioural effects of barbiturates in a primate study. Diazepam has been found as an adulterant in heroin.
Diazepam drug misuse can occur either through recreational misuse where the drug is taken to achieve a high or when the drug is continued long term against medical advice.
Sometimes, it is used by stimulant users to “come down” and sleep and to help control the urge to binge.
A large-scale, nationwide study conducted by SAMHSA found benzodiazepines in the USA are the most frequently abused pharmaceutical, with 35% of drug-related visits to the emergency department involving benzodiazepines.
They are more commonly abused than opiate pharmaceuticals, which accounted for 32% of visits to the emergency department. Males abuse benzodiazepines as commonly as females. Of drugs used in attempted suicide, benzodiazepines are the most commonly used pharmaceutical drug, with 26% of attempted suicides involving benzodiazepines. The most commonly abused benzodiazepine is, however, alprazolam. Clonazepam is the second-most-abused benzodiazepine. Lorazepam is the third-most-abused benzodiazepine, and diazepam the fourth-most-abused benzodiazepine in the USA.
Benzodiazepines, including diazepam, nitrazepam, and flunitrazepam, account for the largest volume of forged drug prescriptions in Sweden, a total of 52% of drug forgeries being for benzodiazepines.
Diazepam was detected in 26% of cases of people suspected of driving under the influence of drugs in Sweden, and its active metabolite nordazepam was detected in 28% of cases. Other benzodiazepines and zolpidem and zopiclone also were found in high numbers. Many drivers had blood levels far exceeding the therapeutic dose range, suggesting a high degree of abuse potential for benzodiazepines and zolpidem and zopiclone. In Northern Ireland in cases where drugs were detected in samples from impaired drivers who were not impaired by alcohol, benzodiazepines were found in 87% of cases. Diazepam was the most commonly detected benzodiazepine.
Diazepam is regulated in most countries as a prescription drug:
- International: diazepam is a Schedule IV controlled drug under the Convention on Psychotropic Substances
- UK: classified as a controlled drug, listed under Schedule IV, Part I (CD Benz POM) of the Misuse of Drugs Regulations 2001, allowing possession with a valid prescription. The Misuse of Drugs Act 1971 makes it illegal to possess the drug without a prescription, and for such purposes it is classified as a Class C drug. “List of Controlled Drugs”
- Germany: classified as a prescription drug, or in high dosage as a restricted drug (Betäubungsmittelgesetz, Anhang III)
The State of California offers diazepam to condemned inmates as a pre-execution sedative as part of their lethal injection program.
Diazepam is used as a short-term sedative and anxiolytic for cats and dogs, sometimes used as an appetite stimulant. It can also be used to stop seizures in dogs and cats.
Valium Saved My Life
Published: October 5, 2012
To the Editor:
Re “Valium’s Contribution to Our New Normal,” by Robin Marantz Henig (Sunday Review, Sept. 30):
After serving in the Army in Vietnam and suffering from what is now called post-traumatic stress disorder, I found that Librium, and then Valium, definitely saved my life.
Whatever negatives there may be about the use and overuse of Valium, it has saved many lives and improved the quality of millions of lives.
Its positives dramatically outweigh its negatives, and right now, there is really no adequate substitute for the psychoactive drugs.
MICHAEL J. GORMAN
Whitestone, Queens, Sept. 30, 2012