Temazepam


Temazepam, sold under the brand name Restoril among others, is a medication of the benzodiazepine class which is generally used to treat severe or debilitating insomnia. It is taken by mouth. Temazepam is rapidly absorbed, and significant hypnotic and anxiolytic effects begin in less than 30 minutes and can last for up to eight hours. Prescriptions for hypnotics, such as temazepam, have seen a dramatic decrease since 2010, while anxiolytics, such as alprazolam, clonazepam, and lorazepam, have increased or remained stable. Temazepam and similar hypnotics, such as triazolam, are generally reserved for severe and debilitating insomnia. They have largely been replaced by z-drugs and atypical antidepressants as first line treatment for insomnia.
Common side effects include drowsiness, motor and cognitive impairment, lethargy, confusion, euphoria, and dizziness. Serious side effects may include hallucinations, hypotension, respiratory depression, abuse, anaphylaxis, and suicide. Use is generally not recommended together with alcohol or opioids. If the dose is rapidly decreased withdrawal may occur. Use during pregnancy or breastfeeding is not recommended. Temazepam is a short-acting benzodiazepine and hypnotic. It works by affecting GABA within the brain.
Temazepam was patented in 1962 and came into medical use in 1969. It is available as a generic medication. In 2021, it was the 208th most commonly prescribed medication in the United States, with more than 2million prescriptions.

Medical uses

In sleep laboratory studies, temazepam significantly decreased the number of nightly awakenings, but has the drawback of distorting the normal sleep pattern. It is officially indicated for severe insomnia and other severe or disabling sleep disorders. The prescribing guidelines in the UK advise the prescribing of hypnotics to two to four weeks and longer to be avoided, due to concerns of tolerance and dependence.
The American Academy of Sleep Medicine's 2017 clinical practice guidelines recommended the use of temazepam in the treatment of sleep-onset and sleep-maintenance insomnia. It rated the recommendation as weak, the quality of evidence as moderate, and concluded that the potential benefits outweighed the potential harms. The guidelines found that temazepam at a dose of 15mg reduces sleep latency by 37minutes, increases total sleep time by 99minutes, and provides a small improvement to sleep quality. The improvements in sleep latency and total sleep time were numerically much greater than any of the other included sleep medications, including eszopiclone, zopiclone, zolpidem, triazolam, estazolam, quazepam, flurazepam, trazodone, diphenhydramine, gabapentin, among others.
The United States Air Force uses temazepam as one of the hypnotics approved as a "no-go pill" to help aviators and special-duty personnel sleep in support of mission readiness. "Ground tests" are necessary prior to required authorization being issued to use the medication in an operational situation, and a 12-hour restriction is imposed on subsequent flight operation. The other hypnotics used as "no-go pills" are zaleplon and zolpidem, which have shorter mandatory recovery periods.

Contraindications

Use of temazepam should be avoided, when possible, in individuals with these conditions:
The safety and effectiveness of temazepam has not been established in children. Benzodiazepines also require special caution if used in the elderly, alcohol- or drug-dependent individuals, and individuals with comorbid psychiatric disorders.
Temazepam, similar to other benzodiazepines and nonbenzodiazepine hypnotic drugs, causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. Falls and hip fractures are frequently reported. The combination with alcohol increases these impairments. Partial but incomplete tolerance develops to these impairments. The smallest possible effective dose should be used in elderly or very ill patients, as a risk of apnea and/or cardiac arrest exists. This risk is increased when temazepam is given concomitantly with other drugs that depress the central nervous system.

Misuse and dependence

Because benzodiazepines can be abused and lead to dependence, their use should be avoided in people in certain particularly high-risk groups. These groups include people with a history of alcohol or drug dependence, people significantly struggling with their mood or people with longstanding mental health difficulties. If temazepam must be prescribed to people in these groups, they should generally be monitored very closely for signs of misuse and development of dependence.

Adverse effects

In September 2020, the U.S. Food and Drug Administration required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.

Common

Side effects are typical of hypnotic benzodiazepines, though temazepam has more pronounced CNS depressant effects, and include somnolence, sedation, dizziness, fatigue, ataxia, headache, lethargy, impairment of memory and learning, longer reaction time and impairment of motor functions, slurred speech, decreased physical performance, numbed emotions, reduced alertness, muscle weakness, blurred vision, and inattention. Euphoria was a reported side effect with its use, which is uncommon or not ever reported amongst benzodiazepines. According to the U.S. Food and Drug Administration, temazepam had an incidence of euphoria of 1.5%, which is considered rare. Feelings of euphoria, pleasant sedation, and inner feelings of peace are reported by those who abuse drugs, particularly in those who use temazepam intravenously. It has the highest ratings reported among benzodiazepines by recreational drug users. Drug users tend have a higher preference for temazepam over other benzodiazepines. The three most common reasons for temazepam preference were due to speed of onset, that a it was 'strong' and that it gave a good 'high'. Anterograde amnesia is also common, and respiratory depression in higher doses has proven to be fatal, even when temazepam is taken alone. In medical literature from Australia, Ireland, the UK, Canada, and the United States, temazepam is the only benzodiazepine which has been fatal in overdoses without combination with other CNS depresssants. This unique feature is due to the toxicity of the drug, which numerous studies have ranked it as being most toxic.
A 2009 meta-analysis found a 44% higher rate of mild infections, such as pharyngitis or sinusitis, in people taking Temazepam or other hypnotic drugs compared to those taking a placebo.

Less common

, hypotension, burning eyes, increased appetite, changes in libido, hallucinations, faintness, nystagmus, vomiting, pruritus, gastrointestinal disturbances, nightmares, palpitation and paradoxical reactions including restlessness, aggression, violence, overstimulation and agitation have been reported, but are rare.
Before taking temazepam, one should ensure that at least 8 hours are available to dedicate to sleep. Failing to do so can increase the side effects of the drug.
Like all benzodiazepines, the use of this drug in combination with alcohol potentiates the side effects, and can lead to toxicity and death.
Though rare, residual "hangover" effects after night-time administration of temazepam occasionally occur. These include sleepiness, impaired psychomotor and cognitive functions which may persist into the next day, impaired driving ability, and possible increased risks of falls and hip fractures, especially in the elderly.

Tolerance

Chronic or excessive use of temazepam may cause drug tolerance, which can develop rapidly, so this drug is not recommended for long-term use. In 1979, the Institute of Medicine and the National Institute on Drug Abuse stated that most hypnotics lose their sleep-inducing properties after about three to 14 days. In use longer than one to two weeks, tolerance will rapidly develop towards the ability of temazepam to maintain sleep, resulting in a loss of effectiveness. Some studies have observed tolerance to temazepam after as little as one week's use. Another study examined the short-term effects of the accumulation of temazepam over seven days in elderly inpatients, and found little tolerance developed during the accumulation of the drug. Other studies examined the use of temazepam over six days and saw no evidence of tolerance. A study in 11 young male subjects showed significant tolerance occurs to temazepam's thermoregulatory effects and sleep inducing properties after one week of use of 30-mg temazepam. Body temperature is well correlated with the sleep-inducing or insomnia-promoting properties of drugs.
In one study, the drug sensitivity of people who had used temazepam for one to 20 years was no different from that of controls. An additional study, in which at least one of the authors is employed by multiple drug companies, examined the efficacy of temazepam treatment on chronic insomnia over three months, and saw no drug tolerance, with the authors even suggesting the drug might become more effective over time.
Establishing continued efficacy beyond a few weeks can be complicated by the difficulty in distinguishing between the return of the original insomnia complaint and withdrawal or rebound related insomnia. Sleep EEG studies on hypnotic benzodiazepines show tolerance tends to occur completely after one to four weeks with sleep EEG returning to pretreatment levels. The paper concluded that due to concerns about long-term use involving toxicity, tolerance and dependence, as well as to controversy over long-term efficacy, wise prescribers should restrict benzodiazepines to a few weeks and avoid continuing prescriptions for months or years. A review of the literature found the nonpharmacological treatment options were a more effective treatment option for insomnia due to their sustained improvements in sleep quality.