Tools
Temazepam
Indications
Temazepam, a member of the benzodiazepine class, is identified by its chemical name, 7-chloro-1,3-dihydro-3-hydroxy-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, and is synthesized from the intermediate product of oxazepam.[1][2] Temazepam is classified as a positive allosteric modulator of gamma-aminobutyric acid (GABA-PAM). The pharmacological effects of the drug are attained by modulating GABA, leading to an increase in GABA's inhibitory effects on neuronal excitability.[3]
Temazepam was introduced to the market in 1964. However, it was during the 1980s that the drug experienced a significant surge in popularity, emerging as one of the most frequently prescribed medications for recreational use in various European countries.[4]
Temazepam is known by various street names, including Eggs, Green Eggs, Jellies, Norries, Rugby Balls, Tems, and Mozzies. Temazepam has a high potential risk of abuse, misuse, addiction, physical dependency, and withdrawal responses, consistent with the risk profile associated with all benzodiazepines.[5] The Drug Enforcement Administration (DEA) and the U.S. Food and Drug Administration (FDA) enforce the classification of temazepam as a Schedule IV controlled substance in the United States.[6]
FDA-Approved Indications
Although temazepam was approved for use in the United States in 1981, it remains a popular drug, with over 2 million prescriptions filled annually.[7] Temazepam is indicated for the short-term management of insomnia, with instructions typically recommending its use for 7 to 10 days. The conclusive assessment of sleep latency is conducted after the completion of the treatment regimen.[8]
Temazepam is used to treat insomnia and other sleep-related issues, including frequent awakenings during the night or early in the morning. Research indicates that temazepam is effective in maintaining sleep, although its impact on the delay in sleep onset is relatively modest.[9] Further research indicates that temazepam significantly affects persistent sleep latency within the 15- to 30-mg range, resulting in an average reduction of approximately 25% to 50%. The effects of temazepam on the structure of sleep are minimal, displaying the typical benzodiazepine effect of decreasing stages 3 and 4. However, this outcome has shown inconsistencies and may be sensitive to dosage and duration. Non-rapid eye movement (REM) sleep is typically unaffected.[9][10]
Off-Label Uses
Studies have demonstrated that temazepam can be beneficial in addressing sleep disruptions associated with jet lag. Consideration may also be given to the use of temazepam in short-term shift work and acute stress situations.[11][12][13] Temazepam may also be regarded as a potential remedy for "acute mountain sickness"—a condition often experienced by mountain climbers. The medication is well-tolerated and does not adversely affect performance on the following day when used at high altitudes to mitigate periodic breathing.[14]
On an interim basis, usually for 7 to 10 days, temazepam is prescribed to address panic and anxiety disorders.[15] In addition to its anticonvulsant effects, temazepam is capable of relaxing skeletal muscles. Temazepam has been utilized in treating nocturnal myoclonus and as a premedication before minimally invasive surgery.[16][17] Furthermore, it is essential to exercise caution in any off-label use of temazepam, considering box warnings and the potential for misuse.
Mechanism of Action
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Mechanism of Action
Temazepam induces central nervous system (CNS) depression by affecting the limbic, thalamic, and hypothalamic regions.[7] Temazepam exerts its pharmacological effects, including drowsiness, hypnosis, skeletal muscle relaxation, anticonvulsant action, and anxiolysis, by binding to benzodiazepine receptors. These receptors constitute several GABA-A receptor subtypes, with a particular affinity for α1 subunits.[18]
Benzodiazepines increase chloride ion influx, leading to neuronal membrane hyperpolarization and reduced neuronal excitability. The hyperpolarized state of the cell membrane impedes further excitation of the associated neurons, as binding enhances the aforementioned chloride ion conduction, manifested through an increased frequency of the chloride channel opening.[7] In a study on rats, temazepam was observed to modulate the hypothalamic-pituitary-adrenal (HPA) axis by altering GABA-A receptors and elevating vasopressin levels in the hypothalamus.[19]
Temazepam administration induces a dose-dependent increase in vasopressin release, while levels of plasma neuropeptides remain unchanged in response to stress. As a result, temazepam demonstrates a dual mechanism of action in suppressing HPA axis activity—directly through the modulation of GABA-A receptors and indirectly by elevating vasopressin concentrations within the hypothalamus. Temazepam was associated with decreased systolic blood pressure and increased heart rate when administered in the morning.[20] Benzodiazepines, including temazepam, increase the frequency of chloride channel opening, whereas barbiturates prolong the opening duration of chloride channels.[21][22]
Pharmacokinetics
Absorption: Temazepam is efficiently absorbed after oral administration, with a minimal first-pass metabolism of only 8%. The time to reach peak plasma concentration (Tmax) varies between 1.2 and 1.6 hours, with an average Tmax of 1.5 hours after administration.[23]
Distribution: Temazepam has a recorded mean volume of distribution of 1.40 L/kg, which does not vary with age or sex.[24][25] Temazepam exhibits a high plasma protein binding capacity, typically around 96%.[26]
Metabolism: Temazepam is eliminated from the body through direct glucuronide conjugation, with the resulting conjugate, temazepam glucuronide, being excreted in the urine.[27] A significantly smaller proportion undergoes parallel oxidation, leading to the formation of oxazepam. Oxazepam is then conjugated to oxazepam glucuronide, which is ultimately eliminated in the urine.[28] Individuals diagnosed with cirrhosis may encounter a prolonged onset of temazepam's hypnotic properties. However, the drug's clearance and accumulation profiles are identical to those of healthy individuals of similar sex and age.[29]
Most unmodified temazepam is promptly converted to glucuronide and is subsequently excreted in the urine, highlighting the pivotal role of the liver in the drug's metabolism. Temazepam's O-conjugate emerges as the most abundant metabolite in the body.[30] There is no evidence to suggest that the glucuronides of temazepam have any activity on the CNS. Temazepam is hypothesized to lack interactions with CYP450 and primarily metabolizes through phase II conjugation reactions.[31] Although the mechanism underlying this occurrence remains unknown, several hypotheses have been proposed. The symptoms of liver injury could be masked if there is a substantial reserve of glucuronyl transferase intra- or extra-hepatically. Glucuronyl transferase may be less susceptible to liver damage. In addition, due to the high affinity of glucuronyl transferases for ATP, glucuronidation is protected in low-ATP environments, albeit potentially at the expense of processes mediated by other enzymes.[32]
Elimination: Research on temazepam clearance has revealed values of 1.03 mL/min/kg for total temazepam and 31 mL/min/kg for unbound temazepam. Notably, 80% to 90% of a single dose of temazepam is excreted in the urine, primarily as the O-conjugate metabolite. In contrast, only 3% to 13% is eliminated in the feces. N-desmethyl temazepam and unmodified temazepam account for less than 2% of the dose eliminated in the urine.[2] Temazepam displays a biphasic elimination pattern. In cases of drugs exhibiting such a pattern, the clinically relevant half-life aligns with the second phase, commonly referred to as the terminal half-life.[33] According to the FDA-approved product labeling, the terminal half-life of temazepam ranges from 3.5 to 18.4 hours, with an average of 8.8 hours.[34] The half-life can be prolonged in older adults and individuals with preexisting medical conditions.
Administration
Available Dosage Forms and Strengths
Temazepam is a white, crystalline drug with a powdery consistency and a moderate degree of solubility in water, whereas alcohol permits only a limited solubility for temazepam.[35] Temazepam is available in liquid, gel, or powder forms and packaged in either hard or soft capsules.[2]
The available dosage strengths of temazepam include 7.5 mg, 10 mg, 15 mg, 20 mg, and 30 mg.[35][10][36] United States Pharmacopeia (USP) capsules are formulated in 7.5 mg, 15 mg, 22.5 mg, and 30 mg for oral administration.
Adult Dosage
According to the task force of the American Academy of Sleep Medicine, there is limited evidence supporting the use of temazepam for sleep onset and sleep maintenance insomnia in adults when compared to no treatment. The recommended dose of temazepam is 15 mg, with the option to increase to 30 mg based on the therapeutic response. Polysomnography results indicated that the temazepam group experienced a significantly shorter sleep latency. Subjective sleep latency was also reduced, and total sleep time increased based on polysomnography analysis. According to the subjective assessment, the use of temazepam resulted in an increase in the total duration of sleep. These findings suggest notable improvements in sleep latency and total sleep time attributed to temazepam use, as observed through both objective and subjective measurements.[37]
Specific Patient Populations
Renal impairment: The product labeling does not provide instructions for adjusting the temazepam dosage for renal impairment.
Hepatic impairment: The product labeling does not provide instructions for adjusting the temazepam dosage for renal impairment.
Pregnancy considerations: Temazepam should be avoided by pregnant women, as it is classified as an FDA pregnancy category X drug. If the medication is used during pregnancy or if the patient becomes pregnant while taking it, the potential fetal risks should be thoroughly discussed with the patient. When administered to a pregnant woman, temazepam can cause fetal harm. Damen et al reported a potentially fatal outcome when a mother of a newborn child took 20 mg of temazepam. The delivery was rapid, and the newborn exhibited signs of being blue, weak, and unresponsive.[38]
Elevated rates of embryonic resorptions were observed at 30 and 120 mg/kg dosages, whereas a higher incidence of rudimentary ribs was noted at 240 mg/kg or above dosages. Exencephaly and fusion or asymmetry of the ribs were also observed, with no discernible correlation to dosage.[39] In an animal study, the administration of oral dosages of temazepam at 60 mg/kg/d led to an observed increase in newborn mortality rates. It is crucial to closely monitor newborns exposed to temazepam during prenatal development for potential complications, including feeding difficulties, respiratory depression, sedation, and withdrawal symptoms. Floppy infant syndrome is associated with benzodiazepines used during pregnancy and is characterized by hypotonia, lethargy, and respiratory depression.[40]
Breastfeeding considerations: Due to the low levels of temazepam found in breastmilk, the amounts consumed by the infant are minimal and are not expected to cause any adverse effects. Taking the bedtime dose after the infant's last feeding of the day may decrease the dose received by an infant who sleeps through the night. Monitoring the infant for signs of drowsiness, poor weight gain, and reduced feeding is recommended.[4]
Pediatric patients: The safety and effectiveness of temazepam in pediatric patients have not been established.
Older patients: The American Geriatrics Society Beers Criteria (2023) emphasizes the avoidance of benzodiazepines, including temazepam, due to their association with increased risks of delirium, cognitive decline, falls, fractures, and motor vehicle accidents in older individuals. However, the American Geriatric Society acknowledges that benzodiazepines may be deemed appropriate for specific conditions, such as seizure disorders, periprocedural anesthesia, benzodiazepine withdrawal, severe generalized anxiety disorder, alcohol withdrawal, and REM sleep disorder. As previously explained, due to the heightened risk of oversedation, dizziness, disorientation, ataxia, and falls associated with higher doses of benzodiazepines in older patients, it is advisable to initiate treatment with a lower dosage of temazepam at 7.5 mg for individuals 65 and older.[2][41]
Adverse Effects
Adverse Drug Reactions
A post-marketing surveillance study was conducted to investigate the adverse effects of temazepam. The study included a sample of 10,057 patients who were administered a 40- to 60-mg dosage for 2 weeks and another group of 8043 patients who received the exact dosage for 3 months. The observed prevalence rate of hangovers in these patient groups was 7%. Furthermore, numerous adverse effects have been documented across various organ systems. Complaints about the cardiovascular system included palpitations, whereas gastrointestinal symptoms included xerostomia, dysgeusia, emesis, diarrhea, epigastric discomfort, and constipation. Neurological symptoms included headache, disorientation, drowsiness, dizziness, giddiness, unsteadiness, anterograde amnesia, and paresthesia. Commonly mentioned psychiatric symptoms included vivid dreams, nightmares, and depression. Temazepam can adversely impact social and mental health and cause violent outbursts at home and in public and psychological disorders, including paranoia and other irrational behaviors.[42][43]
Drug-Drug Interactions
The concomitant administration of temazepam with opioid prescriptions, alcohol, or other CNS depressants can lead to significant drowsiness, respiratory depression, unconsciousness, and even fatality. Lingering effects on psychomotor and cognitive abilities may result in impaired driving ability and potentially higher risks of falling and hip fractures. Furthermore, the activity of temazepam can be disrupted by the concurrent use of barbiturates, nonselective monoamine oxidase inhibitors, phenothiazines, antipsychotics, skeletal muscle relaxants, and antihistamines.[6][44][45]
In relation to alcohol, a study compared blood concentrations of 80 to 100 mg/100 mL of ethanol with those of 20 mg and 30 mg of temazepam in terms of psychomotor speed, accuracy, and long-term memory. Ethanol and 30 mg of temazepam exhibited similar effects on information processing capacity and long-term memory formation. However, ethanol had a significantly distinct impact on psychomotor performance compared to temazepam, leading to faster but more error-prone behavior.[46]
Contraindications
Temazepam is contraindicated in pregnancy, as it is classified as an FDA pregnancy category X drug.[34]
Box Warnings
Similar to all other oral benzodiazepines, temazepam carries a boxed warning on the product label emphasizing the risks of severe sedation and potentially fatal respiratory depression when combined with opioids.[47]
The potential for abuse, misuse, and addiction associated with temazepam increases the risk of overdose or fatality. Before prescribing temazepam and throughout treatment, the risk of abuse, misuse, and addiction in each patient should be evaluated. Intravenous administration is the main method of abuse for temazepam capsules.[48] The adverse effects of temazepam intravenously include venous and arterial thrombosis, compartment syndrome, gangrene, and rhabdomyolysis.[49][50]
Temazepam, often combined with buprenorphine in a "cocktail," may increase the risk of overdose.[51] Individuals who use temazepam are more likely to share needles, putting themselves and others at risk of contracting hepatitis and HIV. Consequently, many manufacturers have transitioned from producing liquid-filled capsules to manufacturing tablets and gel. However, users discovered that the gel could be melted with a hot needle, making it easier to inject.[50][42]
Developing a tolerance to temazepam is possible, especially if it is used for a moderate-to-long period. Symptoms and signs of temazepam withdrawal may include agitation, irritability, dysphoria, depersonalization, twitching, muscle cramps and discomfort, weakness, ataxia, headache, hypersensitivity to lights and other stimuli, nausea, sweating, and vomiting. Acute delirium, characterized by impaired attention and cognition, may be an ominous sign of temazepam withdrawal. Disruptions in sleep and mood have been identified as signs of withdrawal tolerance.
The mechanism of discontinuation from temazepam is the same as that of any other benzodiazepine. Abrupt discontinuation of continuous treatment with benzodiazepines may lead to withdrawal or rebound syndrome. In contrast to a sole increase in benzodiazepine binding sites, an augmentation in the number of binding sites for both benzodiazepines and chloride-channel ligands suggests that the available number of GABA-A receptor complexes is heightened following benzodiazepine discontinuation.[52] Sleep lab studies have confirmed rebound insomnia following the sudden cessation of short-term, therapeutic benzodiazepine use as a hypnotic or anxiolytic. Temazepam induces rebound insomnia after abrupt discontinuation, which can contribute to relapse and continued drug use.[53][54]
Precautions
The use of temazepam should be minimized or entirely avoided in individuals with severe motor coordination impairment, acute intoxication with alcohol, opioids, or other psychoactive substances, sleep apnea, myasthenia gravis, acute narrow-angle glaucoma, clinically significant major depressive disorder with suicidal ideation, renal and hepatic insufficiency, hypersensitivity, or allergy to any benzodiazepines.[55][56]
Monitoring
Healthcare professionals, including physicians, nurses, and pharmacists, must have a comprehensive understanding of the advantages and drawbacks associated with using temazepam as a therapeutic intervention for insomnia. Patients should only use temazepam, a benzodiazepine, for short-term sleep management, and this limitation should be communicated to them. In addition, patients should be aware that temazepam will be gradually tapered over a specific period to mitigate the risk of precipitating an acute withdrawal syndrome, which can lead to severe medical and neuropsychiatric complications.
Patients must also be educated about temazepam alternatives. Instead of relying on a one-size-fits-all strategy, promoting lifestyle changes and creating an environment that encourages physical activity and healthy sleep habits can help address sleep disorders and improve sleep quality. A multiapproach should be considered to address sleep problems effectively and choose the optimal treatment option. Integrating the patient, family, pharmacy, substance abuse counselor, addiction specialist, sleep specialist, and other healthcare providers is essential for creating a healthier path in treating sleep disorders. Thus, a balanced approach involving all relevant parties should be weighed with the patient's well-being in mind.
Healthcare practitioners should consistently monitor their patients for temazepam misuse and provide education about the potential risks. Prescription drug monitoring programs can assist in monitoring potential misuse.[57] In a study involving older veterans with insomnia, approximately half were found to have undiagnosed sleep-disordered breathing.[58] Polysomnography should be considered on an individual basis when sleep-related breathing disorders, such as obstructive or central sleep apnea, nocturnal seizures, periodic limb movement disorder, REM sleep disorder, and narcolepsy, are suspected.[59] Screening for underlying anxiety and depression should also be considered in patients in case of inadequate therapeutic response.[60] Clinicians can assess disease severity using tools such as the Insomnia Severity Index (ISI).[61][62]
Toxicity
Signs and Symptoms of Overdose
Deaths from self-poisoning with temazepam alone or in combination with other substances were shown to be more common than with any other benzodiazepines except flurazepam, which had the highest mortality rate per million prescriptions. It has been claimed that disulfiram can hasten temazepam's toxicity by heightening the depression of the CNS.[2] Acute overdosing on temazepam, like other benzodiazepines, manifests in sleepiness, confusion, and coma.
Moreover, it has been observed that overdoses of temazepam and zopiclone/zolpidem are more prone to fatalities compared to diazepam overdoses. Temazepam was found to be 10 times more hazardous than diazepam, whereas zopiclone, eszopiclone, zaleplon, and zolpidem (Z-drugs) were each just 9 times more toxic than diazepam.[45] Temazepam has been associated with higher toxicity than other benzodiazepines in studies of intentional self-poisoning in a large national sample of veterans prescribed opioid analgesics.[63] However, temazepam was linked to a lower overdose mortality rate than clonazepam.[64] The oral LD50 of temazepam was 1963 mg/kg in mice, 1833 mg/kg in rats, and >2400 mg/kg in rabbits.
Management of Overdose
Temazepam overdose therapy involves supportive care, including airway, breathing, and circulatory examinations. Complex cases may require intensive care unit admission. The Poison Control Center can be contacted for assistance in complicated poisoning cases.[65] The sedative effects of temazepam can be counteracted by flumazenil—a nonspecific competitive antagonist at the benzodiazepine receptor.[66]
Enhancing Healthcare Team Outcomes
The sleep-wake cycle is a multifaceted phenomenon that involves several physiological and behavioral fluctuations.[67][68] Epigenetic occurrences play a significant role in regulating sleep homeostasis and circadian rhythms, contributing to the understanding of the pathogenesis of sleep disorders such as sleep apnea, insomnia, sleep deprivation, and associated comorbidities.[69][70] Sleep dysfunction, which includes insufficient sleep length and poor sleep quality, has been associated with various negative health outcomes, including hypertension, diabetes, cancer, anxiety, and major depressive disorder.[71][72][73] Sleepiness and exhaustion resulting from insufficient sleep during wakefulness can impair performance and productivity, leading to absenteeism and an increased risk of work-related accidents.[74][75]
Quality of life is multifaceted, consisting of various physical, psychological, and social dimensions. Research has demonstrated that both lower sleep quantity and poor sleep quality have damaging effects on these dimensions.[76][77] As noted above, insomnia frequently coexists with certain primary sleep disorders such as restless legs syndrome, periodic limb movement disorders, and sleep-related breathing disorders, which require referral to sleep medicine specialists.[78] Medical disorders leading to insomnia, such as hyperthyroidism, should be ruled out.[79] The decision to initiate temazepam should be carefully evaluated, considering medical and neuropsychiatric issues, as well as the potential to improve overall quality of life.
The use of benzodiazepines as pharmacological therapies for treating sleep-related disorders has received a lot of attention lately. Temazepam, a benzodiazepine, belongs to the same category and carries similar risks for patients, such as overdose, respiratory depression, falls, abuse, misuse, and addiction. Therefore, physicians, advanced practitioners, nurses, pharmacists, and other health professionals must be well-versed and knowledgeable of the mechanism of action of temazepam, adverse effects, and strategies to mitigate complications that can lead to adverse outcomes. Pharmacists should conduct medication reconciliation and verify that opioids have not been co-prescribed with temazepam. Nurses should monitor the response to therapy and alert the team about adherence and potential signs of misuse.
Persistent insomnia that does not respond to temazepam necessitates referral to a psychiatrist. Patients should receive counseling on the appropriate use of temazepam and be closely monitored for indications and symptoms of abuse, misuse, and drug use disorder. Early treatment should be initiated for individuals with a high suspicion that they are developing a substance use issue, and they should be referred to addiction medicine specialists. Severe poisoning may require admission to the Medical Intensive Care Unit (MICU) under the supervision of critical care physicians.
The sudden cessation of temazepam can also induce severe and possibly life-threatening medical problems. Before initiating temazepam for a patient, a comprehensive assessment should consider its advantages, disadvantages, and alternative options carefully. The physician-patient connection, the involvement of the patient's family, and the support system should be considered while making such a decision. The incorporation of the concepts of beneficence and autonomy is crucial when making such a decision. An interprofessional team approach involving clinicians (MDs, DOs, NPs, and PAs), specialists, nurses, and pharmacists is essential for optimal use of temazepam for insomnia.
References
Mitler MM. Evaluation of temazepam as a hypnotic. Pharmacotherapy. 1981 Jul-Aug:1(1):3-13 [PubMed PMID: 6152815]
. Temazepam. IARC monographs on the evaluation of carcinogenic risks to humans. 1996:66():161-73 [PubMed PMID: 9097124]
Level 3 (low-level) evidence. Temazepam. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012:(): [PubMed PMID: 31643873]
. Temazepam. Drugs and Lactation Database (LactMed®). 2006:(): [PubMed PMID: 30000315]
Ralston GE, Taylor JA. Temazepam abuse. Addiction (Abingdon, England). 1993 Mar:88(3):423 [PubMed PMID: 8461860]
Level 3 (low-level) evidencePreuss CV, Kalava A, King KC. Prescription of Controlled Substances: Benefits and Risks. StatPearls. 2023 Jan:(): [PubMed PMID: 30726003]
Fraschini F, Stankov B. Temazepam: pharmacological profile of a benzodiazepine and new trends in its clinical application. Pharmacological research. 1993 Feb-Mar:27(2):97-113 [PubMed PMID: 8474963]
Level 3 (low-level) evidence. Temazepam for insomnia? Drug and therapeutics bulletin. 1978 Mar 17:16(6):21-2 [PubMed PMID: 631020]
Bixler EO, Kales A, Soldatos CR, Scharf MB, Kales JD. Effectiveness of temazepam with short-intermediate-, and long-term use: sleep laboratory evaluation. Journal of clinical pharmacology. 1978 Feb-Mar:18(2-3):110-8 [PubMed PMID: 342551]
Mitler MM, Carskadon MA, Phillips RL, Sterling WR, Zarcone VP Jr, Spiegel R, Guilleminault C, Dement WC. Hypnotic efficacy of temazepam: a long-term sleep laboratory evaluation. British journal of clinical pharmacology. 1979:8(1):63S-68S [PubMed PMID: 41543]
Level 1 (high-level) evidenceMorgenthaler TI, Lee-Chiong T, Alessi C, Friedman L, Aurora RN, Boehlecke B, Brown T, Chesson AL Jr, Kapur V, Maganti R, Owens J, Pancer J, Swick TJ, Zak R, Standards of Practice Committee of the American Academy of Sleep Medicine. Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep. 2007 Nov:30(11):1445-59 [PubMed PMID: 18041479]
Nicholson AN, Stone BM. Hypnotics and transient insomnia. Acta psychiatrica Scandinavica. Supplementum. 1986:332():55-9 [PubMed PMID: 2883829]
Arendt J. Approaches to the Pharmacological Management of Jet Lag. Drugs. 2018 Sep:78(14):1419-1431. doi: 10.1007/s40265-018-0973-8. Epub [PubMed PMID: 30167980]
Nickol AH, Leverment J, Richards P, Seal P, Harris GA, Cleland J, Dubowitz G, Collier DJ, Milledge J, Stradling JR, Morrell MJ. Temazepam at high altitude reduces periodic breathing without impairing next-day performance: a randomized cross-over double-blind study. Journal of sleep research. 2006 Dec:15(4):445-54 [PubMed PMID: 17118102]
Level 1 (high-level) evidenceRoehrs T, Vogel G, Vogel F, Wittig R, Zorick F, Paxton C, Lamphere J, Roth T. Dose effects of temazepam tablets on sleep. Drugs under experimental and clinical research. 1986:12(8):693-9 [PubMed PMID: 2875858]
Mitler MM, Browman CP, Menn SJ, Gujavarty K, Timms RM. Nocturnal myoclonus: treatment efficacy of clonazepam and temazepam. Sleep. 1986:9(3):385-92 [PubMed PMID: 2876485]
Level 1 (high-level) evidenceAmarasekera K. Temazepam as a premedicant in minor surgery. Anaesthesia. 1980 Aug:35(8):771-4 [PubMed PMID: 6108729]
Level 1 (high-level) evidenceOelschläger H. [Chemical and pharmacologic aspects of benzodiazepines]. Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis. 1989 Jul 4:78(27-28):766-72 [PubMed PMID: 2570451]
Welt T, Engelmann M, Renner U, Erhardt A, Müller MB, Landgraf R, Holsboer F, Keck ME. Temazepam triggers the release of vasopressin into the rat hypothalamic paraventricular nucleus: novel insight into benzodiazepine action on hypothalamic-pituitary-adrenocortical system activity during stress. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2006 Dec:31(12):2573-9 [PubMed PMID: 16395302]
Level 3 (low-level) evidenceFord GA, Hoffman BB, Blaschke TF. Effect of temazepam on blood pressure regulation in healthy elderly subjects. British journal of clinical pharmacology. 1990 Jan:29(1):61-7 [PubMed PMID: 1967533]
Level 1 (high-level) evidenceGoldschen-Ohm MP. Benzodiazepine Modulation of GABA(A) Receptors: A Mechanistic Perspective. Biomolecules. 2022 Nov 30:12(12):. doi: 10.3390/biom12121784. Epub 2022 Nov 30 [PubMed PMID: 36551212]
Level 3 (low-level) evidenceBianchi MT, Botzolakis EJ, Lagrange AH, Macdonald RL. Benzodiazepine modulation of GABA(A) receptor opening frequency depends on activation context: a patch clamp and simulation study. Epilepsy research. 2009 Aug:85(2-3):212-20. doi: 10.1016/j.eplepsyres.2009.03.007. Epub 2009 May 15 [PubMed PMID: 19447010]
Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner journal. 2013 Summer:13(2):214-23 [PubMed PMID: 23789008]
Ochs HR, Greenblatt DJ, Heuer H. Is temazepam an accumulating hypnotic? Journal of clinical pharmacology. 1984 Jan:24(1):58-64 [PubMed PMID: 6142905]
Divoll M, Greenblatt DJ, Harmatz JS, Shader RI. Effect of age and gender on disposition of temazepam. Journal of pharmaceutical sciences. 1981 Oct:70(10):1104-7 [PubMed PMID: 6117653]
E Eleraky N, M Omar M, A Mahmoud H, A Abou-Taleb H. Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study. Pharmaceutics. 2020 May 14:12(5):. doi: 10.3390/pharmaceutics12050451. Epub 2020 May 14 [PubMed PMID: 32422903]
Marland A, Sarkar P, Leavitt R. The urinary elimination profiles of diazepam and its metabolites, nordiazepam, temazepam, and oxazepam, in the equine after a 10-mg intramuscular dose. Journal of analytical toxicology. 1999 Jan-Feb:23(1):29-34 [PubMed PMID: 10022206]
Level 3 (low-level) evidenceLocniskar A, Greenblatt DJ. Oxidative versus conjugative biotransformation of temazepam. Biopharmaceutics & drug disposition. 1990 Aug-Sep:11(6):499-506 [PubMed PMID: 2207300]
Ochs HR, Greenblatt DJ, Verburg-Ochs B, Matlis R. Temazepam clearance unaltered in cirrhosis. The American journal of gastroenterology. 1986 Jan:81(1):80-4 [PubMed PMID: 2867675]
CHILDRESS SJ, GLUCKMAN MI. 1,4-BENZODIAZEPINES. Journal of pharmaceutical sciences. 1964 Jun:53():577-90 [PubMed PMID: 14198427]
English BA, Dortch M, Ereshefsky L, Jhee S. Clinically significant psychotropic drug-drug interactions in the primary care setting. Current psychiatry reports. 2012 Aug:14(4):376-90. doi: 10.1007/s11920-012-0284-9. Epub [PubMed PMID: 22707017]
Ghabrial H, Desmond PV, Watson KJ, Gijsbers AJ, Harman PJ, Breen KJ, Mashford ML. The effects of age and chronic liver disease on the elimination of temazepam. European journal of clinical pharmacology. 1986:30(1):93-7 [PubMed PMID: 2872062]
Andrade C. The Practical Importance of Half-Life in Psychopharmacology. The Journal of clinical psychiatry. 2022 Jul 25:83(4):. pii: 22f14584. doi: 10.4088/JCP.22f14584. Epub 2022 Jul 25 [PubMed PMID: 35900254]
Lie JD, Tu KN, Shen DD, Wong BM. Pharmacological Treatment of Insomnia. P & T : a peer-reviewed journal for formulary management. 2015 Nov:40(11):759-71 [PubMed PMID: 26609210]
McElnay JC, Jones ME, Alexander B. Temazepam (Restoril, Sandoz Pharmaceuticals). Drug intelligence & clinical pharmacy. 1982 Sep:16(9):650-6 [PubMed PMID: 6127197]
Level 3 (low-level) evidenceBeary MD, Lacey JH, Crutchfield MB, Bhat AV. Psycho-social stress, insomnia and temazepam: a sleep laboratory evaluation in a "general practice" sample. Psychopharmacology. 1984:83(1):17-9 [PubMed PMID: 6146153]
Level 1 (high-level) evidenceSateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2017 Feb 15:13(2):307-349. doi: 10.5664/jcsm.6470. Epub 2017 Feb 15 [PubMed PMID: 27998379]
Level 1 (high-level) evidenceDamen L, Visser DH, Sie SD, van Weissenbruch MM. Apparent Life-Threatening Event following Maternal Use of Temazepam during Labour. Case reports in pediatrics. 2014:2014():650605. doi: 10.1155/2014/650605. Epub 2014 Jun 15 [PubMed PMID: 25024861]
Level 3 (low-level) evidenceCreeley CE, Denton LK. Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes. Brain sciences. 2019 Sep 14:9(9):. doi: 10.3390/brainsci9090235. Epub 2019 Sep 14 [PubMed PMID: 31540060]
Level 1 (high-level) evidenceBrandlistuen RE, Ystrom E, Hernandez-Diaz S, Skurtveit S, Selmer R, Handal M, Nordeng H. Association of prenatal exposure to benzodiazepines and child internalizing problems: A sibling-controlled cohort study. PloS one. 2017:12(7):e0181042. doi: 10.1371/journal.pone.0181042. Epub 2017 Jul 26 [PubMed PMID: 28746341]
By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. 2023 Jul:71(7):2052-2081. doi: 10.1111/jgs.18372. Epub 2023 May 4 [PubMed PMID: 37139824]
Ruben SM, Morrison CL. Temazepam misuse in a group of injecting drug users. British journal of addiction. 1992 Oct:87(10):1387-92 [PubMed PMID: 1422104]
Fowler LK. Post-marketing surveillance of Euhypnos (temazepam): a new hypnotic. The Journal of international medical research. 1980:8(4):295-9 [PubMed PMID: 6105982]
Pham Nguyen TP, Soprano SE, Hennessy S, Brensinger CM, Bilker WB, Miano TA, Acton EK, Horn JR, Chung SP, Dublin S, Oslin DW, Wiebe DJ, Leonard CE. Population-based signals of benzodiazepine drug interactions associated with unintentional traumatic injury. Journal of psychiatric research. 2022 Jul:151():299-303. doi: 10.1016/j.jpsychires.2022.04.033. Epub 2022 May 1 [PubMed PMID: 35526445]
Geulayov G, Ferrey A, Casey D, Wells C, Fuller A, Bankhead C, Gunnell D, Clements C, Kapur N, Ness J, Waters K, Hawton K. Relative toxicity of benzodiazepines and hypnotics commonly used for self-poisoning: An epidemiological study of fatal toxicity and case fatality. Journal of psychopharmacology (Oxford, England). 2018 Jun:32(6):654-662. doi: 10.1177/0269881118754734. Epub 2018 Feb 14 [PubMed PMID: 29442611]
Level 2 (mid-level) evidenceTiplady B, Hiroz J, Holmes L, Drummond G. Errors in performance testing: a comparison of ethanol and temazepam. Journal of psychopharmacology (Oxford, England). 2003 Mar:17(1):41-9 [PubMed PMID: 12680738]
Level 1 (high-level) evidenceVadiei N, Bhattacharjee S. Concurrent Opioid and Benzodiazepine Utilization Patterns and Predictors Among Community-Dwelling Adults in the United States. Psychiatric services (Washington, D.C.). 2020 Oct 1:71(10):1011-1019. doi: 10.1176/appi.ps.201900446. Epub 2020 Jun 10 [PubMed PMID: 32517642]
Lader M. Anxiolytic drugs: dependence, addiction and abuse. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 1994 Jun:4(2):85-91 [PubMed PMID: 7919947]
Dobbin M, Martyres RF, Clode D, Champion De Crespigny FE. Association of benzodiazepine injection with the prescription of temazepam capsules. Drug and alcohol review. 2003 Jun:22(2):153-7 [PubMed PMID: 12850901]
Scott RN, Going J, Woodburn KR, Gilmour DG, Reid DB, Leiberman DP, Maraj B, Pollock JG. Intra-arterial temazepam. BMJ (Clinical research ed.). 1992 Jun 20:304(6842):1630 [PubMed PMID: 1628096]
Level 3 (low-level) evidenceForsyth AJ, Farquhar D, Gemmell M, Shewan D, Davies JB. The dual use of opioids and temazepam by drug injectors in Glasgow (Scotland). Drug and alcohol dependence. 1993 May:32(3):277-80 [PubMed PMID: 8348877]
Level 2 (mid-level) evidenceMiller LG, Greenblatt DJ, Roy RB, Summer WR, Shader RI. Chronic benzodiazepine administration. II. Discontinuation syndrome is associated with upregulation of gamma-aminobutyric acidA receptor complex binding and function. The Journal of pharmacology and experimental therapeutics. 1988 Jul:246(1):177-82 [PubMed PMID: 2455789]
Level 3 (low-level) evidenceKales A, Bixler EO, Soldatos CR, Vela-Bueno A, Jacoby JA, Kales JD. Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal. Clinical pharmacology and therapeutics. 1986 Mar:39(3):345-52 [PubMed PMID: 2868823]
Kales A, Manfredi RL, Vgontzas AN, Bixler EO, Vela-Bueno A, Fee EC. Rebound insomnia after only brief and intermittent use of rapidly eliminated benzodiazepines. Clinical pharmacology and therapeutics. 1991 Apr:49(4):468-76 [PubMed PMID: 2015735]
Level 1 (high-level) evidenceEdinoff AN, Nix CA, Hollier J, Sagrera CE, Delacroix BM, Abubakar T, Cornett EM, Kaye AM, Kaye AD. Benzodiazepines: Uses, Dangers, and Clinical Considerations. Neurology international. 2021 Nov 10:13(4):594-607. doi: 10.3390/neurolint13040059. Epub 2021 Nov 10 [PubMed PMID: 34842811]
Lader M. Benzodiazepine harm: how can it be reduced? British journal of clinical pharmacology. 2014 Feb:77(2):295-301. doi: 10.1111/j.1365-2125.2012.04418.x. Epub [PubMed PMID: 22882333]
Calcaterra SL, Butler M, Olson K, Blum J. The Impact of a PDMP-EHR Data Integration Combined With Clinical Decision Support on Opioid and Benzodiazepine Prescribing Across Clinicians in a Metropolitan Area. Journal of addiction medicine. 2022 May-Jun 01:16(3):324-332. doi: 10.1097/ADM.0000000000000905. Epub [PubMed PMID: 34392255]
Fung CH, Martin JL, Dzierzewski JM, Jouldjian S, Josephson K, Park M, Alessi C. Prevalence and symptoms of occult sleep disordered breathing among older veterans with insomnia. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2013 Nov 15:9(11):1173-8. doi: 10.5664/jcsm.3162. Epub 2013 Nov 15 [PubMed PMID: 24235899]
Rundo JV, Downey R 3rd. Polysomnography. Handbook of clinical neurology. 2019:160():381-392. doi: 10.1016/B978-0-444-64032-1.00025-4. Epub [PubMed PMID: 31277862]
Irwin MR, Carrillo C, Sadeghi N, Bjurstrom MF, Breen EC, Olmstead R. Prevention of Incident and Recurrent Major Depression in Older Adults With Insomnia: A Randomized Clinical Trial. JAMA psychiatry. 2022 Jan 1:79(1):33-41. doi: 10.1001/jamapsychiatry.2021.3422. Epub [PubMed PMID: 34817561]
Level 1 (high-level) evidenceMichaud AL, Zhou ES, Chang G, Recklitis CJ. Validation of the Insomnia Severity Index (ISI) for identifying insomnia in young adult cancer survivors: comparison with a structured clinical diagnostic interview of the DSM-5 (SCID-5). Sleep medicine. 2021 May:81():80-85. doi: 10.1016/j.sleep.2021.01.045. Epub 2021 Feb 4 [PubMed PMID: 33640841]
Level 1 (high-level) evidenceMorin CM, Belleville G, Bélanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011 May 1:34(5):601-8 [PubMed PMID: 21532953]
Level 3 (low-level) evidenceBuckley NA, Dawson AH, Whyte IM, O'Connell DL. Relative toxicity of benzodiazepines in overdose. BMJ (Clinical research ed.). 1995 Jan 28:310(6974):219-21 [PubMed PMID: 7866122]
Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert AS. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ (Clinical research ed.). 2015 Jun 10:350():h2698. doi: 10.1136/bmj.h2698. Epub 2015 Jun 10 [PubMed PMID: 26063215]
Level 3 (low-level) evidenceFarkas A, Kostic M, Huang CC, Gummin D. Poison center consultation reduces hospital length of stay. Clinical toxicology (Philadelphia, Pa.). 2022 Jul:60(7):863-868. doi: 10.1080/15563650.2022.2039686. Epub 2022 Mar 9 [PubMed PMID: 35261300]
Kang M, Galuska MA, Ghassemzadeh S. Benzodiazepine Toxicity. StatPearls. 2023 Jan:(): [PubMed PMID: 29489152]
Harvey CJ, Gehrman P, Espie CA. Who is predisposed to insomnia: a review of familial aggregation, stress-reactivity, personality and coping style. Sleep medicine reviews. 2014 Jun:18(3):237-47. doi: 10.1016/j.smrv.2013.11.004. Epub 2013 Nov 28 [PubMed PMID: 24480386]
Jarrin DC, Chen IY, Ivers H, Morin CM. The role of vulnerability in stress-related insomnia, social support and coping styles on incidence and persistence of insomnia. Journal of sleep research. 2014 Dec:23(6):681-688. doi: 10.1111/jsr.12172. Epub 2014 Jul 7 [PubMed PMID: 25040302]
Level 2 (mid-level) evidenceCortese R. Epigenetics of Sleep Disorders: An Emerging Field in Diagnosis and Therapeutics. Diagnostics (Basel, Switzerland). 2021 May 10:11(5):. doi: 10.3390/diagnostics11050851. Epub 2021 May 10 [PubMed PMID: 34068472]
Palagini L, Biber K, Riemann D. The genetics of insomnia--evidence for epigenetic mechanisms? Sleep medicine reviews. 2014 Jun:18(3):225-35. doi: 10.1016/j.smrv.2013.05.002. Epub 2013 Aug 7 [PubMed PMID: 23932332]
Briançon-Marjollet A, Weiszenstein M, Henri M, Thomas A, Godin-Ribuot D, Polak J. The impact of sleep disorders on glucose metabolism: endocrine and molecular mechanisms. Diabetology & metabolic syndrome. 2015:7():25. doi: 10.1186/s13098-015-0018-3. Epub 2015 Mar 24 [PubMed PMID: 25834642]
Han B, Chen WZ, Li YC, Chen J, Zeng ZQ. Sleep and hypertension. Sleep & breathing = Schlaf & Atmung. 2020 Mar:24(1):351-356. doi: 10.1007/s11325-019-01907-2. Epub 2019 Aug 12 [PubMed PMID: 31402441]
Medic G, Wille M, Hemels ME. Short- and long-term health consequences of sleep disruption. Nature and science of sleep. 2017:9():151-161. doi: 10.2147/NSS.S134864. Epub 2017 May 19 [PubMed PMID: 28579842]
Caruso CC. Negative impacts of shiftwork and long work hours. Rehabilitation nursing : the official journal of the Association of Rehabilitation Nurses. 2014 Jan-Feb:39(1):16-25. doi: 10.1002/rnj.107. Epub 2013 Jun 18 [PubMed PMID: 23780784]
Walker MP, van der Helm E. Overnight therapy? The role of sleep in emotional brain processing. Psychological bulletin. 2009 Sep:135(5):731-48. doi: 10.1037/a0016570. Epub [PubMed PMID: 19702380]
Amellal M, Binck M, Frossard N, Ilien B, Landry Y. Sodium-potassium ATPase inhibition potentiates compound 48/80-induced histamine secretion from mast cells. British journal of pharmacology. 1984 Jun:82(2):423-30 [PubMed PMID: 6203594]
Level 3 (low-level) evidenceDunleavy G, Tonon AC, Chua AP, Zhang Y, Cheung KL, Thach TQ, Rykov Y, Soh CK, Christopoulos G, de Vries H, Car J. A Multifactorial Approach to Sleep and Its Association with Health-Related Quality of Life in a Multiethnic Asian Working Population: A Cross-Sectional Analysis. International journal of environmental research and public health. 2019 Oct 28:16(21):. doi: 10.3390/ijerph16214147. Epub 2019 Oct 28 [PubMed PMID: 31661849]
Level 2 (mid-level) evidenceRoth T. Insomnia: definition, prevalence, etiology, and consequences. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2007 Aug 15:3(5 Suppl):S7-10 [PubMed PMID: 17824495]
Green ME, Bernet V, Cheung J. Thyroid Dysfunction and Sleep Disorders. Frontiers in endocrinology. 2021:12():725829. doi: 10.3389/fendo.2021.725829. Epub 2021 Aug 24 [PubMed PMID: 34504473]