A 2015 review identifies FDA-approved and off-label hypnotics used for insomnia. Authors do not specifically discuss agents that can be used for NPO patients; however, diphenhydramine, an antihistamine, is a non-FDA-approved option used for insomnia and is available in an IV formulation [1]. Diphenhydramine dosage should be individualized according to the needs and response of the patient. For adults, diphenhydramine should be dosed as 10 to 50 mg intravenously at a rate generally not exceeding 25 mg/min, or deep intramuscularly, 100 mg if required (maximum daily dosage is 400 mg) [2]. Authors in a separate 2015 review mention olanzapine, an atypical antipsychotic, as a potential non-FDA-approved option for treatment of insomnia, which is available in an IV formulation [3]. The sedation associated with olanzapine results from its antagonistic effects on serotonin and histamine receptors. The effects of antipsychotics on sleep have been studied in patients with comorbid conditions, such as depression and psychosis; however, they have not been evaluated in subjects with primary insomnia. Olanzapine prescribing information provides dosing specifically for its FDA-approved indication of agitation associated with schizophrenia and bipolar I mania; off-label dosing for insomnia is not provided [4].
The FDA-approved benzodiazepines for insomnia (flurazepam, quazepam, temazepam and triazolam) are not available in non-oral formulations [1], [2], [3], [4], [5], [6], [7], [8], [9]; however, lorazepam was evaluated in a 2 mg dose using a 16-night protocol including 7 nights of drug trial in an observational study. Initially and with continued use, the drug was modestly effective in inducing and maintaining sleep (with an approximate reduction in total wake time of 20 minutes after 9 days. Withdrawal effects significantly reduced sleep from baseline after discontinuation (increase of approximately 40 minutes of wakefulness, p <0.01) [5]. Lorazepam is available as an IM and IV injection and is indicated in adult patients for preanesthetic medication, producing sedation (sleepiness or drowsiness). For the primary purpose of sedation and relief of anxiety, the usual recommended initial dose of lorazepam for intravenous injection is 2 mg total, or 0.044 mg/kg, whichever is smaller. This dosage will be sedating in most adult patients. However, individualization of dosing, especially in those over 50 years of age should be considered [6].
Additionally, diazepam 10 mg has been evaluated in a sleep laboratory study (N= 6). With initial drug use, authors noted improvement in sleep, and there was little evidence of tolerance developing at the end of the 1-week drug administration period (not quantified) [7]. Diazepam is available as an IM and IV injection for the management of anxiety disorders. While dosing should be individualized for maximum beneficial effect, the initial recommended dose in older children and adults ranges from 2 mg to 20 mg intramuscular or intravenous, depending on the indication and its severity [8].
A study found a single intravenous dose of IV diphenhydramine provided safe and effective sedation in patients with cirrhosis. Sleep of 1 to 2 hr duration was induced in all subjects (n= 9) with a single 0.8 mg/kg IV dose. [10]
A 2016 systematic review analyzed the use of benzodiazepines, nonbenzodiazepine, sedatives, melatonin, propofol, and dexmedetomidine to reduce poor sleep in hospitalized patients (15 studies; N= 861 patients). The reviewers found no consistent trends concerning sleep efficiency, quality or interruptions. No specific agent or class was superior for improved sleep compared to each other or no treatment. Benzodiazepines had some success compared to no treatment with regards to sleep latency; however, this finding was inconsistent among included studies. [11]