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Compounded Preparations for Sleep Deprivation

We are barely three months into the New Year, yet patients may already be complaining of sleep deprivation and exhaustion. With March being National Sleep Month, now is the perfect time to discuss medications to address sleep deprivation. Sleep has a variety of health benefits, including resilience against a number of disease states (like depression) as well as maintaining next-day energy levels. These benefits can in turn help increase weight loss, improve work performance, and decrease social isolation. However, stress from work or even biological processes, such as menopause, may disrupt patients’ sleep schedules. Regardless of the underlying cause, there are a variety of commercially-available and compounded preparations to get patients back on track with a healthy sleep schedule.

Because several drugs call for lower dosages than their commercially-available forms, compounded preparations help tailor the dosage to ensure accurate dosing and maximize a therapy’s effectiveness. Compounding can also be performed to alter the dosage form, which is particularly helpful for patients who have swallowing difficulties, such as older adults. Because any manipulation to a commercially-available medication may drastically alter its release profile or absorption, it’s important that these changes be performed by a licensed compounding pharmacy.

Here are some medications that address sleep deprivation and chronic fatigue.

Low-dose naltrexone 

Although indicated for alcohol use disorder and opioid use disorder, low-dose naltrexone (LDN) has also been shown to assist with chronic fatigue. Some case studies have even suggested that low-dose naltrexone succeeded where previous therapies failed, helping some patients return to their previous quality of life. Several case reports have demonstrated its off-label use to treat fatigue at a dose range of 3 to 12 mg/day. (1,2,3) Because these doses are much lower than the commercially-available dosage form of 50 mg tablets, compounding may be necessary to ensure that patients receive an accurate lower dosage that is tailored to their specific needs.


Trazodone is FDA-approved for treating depression, but it is commonly off-label prescribed for treating insomnia. In fact, this off-label use has now exceeded its use as an antidepressant. (4) Trazodone requires a lower dose to treat insomnia than depression (50 to 150 mg versus 150 to 400 mg, respectively) and can be prescribed as either tablets or an oral solution. As this medication is sold as an extended-release tablet, any manipulations, such as crushing or pill splitting, will alter its release profile. Therefore, if a lower dosage is necessary, it’s important that this change be performed by a licensed 503A compounding pharmacy. 

Magnesium IV therapy

Magnesium (Mg) has been shown to help prevent daytime sleepiness in some patients. Some studies have shown an association between Mg intake and improved sleep quality, but the peer-reviewed literature reveals mixed results. (5) Some studies found an association between Mg intake and sleep quality, but due to study design limitations, the authors were unable to make a causal link. (6) Mg can be administered intravenously to help reduce patient fatigue. 

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Cannabidiol (CBD)

CBD affects the endocannabinoid system, which is responsible for homeostasis and regulates a variety of functions, including appetite, memory, and sleep. Some studies have shown a moderate benefit to the use of CBD to improve sleep. A 2019 study showed that about 66 percent of patients’ sleep improved within the first month of CBD usage, but the effect fluctuated over time. (7) CBD can be administered via topical, sublingual, buccal, or oral mucosal routes. As this is a potentially unregulated area, it is best to source CBD from a licensed pharmacy or medical provider to ensure quality and safety. 


Although melatonin is available as an OTC supplement, recent recalls and a JAMA study showed that the majority of analyzed melatonin gummy products do not contain melatonin within specified limits. This highlights the importance of prescribing quality supplements sourced from a trusted pharmacy. VLS Pharmacy & New Drug Loft sells our own brand of melatonin called Metagenics as well as our own supplement line called Revitalized Health. 

Melatonin receptor agonists

Melatonin receptor agonists are often more potent than melatonin itself, with better pharmacokinetics and longer half-lives. 

  • Ramelteon  

Ramelteon was the first melatonin receptor agonist to receive FDA approval for treating insomnia. Since then, additional studies have continued to confirm its benefits for treating sleep disorders. (8) A recent meta-analysis showed that ramelteon moderately improved sleep time, sleep latency, and sleep quality in older patients, who often lack safe and effective options for treating their insomnia. (9) Because older adults often have difficulty swallowing pills, compounding can be performed to change the dosage form to facilitate swallowing. 

  • Tasimelteon

Tasimelteon is an agonist of the melatonin MT1 and MT2 receptors that has received FDA approval for non-24-hour sleep-wake disorder. A long-term pooled analysis of several clinical trials showed that tasimelteon was safe and well-tolerated (10) and did not induce next-day drowsiness, a common side effect of melatonin. (11)


Progesterone levels decrease as patients age, especially once menopause occurs. Low levels of this hormone have been associated with poor sleep, including sleep apnea and insomnia. As part of our compounded bioidentical hormone replacement therapy (BHRT) preparations, we offer progesterone therapy for treating sleep deprivation caused by menopausal and post-menopausal symptoms. Although various explanations exist for why progesterone improves sleep in this population, it is generally considered effective for treating sleep disturbances in menopausal women. (12)


A variety of medications are prescribed off-label to treat insomnia, particularly tetracyclic antidepressants like mirtazapine. Originally indicated and FDA-approved as an antidepressant, low doses of mirtazapine (7.5–30 mg) have been shown to resolve insomnia symptoms in adults. (13) Care should be taken when administering this drug in elderly patients, particularly males, as it has shown a low clearance rate after oral administration. This drug can be prepared in a variety of concentrations, allowing physicians to easily titrate up the dosage to observe any adverse events.


Amitriptyline is an FDA-approved antidepressant that is also used off-label to treat conditions like anxiety, chronic pain, and insomnia. Low-dose amitriptyline has been shown by patient-reported outcomes to improve the symptoms of insomnia in almost 74 percent of patients in one short-term study. (14) In this study, dry mouth was the most commonly-reported patient-reported side effect, affecting 29 percent of patients. A small subset of patients self-titrated with only 5 mg/day of amitriptyline, but the lowest commercially-available dose is 10 mg tablets. Therefore, some patients may require a compounded preparation to access lower doses.

Why Choose VLS Pharmacy and New Drug Loft?

Sleep aids can be used as either a short-term or long-term therapy to help patients ensure they get quality sleep. Drugs, especially antidepressants, are prescribed off-label and may require compounding to ensure that patients receive an accurate dose, particularly when dose titration is performed. Regardless of which drug is prescribed, our pharmacists will tailor the formulation to meet each individual patient’s specific needs. As a 503A pharmacy specializing in sterile and non-sterile compounding, we will support you and your patients by creating safe, individualized, and effective pharmaceutical therapies. All formulations are compounded with high-quality pharmaceutical-grade APIs sourced directly from PCCA, the leader of superior-quality APIs.


Please comment below with any thoughts or questions.

Reach out to our team to learn about best practices and to partner with our experts on custom compounded medications for your patients. All medications from VLS Pharmacy and New Drug Loft are prepared in a lab that follows safety and quality standards per our status as a 503A pharmacy.



  1. Cote B, Ross B, Fortner J, Rao D. The Use and Utility of Low-dose Naltrexone Capsules for Patients with Fibromyalgia. Int J Pharm Compd. 2018;22(3):252-256.
  2. Bolton MJ, Chapman BP, Van Marwijk H. Low-dose naltrexone as a treatment for chronic fatigue syndrome. BMJ Case Rep. 2020;13(1):e232502. doi:10.1136/bcr-2019-232502
  3. H C, K M, N EF, Dr S, S MG. Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment. Front Immunol. 2021;12. doi:10.3389/fimmu.2021.687806
  4. Jaffer KY, Chang T, Vanle B, et al. Trazodone for Insomnia: A Systematic Review. Innov Clin Neurosci. 2017;14(7-8):24.
  5. Arab A, Rafie N, Amani R, Shirani F. The Role of Magnesium in Sleep Health: a Systematic Review of Available Literature. Biol Trace Elem Res. 2023;201(1):121-128. doi:10.1007/s12011-022-03162-1
  6. Cao Y, Zhen S, Taylor AW, Appleton S, Atlantis E, Shi Z. Magnesium Intake and Sleep Disorder Symptoms: Findings from the Jiangsu Nutrition Study of Chinese Adults at Five-Year Follow-Up. Nutrients. 2018;10(10):1354. doi:10.3390/nu10101354
  7. Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in Anxiety and Sleep: A Large Case Series. Perm J. 2019;23:18-041. doi:10.7812/TPP/18-041
  8. Effects of ramelteon 8 mg on objective sleep latency in adults with chronic insomnia on nights 1 and 2: pooled analysis: Current Medical Research and Opinion: Vol 25, No 5. Accessed June 26, 2023. https://www.tandfonline.com/doi/abs/10.1185/03007990902858527?journalCode=icmo20
  9. Marupuru S, Arku D, Campbell AM, Slack MK, Lee JK. Use of Melatonin and/on Ramelteon for the Treatment of Insomnia in Older Adults: A Systematic Review and Meta-Analysis. J Clin Med. 2022;11(17):5138. doi:10.3390/jcm11175138
  10. Leger D, Quera-Salva MA, Vecchierini MF, Ogrizek P, Perry CA, Dressman MA. Safety profile of tasimelteon, a melatonin MT1 and MT2 receptor agonist: pooled safety analyses from six clinical studies. Expert Opin Drug Saf. 2015;14(11):1673-1685. doi:10.1517/14740338.2015.1093112
  11. Hardeland R. Tasimelteon, a melatonin agonist for the treatment of insomnia and circadian rhythm sleep disorders. Curr Opin Investig Drugs Lond Engl. 2009;10(7):691-701.
  12. Pan Z, Wen S, Qiao X, Yang M, Shen X, Xu L. Different regimens of menopausal hormone therapy for improving sleep quality: a systematic review and meta-analysis. Menopause. 2022;29(5):627-635. doi:10.1097/GME.0000000000001945
  13. Gandotra K, Chen P, Jaskiw GE, Konicki PE, Strohl KP. Effective Treatment of Insomnia With Mirtazapine Attenuates Concomitant Suicidal Ideation. J Clin Sleep Med. 2018;14(5):901-902. doi:10.5664/jcsm.7142
  14. Off‐label low dose amitriptyline for insomnia disorder: Patient‐reported outcomes – Bakker – 2023 – Pharmacoepidemiology and Drug Safety – Wiley Online Library. Accessed February 22, 2024. https://onlinelibrary.wiley.com/doi/full/10.1002/pds.5561




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