SAVE THE DATE
Laboratory, Endocrine, & Neurotransmitter Symposium
October 4 - 6, 2019
CMES will be available
Gain additional clinical insight and treatment considerations to evaluate some of the most prevalent and challenging conditions that patients present with, including depression, anxiety, altered mental focus and stamina, sexual dysfunction, sleep disturbances, addictions and dependencies, weight management, and chronic disease. Click the button below to be the first to know when registration for LENS 2019 opens.
Topic: Melatonin: An Introduction
By: Krista Anderson Ross, ND
May 1, 2019
Join our clinical staff and special guests on the first Wednesday of every month at 9:30 AM and 12:00 PM PST. This free, live webinar series will cover a variety of neuroendocrine topics that will enhance your knowledge, with clinically applicable testing and treatment considerations. 1 CE credit available upon attendee request.
Phoenix, AZ: April 24-28, 2019
Make sure to visit the our booth at AAEM in Phoenix later this month. Chat with our representative to learn what's new!
Portland, OR: April 26-28, 2019
Come visit our booth at the IWHIM conference in Portland, OR, this month.
Melatonin as a Potential Therapy for Traumatic Brain Injury (TBI)
By Krista Anderson-Ross, ND | April 16, 2019
You might be surprised to learn that traffic accidents are the third leading cause of traumatic brain injury (TBI) in the US, accounting for only 14% of total TBI’s. Blows to the head account for 15%, and falls cause the majority of TBI’s at 47%. The CDC defines a TBI as “a bump, blow or jolt to the head or a penetrating head injury that disrupts the normal function of the brain.” The resulting primary damage may include shearing/tearing injuries of white matter, focal contusions, hematomas, or cerebral edema. Soon after the primary damage a cascade of metabolic events sets in which can cause secondary brain damage, which may result from the generation of free radicals, release of neurotransmitters, inflammatory responses, calcium-mediated damage, mitochondrial dysfunction, and gene activation.
TBI’s are on the rise; from 2006 to 2014 the number of TBI related emergency department visits, hospitalizations and deaths increased by 53%. Currently there are no FDA-approved therapies for TBI, which translates into many suffering long-term disabilities associated with this injury.
Because melatonin possesses the ability to cross the blood-brain barrier, has receptors in the CNS, and is low in toxicity, it is being explored as a promising potential TBI therapeutic. A recent literature review (May 2018) explored published research on the use of melatonin after TBI. The majority of studies reviewed were animal studies and a few were human-based. There was a trend among both human and animal studies for melatonin levels to initially increase after TBI up to day 2-3, after which point melatonin levels decreased below pre-injury levels and remained depressed chronically (the longest reported research collected data for only three weeks). The authors suggest that what seems to be an acute increase of melatonin immediately post-injury is inadequate for neuroprotection as a result of the chronically low levels of melatonin that persist thereafter. Given the trend of post-concussive chronically low melatonin levels, it’s not surprising that 30-70% of TBI patients report sleep complaints including insomnia, hypersomnolescence (excessive daytime sleepiness), and altered sleep-wake cycles.
Sleep disturbances are some of the most disabling consequences of TBI and may contribute to other symptoms associated with TBI including pain; depression and anxiety; poor memory, attention and executive functioning, and impaired social functioning. This population of TBI sufferers have longer hospital stays and once discharged are at an increased risk for suicide.
While the therapeutic effects of melatonin in human TBIs are understudied, melatonin has demonstrated beneficial effects in pre-clinical models of several CNS disorders with similar pathology and symptoms to TBI such as Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), stroke, sepsis-induced brain dysfunction, and spinal cord injury. Melatonin has been shown to reduce the effects of secondary injury in these conditions caused by apoptosis, inflammation and oxidative stress, and has been shown to reduce the associated functional deficits in the areas of memory, learning, and motor control.
There is an ongoing trial in Canada called the PLAYGAME study exploring the effects of therapeutic melatonin after pediatric TBI. In its initial stages, a retrospective chart review of 48 children being treated for TBI post-traumatic headache revealed that melatonin was in use as a treatment modality in 37.5% of the charts, suggesting that melatonin is already being administered for TBI in some clinical settings. More children responded to treatment with melatonin (83%) when compared with the other treatments used, and no serious side effects were reported. This research is ongoing and results are forthcoming.
The researchers of the literature review concluded that the published evidence “suggests that melatonin is a safe and low toxic drug with neuroprotective properties after TBI.” Currently most evidence is based on data from adult male rats; more human studies are indicated. While practitioners often utilize neurotransmitter testing in these patients, providers should also consider melatonin testing for TBI patients, even if the injury took place months or even years prior to presenting to the clinic. Balancing neurotransmitters and considering melatonin therapy could offer beneficial effects for TBI sufferers who don’t have many therapeutic interventions from which to choose.
Osier N, McGreevy E, Pham L, et al. Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence. Int J Mol Sci. 2018;19(5):1539. Published 2018 May 22. doi:10.3390/ijms19051539
Shekleton JA, Parcell DL, Redman JR, Phipps-Nelson J, Ponsford JL, Rajaratnam SM. Sleep disturbance and melatonin levels following traumatic brain injury. Neurology. 2010;74(21):1732–1738. doi:10.1212/WNL.0b013e3181e0438b
Barlow KM, Brooks BL, MacMaster FP, et al. A double-blind, placebo-controlled intervention trial of 3 and 10 mg sublingual melatonin for post-concussion syndrome in youths (PLAYGAME): study protocol for a randomized controlled trial. Trials. 2014;15:271. Published 2014 Jul 7. doi:10.1186/1745-6215-15-271
Rao, V, Neubauer, D, Vaishnavi, S. Sleep Disturbances After Traumatic Brain Injury. Psychiatric Times. 2015; 32 (9). https://www.psychiatrictimes.com/special-reports/sleep-disturbances-after-traumatic-brain-injury/page/0/1