Neurim Pharmaceuticals announced publication of the results from an exploratory Phase 2 randomized placebo-controlled clinical trial evaluating the safety and efficacy of add-on Circadin® (Prolonged Release melatonin 2mg) to standard therapy in Alzheimer's disease patients. The study, published in the Clinical Interventions in Aging Journal, demonstrates positive effects of the drug on cognitive performance and sleep maintenance in the Alzheimer's patients.
(DISCLAIMER: Eat2think.com and AlzheimersWeekly.com have no financial interest in Neurim Pharmaceuticals, nor in their melatonin product, Circadin. Their research is reported here due to what it demonstrates about melatonin, a generic supplement. Melatonin is available as a generic supplement in the USA at places like your local pharmacy and Amazon.com.)
Dr. Tali Nir, head of clinical trials at Neurim Pharmaceuticals, said,
"Endogenous melatonin levels are reduced already at preclinical Alzheimer's stages. Because melatonin is important for good sleep quality and because poor sleep quality has recently been linked to Alzheimer's, it was important to investigate whether replenishing the missing hormone would be beneficial in Alzheimer's patients and whether such effects would be related to the improvement in sleep".In this study, 80 patients diagnosed with mild-to-moderate Alzheimer's disease, with and without insomnia co-morbidity, receiving standard therapy (acetylcholinesterase inhibitors with or without memantine) were randomly assigned in a double-blind manner to 2 mg of Circadin® or placebo treatment nightly for 24-weeks. The paper reports that patients treated with Circadin® for 6 months had significantly better cognitive performance than those with placebo as measured by Instrumental Activities of Daily Living (IADL) and Mini Mental State Examination (MMSE). Mean Alzheimer's Disease Assessment Scale - cognition (ADAS-Cog) did not differ between groups. Sleep efficiency as measured by Pittsburgh Sleep Quality Index (PSQI) Component 4 also improved with Circadin®. In a subgroup of patients suffering from comorbid insomnia, Circadin® treatment resulted in significant and clinically meaningful effects vs. placebo in mean IADL (p=0.032), MMSE (+1.5 vs. -3 points, p=0.0177) sleep efficiency (p=0.04), and median ADAS-Cog values (-3.5 vs. +3 points, p=0.045) . The treatment was well tolerated.
Professor Zisapel, CSO of Neurim Pharmaceuticals, said,
"We are very pleased with the encouraging data demonstrating efficacy and safety of add-on Circadin® for 6 months on cognitive functioning and sleep in patients with mild-moderate Alzheimer's. This publication comes at an exciting time when the causal relationship between sleep disturbance and the Alzheimer's-relevant accumulation of beta amyloid in brain was discovered. This study demonstrates the significance of good sleep quality and melatoninergic mechanisms in improving both cognition and sleep problems in Alzheimer patients and calls for further focus of this mechanism in Alzheimer's treatment."
References:
About Circadin:
Circadin® is a novel sleep medication approved by regulatory agencies around the world for the treatment of primary insomnia in patients aged 55 and over. Approval was based on positive effects of Circadin on sleep quality, sleep induction, and daytime functioning without impairing cognitive performance.
About Neurim Pharmaceuticals:
Neurim Pharmaceuticals Ltd. is a neuroscience drug discovery and development pharma company creating drugs for brain restoration & reinforcement. Circadin®-Neurim's first approved drug, is commercially available in over 40 countries. Neurim's advanced-stage pipeline products include prolonged-release melatonin minitabs for pediatric insomnia and Piromelatine for sleep disorders and Alzheimer's Disease.
SOURCE:
Neurim Pharmaceuticals
- Melatonin & Alzheimer's, The Alzheimer's Drug Discovery Foundation
- Clinical Aspects of Melatonin Intervention in Alzheimer’s Disease Progression, Current Neuropharmacology
- The Use of Melatonin in Alzheimer's Disease, Neuro Endocrinology Letters
- Study of Melatonin: Sleep Problems in Alzheimer's Disease, ClinicalTrials.gov
About Circadin:
Circadin® is a novel sleep medication approved by regulatory agencies around the world for the treatment of primary insomnia in patients aged 55 and over. Approval was based on positive effects of Circadin on sleep quality, sleep induction, and daytime functioning without impairing cognitive performance.
About Neurim Pharmaceuticals:
Neurim Pharmaceuticals Ltd. is a neuroscience drug discovery and development pharma company creating drugs for brain restoration & reinforcement. Circadin®-Neurim's first approved drug, is commercially available in over 40 countries. Neurim's advanced-stage pipeline products include prolonged-release melatonin minitabs for pediatric insomnia and Piromelatine for sleep disorders and Alzheimer's Disease.
SOURCE:
Neurim Pharmaceuticals
This study should be evaluated in light of previous studies on using melatonin for Alzheimer's patients ... and possibly in light of the sponsors for each. Two Cochrane meta-analyses have been conducted on available clinical trial data:
ReplyDeletehttp://summaries.cochrane.org/CD009178/medicines-for-sleep-problems-in-alzheimers-disease
This 2014 meta-analysis of three clinical trials for treating insomnia concluded that there was no evidence that melatonin, either immediate- or slow-release, improved any major sleep outcome in patients with Alzheimer's -- not total nocturnal sleep time, the ratio of daytime sleep to night-time sleep, sleep efficiency, time awake after sleep onset, or number of night-time awakenings. One of these studies also evaluated the impact on cognition and performance of activities of daily living (ADLs), and found no difference between treated and control groups.
http://summaries.cochrane.org/CD003802/melatonin-treatment-may-be-effective-for-the-treatment-of-dementia-related-behavior-disturbances
The data from five clinical trials were analyzed for treating dementia-related cognitive, behavioral (excluding sleep), and/or mood disturbances of patients with dementia of any degree of severity. No evidence was found to support the effectiveness of melatonin for the treatment of cognitive impairment. Data from two trials did, however, produce evidence that melatonin may be effective for the treatment of dementia-related psychopathologic behavior disturbances.
Some of the researchers involved in the insomnia trials noted that while melatonin was not found to be beneficial on average, they did not rule out testing it for efficacy on individual patients.
However, they warned that it is not a good idea to give melatonin on a daily basis. Melatonin use on consecutive nights should be avoided, and only the lowest effective dose should be taken. An effective dose is often in the 0.1 - 0.3 mg range.
Repeated administration of doses over 0.3mg can cause the patient to build up a tolerance, and can eventually actually cause insomnia in some people.
Many people believe that since melatonin is "natural", it is also safe. However, melatonin -- like any other treatment that affects the brain -- is not without its risks. In fact, melatonin is a very powerful hormone that affects pretty much every tissue and organ in the body, and the safety of long-term use of oral supplements has NOT been established. (The US is the only "modern" country where a prescription is not required for its use.)
ReplyDeleteMelatonin can cause a number of serious side effects -- including confusion and depression -- which become more likely as the patient continues to receive it. Supplemental melatonin may exacerbate seizure disorders, which is a concern for Alzheimer's patients since they can develop seizure disorders at any stage. Melatonin shrinks arteries and may be contraindicated in persons with cardiovascular disease (including vascular dementia and mixed Alzheimer's and VaD). Melatonin supplementation may aggravate autoimmune disorders such as arthritis and severe allergies. The effects of steroid drugs such as cortisone and dexamethasone may be counteracted by supplemental melatonin. Immune-system cancers such as lymphoma and leukemia may be further stimulated by melatonin supplementation.
Patients with liver or kidney disease (and the elderly, whose liver and/or kidney functions are often compromised) have a decreased melatonin clearance with increased daytime levels of this hormone. They would be more susceptible to problems associated with taking melatonin.
Melatonin can have serious interactions with a number of prescription and nonprescription medications, including "blood thinners" (e.g., warfarin, heparin), blood pressure medications (especially nifedipine), products that contain caffeine (including coffee, tea, some sodas), drugs that may affect the immune system (e.g., azathioprine, cyclosporine, prednisone), fluvoxamine. Tell the doctor or pharmacist if your loved one also takes drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), other medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, amitriptyline, trazodone). Check the labels on all medicines (e.g., cough-and-cold products) because they may contain ingredients that may cause drowsiness.
UPDATE: A newer review was just released that included the studies quoted in Lizzie's comments. It arrived at some important and positive conclusions.
DeleteThe study can be viewed at, "Melatonin for Sleep Disorders and Cognition in Dementia".
The study said that, "We searched all randomized controlled trials published in Medline, Embase, the Cochrane Library, China National Knowledge Infrastructure, the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register, and Clinical Trials.gov...
...there was no report of severe adverse events. Given the current studies, we conclude that melatonin therapy may be effective in improving Sleep Efficacy and prolonging Total Sleep Time in patients with dementia; however, there is no evidence that this improvement impacts cognitive function.