Author: Alex Thompson

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

The sleep disturbances exacerbate cognitive performance deficits and behavioural problems and subsequently entire family distress (Doo and Wing, 2006). The use of melatonin for treating chronic sleep–wake cycle disorders of children with ASD/NGD is increasing (Rossignol and Frye, 2011; Cortesi et al.,2012; Gringras et al.,2012; 2017; Malow et al.,2012; Cuomo et al.,2017). Melatonin‐based therapy, if approved by the health authorities, could become a standard treatment of insomnia in neurodevelopmentally‐challenged children. Melatonin and melatonergic drugs showed beneficial effects not only in the treatment of insomnia but also in various related conditions such as parasomnia, circadian rhythm disorders, night eating disorders, and depression. The newly developed melatonin and melatonergic drugs have the potential to be used extensively in various clinical situations.

Explore Sleep Foundation

Disturbances of the circadian sleep–wake cycle represent one of the core features of delirium, leading to the hypothesis that the neurotransmitter melatonin and changes in its metabolism may be involved in the pathogenesis of delirium. Therefore, attention has focused upon the possible role of the circadian timing system in the pathophysiology of delirium (26). Melatonin at 2 mg PR may be useful during benzodiazepine or hypnotics discontinuation and may improve self-reported sleep quality during benzodiazepine withdrawal (15, 47). It is often safe for healthy adults to take natural sleep aids and other dietary supplements; however, because many of these products have not been extensively tested, their effects may be unpredictable.

Valerian Root for Sleep

The prevalence rate of insomnia in the Korean adult population has been estimated to range from 10% to 30% and is similar to the rate reported in adults in Western countries 2. The consequences of sleep disorders are irritability, daytime sleepiness, low energy and motivation, physical discomfort, and impaired cognitive functioning 3,4. Sleep disorders lead to a significant burden on the healthcare system in Korea.

The positive effects of melatonin seemed to be maintained in the long term (58). Another randomized controlled trial was conducted on 60 children with ADHD with or without insomnia, treated with IR and methylphenidate. The administration of 3–6 mg melatonin was related to an improvement in sleep onset latency and total time of sleep, but with no effect on the intensity of inattention or hyperactivity symptoms (59).

  1. In particular, an improvement of about 30 min in sleep onset latency and of about 20 min of total sleeping time an advance in the endogenous secretion of melatonin by 44 min was observed (57).
  2. These sleep aids should not be combined with other sedatives, like alcohol, opiates, or benzodiazepines.
  3. In the subgroup analysis of patients with severe depression, agomelatine showed better outcomes that were statistically significant.
  4. Whether melatonin add‐on therapy can improve cardiovascular outcome with ageing remains to be further explored.

MELATONIN AGONIST: RAMELTEON

Since it is mainly metabolized in the liver, caution should be exercised during the administration of agomelatine to patients with liver disease. The area under the concentration-time curve for a single 16 mg dose was 31% higher, whereas the maximal concentration was 22% lower than when ramelteon was administered in a fasted state 25. Therefore, the US FDA does not recommend administering ramelteon after a high-fat meal. While it can cause some similar side effects, the risk is generally lower than with other prescription sleep medications.

Orexin Receptor Antagonists

Treatment of irregular rhythms or delayed sleep phase should follow previous indications by using IR melatonin ≤ 1 mg (4, 8). Delirium is a transient change to attention and cognition that develops over a short period, is fluctuating in nature, and commonly involves disruption of the sleep–wake cycle (67). It is a common condition affecting at least 10% of older patients at the time of admission to hospital and between 14 and 56% during hospitalization for a review (26). Some antipsychotics have a sedative effect, but none have been approved by the FDA or recommended by AASM for treating sleeping problems.

Side Effects of Sleep Medication

One demonstrated improved efficiency17 while one reported worsened sleep efficiency18. However, the worsened sleep efficiency (and accompanying prolonged REM sleep latency and increased duration of wakefulness) was a comparison between sleep parameters on the first night to the second night of the study. The study objective was to investigate the impact of melatonin on ‘the first night effect (FNE)’, whereby individuals have a tendency to experience poorer sleep quality on the first night of a sleep evaluation study18. Therefore, while this study demonstrated that melatonin does not ameliorate the FNE, conclusions cannot be drawn about extended sleep efficiency.

Considering the role of sleep in memory consolidation, it is not surprising that insufficient sleep can reduce cognitive ability including attention and memory. These symptoms are of particular concern in older subjects, because they may be misinterpreted as symptoms of dementia/mild cognitive impairment (MCI) (Roth and Ancoli‐Israel, 1999). There is a strong association of objectively and subjectively measured sleep quality with subsequent cognitive decline (Osorio et al.,2011; Blackwell et al.,2014). A common side effect of antipsychotic medications used to treat schizophrenia is a condition called tardive dyskinesia, which causes involuntary movements. In a study of 22 people with schizophrenia and tardive dyskinesia caused by antipsychotic medications, those who took melatonin supplements had fewer symptoms compared to those who did not take the supplements.

Based on this search, 60 articles were identified, with 35 articles being selected according to the inclusion/exclusion criteria, including most recent meta-analyses and systematic reviews. Thirteen articles were considered for mood disorders, 1 for ADHD in adults, 1 for ASD in adults, 5 for delirium, 7 for neurocognitive disorders, 6 for schizophrenia, 2 for substance use disorders, and no studies for anxiety and eating disorders (Figure 1). The resulting recommendations by the international expert task force regarding potential indications of melatonin for insomnia and circadian rhythm disorders in adult with psychiatric disorders are summarized after each disorder taken into consideration. Two publications reported different sleep outcomes from the same study whose primary aim was to observe the effect of melatonin on BZD discontinuation/reduction in patients with a diagnosis of schizophrenia or bipolar disorder.