What is Ramelteon?


Ramelteon, sold under the brand name Rozerem among others, is a sleep agent medication that selectively binds to the MT1 and MT2 receptors in the suprachiasmatic nucleus (SCN), instead of binding to GABAA receptors, such as with drugs like zolpidem.

It appears to speed the onset of sleep and alter the total amount of sleep a person gets. It is approved by the US Food and Drug Administration (FDA) for long-term use.

Ramelteon does not show any appreciable binding to GABAA receptors, which are associated with anxiolytic, myorelaxant, and amnesic effects.

Brief History

Ramelteon was approved for use in the United States in July 2005.

Medical Uses

Ramelteon is approved in the United States for the treatment of insomnia characterised by difficulty with sleep onset.

A systematic review, published in 2014, concluded “ramelteon was found to be beneficial in preventing delirium in medically ill individuals when compared to placebo.”

Mechanism of Action

Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and selectivity over the MT3 receptor. Ramelteon demonstrates full agonist activity in vitro in cells expressing human MT1 or MT2 receptors, and high selectivity for human MT1 and MT2 receptors compared to the MT3 receptor.

The activity of ramelteon at the MT1 and MT2 receptors is believed to contribute to its sleep-promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle. Ramelteon has no appreciable affinity for the GABA receptor complex or for receptors that bind neuropeptides, cytokines, serotonin, dopamine, noradrenaline, acetylcholine, and opioids. Ramelteon also does not interfere with the activity of a number of selected enzymes in a standard panel.

The major metabolite of ramelteon, M-II, is active and has approximately one tenth and one fifth the binding affinity of the parent molecule for the human MT1 and MT2 receptors, respectively, and is 17-25-fold less potent than ramelteon in in vitro functional assays. Although the potency of M-II at MT1 and MT2 receptors is lower than the parent drug, M-II circulates at higher concentrations than the parent producing 20-100-fold greater mean systemic exposure when compared to ramelteon. M-II has weak affinity for the serotonin 5-HT2B receptor, but no appreciable affinity for other receptors or enzymes. Similar to ramelteon, M-II does not interfere with the activity of a number of endogenous enzymes.

Adverse Effects

Ramelteon has not been shown to produce dependence and has shown no potential for abuse, and the withdrawal and rebound insomnia that is typical with GABA modulators is not present in ramelteon.

Six percent of ramelteon-treated patients in clinical trials discontinued due to an adverse event, compared with two percent in the placebo arms. The most frequent adverse events leading to discontinuation were somnolence, dizziness, nausea, fatigue, headache, and insomnia. The US official Prescribing Information warns of rare cases of anaphylactic reactions, abnormal thinking, worsening of depression or suicidal thinking in patients with pre-existing depression, and decreased testosterone and increased prolactin levels. It also notes that ramelteon is not recommended for use in patients with severe sleep apnoea.

In mice treated with ramelteon for two years, increases in liver and testicular tumours were observed, but only at doses at least 20 times greater than the recommended human dose on a milligram/kilogram basis.

Drug Interactions

Ramelteon has been evaluated for potential drug interactions with the following medications and showed no significant effects: omeprazole, theophylline, dextromethorphan, and midazolam, digoxin and warfarin. There were no clinically meaningful effects when ramelteon was co-administered with any of these drugs.

A drug interaction study showed that there were no clinically meaningful effects or an increase in adverse events when ramelteon and the SSRI Prozac (fluoxetine) were co-administered. When co-administered with ramelteon, fluvoxamine (strong CYP1A2 inhibitor) increased AUC approximately 190-fold, and the Cmax increased approximately 70-fold, compared to ramelteon administered alone. Ramelteon and fluvoxamine should not be co-administered.

Ramelteon has significant drug-drug interaction with the following drugs: amiodarone, ciprofloxacin, fluvoxamine, ticlopidine.

Ramelteon should be administered with caution in patients taking other CYP1A2 inhibitors, strong CYP3A4 inhibitors such as ketoconazole, and strong CYP2C9 inhibitors such as fluconazole.

Efficacy may be reduced when ramelteon is used in combination with potent CYP enzyme inducers such as rifampin, since ramelteon concentrations may be decreased.

What is Parasomnia?


Parasomnias are a category of sleep disorders that involve abnormal movements, behaviours, emotions, perceptions, and dreams that occur while falling asleep, sleeping, between sleep stages, or during arousal from sleep.

Parasomnias are dissociated sleep states which are partial arousals during the transitions between wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, and their combinations.

Refer to Night Eating Syndrome (NES) and Sleep-Related Eating Disorder (SRED).


The International Classification of Sleep Disorders (ICSD uses State Dissociation as the paradigm for parasomnias. Unlike before, where wakefulness, NREM sleep, and REM sleep were considered exclusive states, research has shown that combinations of these states are possible and thus, may result in unusual unstable states that could eventually manifest as parasomnias or as altered levels of awareness.

Although, the previous definition is technically correct, it contains flaws. The consideration of the State Dissociation paradigm facilitates the understanding of the sleep disorder and provides a classification of 10 core categories.

NREM-Related Parasomnias

NREM parasomnias are arousal disorders that occur during stage 3 (or 4 by the R&K standardisation) of NREM sleep – also known as slow wave sleep (SWS). They are caused by a physiological activation in which the patient’s brain exits from SWS and is caught in between a sleeping and waking state. In particular, these disorders involve activation of the autonomic nervous system, motor system, or cognitive processes during sleep or sleep-wake transitions.

Some NREM parasomnias (sleep-walking, night-terrors, and confusional arousal) are common during childhood but decrease in frequency with increasing age. They can be triggered in certain individuals, by alcohol, sleep deprivation, physical activity, emotional stress, depression, medications, or a fevered illness. These disorders of arousal can range from confusional arousals, somnambulism, to night terrors. Other specific disorders include sleepeating, sleep sex, teeth grinding, rhythmic movement disorder, restless legs syndrome, and somniloquy.

Differential Diagnosis for NREM-Related Parasomnias

  • Sleep-disordered breathing.
  • REM-related parasomnias.
  • Nocturnal seizures.
  • Psychogenic dissociative disorders

Confusional Arousals

Confusional arousal is a condition when an individual awakens from sleep and remains in a confused state. It is characterized by the individual’s partial awakening and sitting up to look around. They usually remain in bed and then return to sleep. These episodes last anywhere from seconds to minutes and may not be reactive to stimuli. Confusional arousal is more common in children than in adults. It has a lifetime prevalence of 18.5% in children and a lifetime prevalence of 2.9-4.2% in adults. Infants and toddlers usually experience confusional arousals beginning with large amounts of movement and moaning, which can later progress to occasional thrashings or inconsolable crying. In rare cases, confusional arousals can cause injuries and drowsy driving accidents, thus it can also be considered dangerous. Another sleeping disorder may be present triggering these incomplete arousals.

Sleep-Related Abnormal Sexual Behaviour

Sleep-related abnormal sexual behaviour, Sleep sex, or sexsomnia, is a form of confusional arousal that may overlap with somnambulism. Thereby, a person will engage in sexual acts while still asleep. It can include such acts as masturbation, inappropriate fondling themselves or others, having sex with another person; and in more extreme cases, sexual assault. These behaviours are unconscious, occur frequently without dreaming, and bring along clinical, social, and legal implications. It has a lifetime prevalence of 7.1% and an annual prevalence of 2.7%.

Sleepwalking (Somnambulism)

Sleepwalking has a prevalence of 1-17% in childhood, with the most frequent occurrences around the age of eleven to twelve. About 4% of adults experience somnambulism. Normal sleep cycles include states varying from drowsiness all the way to deep sleep. Every time an individual sleeps, he or she goes through various sequences of non-REM and REM sleep. Anxiety and fatigue are often connected with sleepwalking. For adults, alcohol, sedatives, medications, medical conditions and mental disorders are all associated with sleepwalking. Sleep walking may involve sitting up and looking awake when the individual is actually asleep, and getting up and walking around, moving items or undressing themselves. They will also be confused when waking up or opening their eyes during sleep. Sleep walking can be associated with sleeptalking.

Sleep Terrors (Night Terrors/Pavor Nocturnus)

Sleep terror is the most disruptive arousal disorder since it may involve loud screams and panic; in extreme cases, it may result in bodily harm or property damage by running about or hitting walls. All attempts to console the individual are futile and may prolong or intensify the victim’s confused state. Usually the victim experiences amnesia after the event but it may not be complete amnesia. Up to 3% of adults suffer from sleep terrors and exhibited behaviour of this parasomnia can range from mild to extremely violent. This is very prevalent in those who suffer violent post-traumatic stress disorder (PTSD). They typically occur in stage 3 sleep.

Sleep-Related Eating Disorder (SRED)

The Diagnostic and Statistical Manual of Mental Disorders (DSM) classifies sleep-related eating disorder (SRED) under sleepwalking, while ICSD classifies it as NREM-related parasomnia. It is conceptualised as a mixture of binge-eating behaviour and arousal disorder. Thereby, preferentially high-caloric food is consumed in an uncontrolled manner. However, SRED should not be confused with nocturnal eating syndrome, which is characterised by an excessive consumption of food before or during sleep in full consciousness. Since sleep-related eating disorders are associated with other sleep disorders, successful treatment of the latter can reduce symptoms of this parasomnia.

REM-Related Parasomnias

REM Sleep Behaviour Disorder

Unlike other parasomnias, rapid eye movement sleep behaviour disorder (RBD) in which muscle atonia is absent is most common in older adults. This allows the individual to act out their dreams and may result in repeated injury – bruises, lacerations, and fractures – to themselves or others. Patients may take self-protection measures by tethering themselves to bed, using pillow barricades, or sleeping in an empty room on a mattress. Besides ensuring the sleep environment is a safe place, pharmacologic therapy using melatonin and clonazepam is also common as a treatment for RBD, even though might not eliminate all abnormal behaviours. Before starting a treatment with clonazepam, a screening for obstructive sleep apnoea should performed. However, clonazepam needs to be manipulated carefully because of its significant side effects, i.e. morning confusion or memory impairment, mainly in patients with neurodegenerative disorders with dementia.

Demographically, 90% of RBD patients are males, and most are older than 50 years of age. However, this prevalence in males could be biased due to the fact that women tends to have a less violent type of RBD, which leads to lower reports at sleep centres and different clinical characteristics. While men might have more aggressive behaviour during dreaming, women have presented more disturbance in their sleep. RBD may be also influenced by a genetic compound, since primary relatives seem to have significantly more chance to develop RBD compared with non-relatives control group.

Typical clinical features of REM sleep behavior disorder are:

  • Male gender predilection.
  • Mean age of onset 50-65 years (range 20-80 years).
  • Vocalisation, screaming, swearing that may be associated with dreams.
  • Motor activity, simple or complex, that may result in injury to patient or bed-partner.
  • Occurrence usually in latter half of sleep period (REM sleep).
  • May be associated with neurodegenerative disease.

Acute RBD occurs mostly as a result of a side-effect in prescribed medication – usually antidepressants. Furthermore, substance abuse or withdrawal can result in RBD.

Chronic RBD is idiopathic, meaning of unknown origin, or associated with neurological disorders. There is a growing association of chronic RBD with neurodegenerative disorders – Parkinson’s disease, multiple system atrophy (MSA), or dementia – as an early indicator of these conditions by as much as 10 years. RBD associated with neurological disorders is frequently related to abnormal accumulation of alpha-synuclein, and more than 80% of patients with idiopathic RBD might develop Lewy body disease (LBD). Patients with narcolepsy are also more likely to develop RBD.

The diagnosis is based on clinical history, including partner’s account and needs to be confirmed by polysomnography (PSG), mainly for its accuracy in differentiating RBD from other sleep disorders, since there is a loss of REM atonia with excessive muscle tone. However, screening questionnaires, such as the REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ), are also very useful for diagnosing RBD.

Recurrent Isolated Sleep Paralysis

Recurrent isolated sleep paralysis is an inability to perform voluntary movements at sleep onset, or upon waking from sleep. Although the affected individual is conscious and recall is present, the person is not able to speak or move. However, respiration remains unimpaired. The episodes last seconds to minutes and diminish spontaneously. The lifetime prevalence is 7%. Sleep paralysis is associated with sleep-related hallucinations. Predisposing factors for the development of recurrent isolated sleep paralysis are sleep deprivation, an irregular sleep-wake cycle, e.g. caused by shift work, or stress. A possible cause could be the prolongation of REM sleep muscle atonia upon awakening.

Nightmare Disorder

Nightmares are like dreams primarily associated with REM sleep. Nightmare disorder is defined as recurrent nightmares associated with awakening dysphoria that impairs sleep or daytime functioning. It is rare in children, however persists until adulthood. About two thirds of the adult population report experiencing nightmares at least once in their life.


Before the ICSD-3, Catathrenia was classified as a rapid-eye-movement sleep parasomnia, but is now classified as sleep-related breathing disorder. It consists of breath holding and expiratory groaning during sleep, is distinct from both somniloquy and obstructive sleep apnoea. The sound is produced during exhalation as opposed to snoring which occurs during inhalation. It is usually not noticed by the person producing the sound but can be extremely disturbing to sleep partners, although once aware of it, sufferers tend to be woken up by their own groaning as well. Bed partners generally report hearing the person take a deep breath, hold it, then slowly exhale; often with a high-pitched squeak or groaning sound.

Sleep-Related Painful Erections

Painful erections appear only during the sleep. This condition is present during the REM sleep. Sexual activity doesn’t produce any pain. There is not any lesion or physical damage but an hypertonia of the pelvic floor could be one cause. It affects men of all ages but especially from the middle-age. Some pharmacologic treatment as propranolol, clozapine, clonazepam, baclofen and various antidepressants, seems to be effective.

Other Parasomnias

Exploding head syndrome

Exploding head syndrome (EHS) is an abnormal sensory perception during sleep in which a person experiences unreal noises that are loud and of short duration when falling asleep or waking up. The noise may be frightening, typically occurs only occasionally, and is not a serious health concern. People may also experience a flash of light. Pain is typically absent.

Despite the name, the sufferer’s head does not actually explode!

Sleep-Related Hallucinations

Sleep-related hallucinations are brief episodes of dream-like imagery that can be of any sensory modality, i.e. auditory, visual, or tactile. They are differentiated between hypnagogic hallucination, that occur at sleep onset, and hypnopompic hallucinations, which occur at the transition of sleep to awakening. Although normal individuals have reported nocturnal hallucinations, they are more frequent in comorbidity with other sleep disorders, e.g. narcolepsy.

Sleep Enuresis

Nocturnal enuresis, also called bedwetting, is involuntary urination while asleep after the age at which bladder control usually begins. Bedwetting in children and adults can result in emotional stress. Complications can include urinary tract infections.

Parasomnias Due to Medical Disorder

Parasomnias Due to Medication or Substance

Parasomnia (Unspecific)

Sleep drunkenness, also known as confusional arousal, is the feeling of confusion or sudden action upon waking up from deep sleep. Severe sleep inertia, one cause of oversleeping, is considered to develop sleep drunkenness.

Isolated Symptom/Normal Variant

Sleep Talking (Somniloquy)

According to ICSD-3 it is not defined a disorder in particular. It is rather an isolated symptom or normal variant and ranges from isolated speech to full conversations without recall. With a lifetime prevalence of 69% it is considered fairly common. Sleep talking is associated with REM-related parasomnias as well as with disorders or arousal. It occurs in all sleep states. As yet, there is no specific treatment for sleeptalking available.


Parasomnias are most commonly diagnosed by means of questionnaires. These questionnaires include a detailed analyses of the clinical history and contain questions to:

  • Rule out sleep deprivation.
  • Rule out effects of intoxication or withdrawal.
  • Rule out sleep disorders causing sleep instability.
  • Rule out medical disorders or treatments associated with sleep instability.
  • Confirm presence of NREM parasomnias in other family members and during the patient’s childhood.
  • Determine the timing of the events.
  • Determine the morphology of the events.

Furthermore, a sleep diary is helpful to exclude that sleep deprivation could be a precipitating factor. An additional tool could be the partner’s log of the events. The following questions should therefore be considered:

  • Do you or your bed partner believe that you move your arms, legs, or body too much, or have unusual behaviours during sleep?
  • Do you move while dreaming, as if you are simultaneously attempting to carry out the dream? l Have you ever hurt yourself or your bed partner during sleep?
  • Do you sleepwalk or have sleep terrors with loud screaming?
  • Do your legs feel restless or begin to twitch a lot or jump around when you are drowsy or sleepy, either at bedtime or during the day?
  • Do you eat food or drink fluids without full awareness during the night? Do you wake up in the morning feeling bloated and with no desire to eat breakfast?

In potentially harmful or disturbing cases a specialist in sleep disorders should be approached. Video polysomnographic documentation is necessary only in REM sleep behaviour disorder (RBD), since it is an essential diagnostic criteria in the ICSD to demonstrate the absence of muscle atonia and to exclude comorbid sleep disorders. For most of the other parasomnias, polysomnographic monitoring is a costly, but still supportive tool in the clinical diagnosis.

The use of actigraphy can be promising in the diagnostical assessment of NREM-related parasomnias, for example to rule out sleep deprivation or other sleep disorders, like circadian sleep-wake rhythm disorder which often develops among shift workers. However, there is currently no generally accepted standardised technique available of identifying and quantifying periodic limb movements in sleep (PLMS) that distinguishes movements resulting from parasomnias, nocturnal seizures, and other dyskinesias. Eventually, using actigraphy for parasomnias in general is disputed.


Parasomnias can be considered as potentially harmful to oneself as well as to bed partners, and are associated with other disorders. Children with parasomnias do not undergo medical intervention, because they tend to recover the NREM-related disorder with the process of growth. In those cases, the parents receive education on sleep hygiene to reduce and eventually eliminate precipitating factors.

In adults psychoeducation about a proper sleep hygiene can reduce the risk to develop parasomnia. Case studies have shown that pharmacological interventions can improve symptoms of parasomnia, however mostly they are accompanied by side-effects. Behavioural treatments, i.e. relaxation therapy, biofeedback, hypnosis, and stress reduction, may also be helpful, but are not considered as universally effective.


NREM-related parasomnias which are common in childhood show a good prognosis, since severity decreases with age, the symptoms tend to resolve during puberty. Adults suffering from NREM-related parasomnias, however, are faced with a stronger persistence of the symptoms, therefore, full remission is quite unlikely and is also associated with violent complications, including homicide. The variant sleep-related eating disorders is chronic, without remission, but treatable.

REM sleep behaviour disorder (RBD) can mostly be handled well with the use of melatonin or clonazepam. However, there is high comorbidity with neurodegenerative disorders, that is in up to 93% of cases. The underlying psychopathology of nightmare disorder complicates a clear prognosis.

The prognosis for other parasomnias seems promising. While exploding head syndrome usually resolves spontaneously, the symptoms for sleep-related hallucinations tend to diminish over time.

What is Sleep-Related Eating Disorder?


Nocturnal sleep-related eating disorder (SRED) is a combination of a parasomnia and an eating disorder.

It is a non-rapid eye movement (NREM) parasomnia. It is described as being in a specific category within somnambulism or a state of sleepwalking that includes behaviours connected to a person’s conscious wishes or wants. Thus many times SRED is a person’s fulfilling of their conscious wants that they suppress; however, this disorder is difficult to distinguish from other similar types of disorders.

Comparison with Night Eating Syndrome

SRED is closely related to night eating syndrome (NES) except for the fact that those suffering from NES are completely awake and aware of their eating and bingeing at night while those suffering from NSRED are sleeping and unaware of what they are doing.

NES is primarily considered an eating disorder while SRED is primarily considered a parasomnia; however, both are a combination of parasomnia and eating disorders since those suffering from NES usually have insomnia or difficulty sleeping and those suffering from SRED experience symptoms similar to binge eating. Some even argue over whether NES and SRED are the same or distinct disorders.

Even though there have been debates over these two disorders, specialists have examined them to try to determine the differences. Dr. J. Winkelman noted several features of the two disorders that were similar, but he gave one important factor that make these disorders different. In his article “Sleep-Related Eating Disorder and Night Eating Syndrome: Sleep Disorders, Eating Disorders, Or both”, Winkelman said, “Both [disorders] involve nearly nightly binging at multiple nocturnal awakenings, defined as excess calorie intake or loss of control over consumption.” He also reported that both disorders have a common occurrence of approximately one to five percent of adults, have been predominantly found in women, with a young adult onset, have a chronic course, have a primary morbidity of weight gain, sleep disruption, and shame over loss of control over food intake, have familial bases, and have been observed to have comorbid depression and daytime eating disorders. However, Winkelman said, “The most prominent cited distinction between NES and SRED is the level of consciousness during nighttime eating episodes.” Therefore, these two disorders are extremely similar with only one distinction between them.

Medical professionals and psychologists have difficulty differentiating between NES and SRED, but the distinction of a person’s level of consciousness is what doctors chiefly rely on to make a diagnosis. One mistake that is often made is the misdiagnosis of SRED for NES. However, even though SRED is not a commonly known and diagnosed disease, many people suffer from it in differing ways while doctors work to find a treatment that works for everyone; several studies have been done on SRED, such as the one conducted by Schenck and Mahowald. These studies, in turn, provide the basic information on this disorder including the symptoms, behaviours, and possible treatments that medical professionals are using today.

Brief History

The first case of SRED was reported in 1955, but over the next 36 years, only nine more reports were made of this syndrome. Seven of these reports were single-case studies and the other two instances were seen during objective sleep studies, all done by psychiatrists and doctors.

Schenck and Mahowald were the first to a major study on this disorder. They started their study of NSRED in 1985 and continued until 1993 with several cases among a total of 38 other various sleep-related disorders. Many of the cases they observed had symptoms that overlapped with those of NES, but this study was the first to discover that SRED was different from NES in the fact that those suffering from SRED were either partially or completely unaware of their actions at night while those with NES were aware. Schenck and Mahowald also discovered that none of the patients had any eating instability before their problems at night while sleeping. In their 1993 report, they summarised the major findings with the idea that women encompass at least two thirds of the patients and that the majority of these patients had become overweight. They also discovered that while the patients’ night-eating normally started during early adulthood, this wasn’t always the case as it started as early as childhood to as late as middle adulthood. These patients not only had SRED, but many of them had also been suffering from other night time behaviours such as sleep terrors for several years. This revolutionised the way people saw SRED.

With the technological age growing and more people becoming obese, Schenck and Mahowald’s discovery of SRED causing a large weight increase helped medical professionals more easily identify this disorder – almost half of Schenck and Mahowald’s patients were significantly obese. According to body mass index’s criteria, no patient was emaciated. Schenck and Mahowald said, “virtually all patients had accurate non-distorted appraisals of their body size, shape, and weight. Furthermore, unlike the patients in Stunkard’s series, none of our patients had problematic eating in the evening between dinner and bedtime; sleep onset insomnia was not present; and sleep latency was usually brief, apart from several patients with RLS.” After realising what was wrong with them, many of Schenck and Mahowald’s patients with SRED restricted their day eating and over exercised.

Signs and Symptoms

Over the past 30 years, several studies have found that those afflicted with SRED all have different symptoms and behaviours specific to them, yet they also all have similar characteristics that medical professionals and psychologists have identified to distinguish SRED from other combinations of sleep and eating disorders such as night eating syndrome. Winkelman says that typical behaviours for patients with SRED include: “Partial arousals from sleep, usually within 2 to 3 hours of sleep onset, and subsequent ingestion of food in a rapid or ‘out of control’ manner.” They also will attempt to eat bizarre amalgamations of foods and even potentially harmful substances such as glue, wood, or other toxic materials. In addition, Schenck and Mahowald noted that their patients mainly ate sweets, pastas, both hot and cold meals, improper substances such as “raw, frozen, or spoiled foods; salt or sugar sandwiches; buttered cigarettes; and odd mixtures prepared in a blender.”

During the handling of this food, patients with SRED distinguish themselves, as they are usually messy or harmful to themselves. Some eat their food with their bare hands while others attempt to eat it with utensils. This occasionally results in injuries to the person as well as other injuries. After completing their studies, Schenck and Mahowald said, “Injuries resulted from the careless cutting of food or opening of cans; consumption of scalding fluids (coffee) or solids (hot oatmeal); and frenzied running into walls, kitchen counters, and furniture.” A few of the more notable symptoms of this disorder include large amounts of weight gain over short periods of time, particularly in women; irritability during the day, due to lack of restful sleep; and vivid dreams at night. It is easily distinguished from regular sleepwalking by the typical behavioural sequence consisting of “rapid, ‘automatic’ arising from bed, and immediate entry into the kitchen.” In addition, throughout all of the studies done, doctors and psychiatrists discovered that these symptoms are invariant across weekdays, weekends, and vacations as well as the eating excursions being erratically spread throughout a sleep cycle.

Most people that suffer from this disease retain no control over when they arise and consume food in their sleep. Although some have been able to restrain themselves from indulging in their unconscious appetites, some have not and must turn to alternative methods of stopping this disorder. It is important for trained physicians to recognise these symptoms in their patients as quickly as possible, so those with SRED may be treated before they injure themselves.


The diagnostic criteria utilised by the International Classification of Sleep Disorders – Third Edition (ICSD-3) include some dysfunctional eating when the person wake up during the main sleep period, eating unusual or toxic food, negative health consequences. The patient could be injured during these episodes and he might not be conscious and will not remember them. This criterion differentiates SRED from NES. Patients with NES are conscious during the episode.


For those patients who have not been able to stop this disorder on their own, medical professionals have been working to discover a treatment that will work for everyone. One treatment that Schenck and Mahowald studied consisted of psychotherapy combined with “environmental manipulation”. This was usually done separately from the weight-reducing diets. However, during this study only 10% of the patients were able to lose more than one third of their initial excess weight, which was not a viable percentage. In addition, they reported that many of the patients experienced “major depression” and “severe anxiety” during the attempted treatments. This was not one of the most successful attempts to help those with SRED.

However, Dr. R. Auger reported on another trial treatment where patients were treated utilising pramipexole. Those conducting the treatment noticed how the nocturnal median motor activity was decreased, as was assessed by actigraphy, and individual progress of sleep quality was reported. Nevertheless, Augur also said, “27 percent of subjects had RLS (restless legs syndrome, a condition known to respond to this medication), and number and duration of waking episodes related to eating behaviours were unchanged.” Encouraged by the positive response verified in the above-mentioned trial treatment, doctors and psychiatrists conducted a more recent study described by Auger as “efficacy of topiramate [an antiepileptic drug associated with weight loss] in 17 consecutive patients with NSRED.” Out of the 65% of patients who continued to take the medication on a regular basis, all confirmed either considerable development or absolute remission of “night-eating” in addition to “significant weight loss” being achieved. This has been one of the most effective treatments discovered so far, but many patients still suffered from SRED. Therefore, other treatments were sought after.

Such treatments include those targeted to associated sleep disorders with the hope that it would play an essential part of the treatment process of SRED. In Schenck and Mahowald’s series, combinations of cardibopa/L-dopa, codeine, and clonazepam were used to treat five patients with RLS and one patient with somnambulism and PLMS (periodic limb movements in sleep). These patients all were suffering from SRED as well as these other disorders, and they all experienced a remission of their SRED as a result of taking these drugs. Two patients with OSA (obstructive sleep apnoea) and SRED also reported as having a “resolution of their symptoms with nasal continuous positive airway pressure (nCPAP) therapy.” Clonazepam monotherapy was also found to be successful in 50% of patients with simultaneous somnambulism. Dopaminergic agents such as monotherapy were effective in 25% of the SRED subgroup. Success with combinations of dopaminergic and opioid drugs, with the occasional addition of sedatives, also was found in seven patients without associated sleep disorders. In those for whom opioids and sedatives are relatively contraindicated (e.g. in those with histories of substance abuse), two case reports were described as meeting with success with a combination of bupropion, levodopa, and trazodone. Notably, hypnotherapy, psychotherapy, and various behavioural techniques, including environmental manipulation, were not effective on the majority of the patients studied.

Nevertheless, Auger argue that behavioural strategies should complement the overall treatment plan and should include deliberate placement of food to avoid indiscriminate wandering, maintenance of a safe sleep environment, and education regarding proper sleep hygiene and stress management. Even with their extensive studies, Schenck and Mahowald did not find the success as Auger found by treating his patients with topiramate.

What is Night Eating Syndrome?


Night eating syndrome (NES) is an eating disorder, characterised by a delayed circadian pattern of food intake.


Although there is some degree of comorbidity with binge eating disorder, it differs from binge eating in that the amount of food consumed in the night is not necessarily objectively large nor is a loss of control over food intake required.

It was originally described by Albert Stunkard in 1955 and is currently included in the other specified feeding or eating disorder category of the DSM-5.

Research diagnostic criteria have been proposed and include evening hyperphagia (consumption of 25% or more of the total daily calories after the evening meal) and/or nocturnal awakening and ingestion of food two or more times per week. The person must have awareness of the night eating to differentiate it from parasomnia sleep-related eating disorder (SRED). Three of five associated symptoms must also be present:

  • Lack of appetite in the morning;
  • Urges to eat at night;
  • Belief that one must eat in order to fall back to sleep at night;
  • Depressed mood; and/or
  • Difficulty sleeping.

NES affects both men and women, between 1 and 2% of the general population, and approximately 10% of obese individuals.

The age of onset is typically in early adulthood (spanning from late teenage years to late twenties) and is often long-lasting, with children rarely reporting NES.

People with NES have been shown to have higher scores for depression and low self-esteem, and it has been demonstrated that nocturnal levels of the hormones melatonin and leptin are decreased.

The relationship between NES and the parasomnia SRED is in need of further clarification. There is debate as to whether these should be viewed as separate diseases, or part of a continuum.

Consuming foods containing serotonin has been suggested to aid in the treatment of NES, but other research indicates that diet by itself cannot appreciably raise serotonin levels in the brain. A few foods (for example, bananas) contain serotonin, but they do not affect brain serotonin levels, and various foods contain tryptophan, but the extent to which they affect brain serotonin levels must be further explored scientifically before conclusions can be drawn, and “the idea, common in popular culture, that a high-protein food such as turkey will raise brain tryptophan and serotonin is, unfortunately, false.”


NES is sometimes comorbid with excess weight; as many as 28% of individuals seeking gastric bypass surgery were found to suffer from NES in one study. However, not all individuals with NES are overweight.

Night eating has been associated with diabetic complications.

Many people with NES also experience depressed mood and anxiety disorders.

The Use of Ramelteon in the the Treatment of Sleep-Related Eating Disorder & Night Eating Syndrome

Research Paper Title

The efficacy of add-on ramelteon and subsequent dose reduction of benzodiazepine derivatives/Z-drugs for the treatment of sleep-related eating disorder and night eating syndrome: a retrospective analysis of consecutive cases.


The objective of this study was to determine the efficacy of ramelteon in treating abnormal eating behaviour in cases with sleep-related eating disorder (SRED) and/or night eating syndrome (NES).


The researchers retrospectively reviewed the medical records of patients with SRED/NES at Yoyogi Sleep Disorder Centre from November 2013 to November 2018. They categorised patients as ramelteon treatment responders when the frequency of night time eating per week decreased to less than half of that before treatment.


Forty-nine patients were included in the analysis. The mean frequency of eating behaviour (/week) (standard deviation) at baseline and post-ramelteon treatment was significantly different, at 5.3 (2.2) and 3.2 (3.0), respectively (p < .001). Twenty-one patients (42.9%) were classified as responders. Adverse events, all of which were mild daytime somnolence, were observed in 5 cases. There were significantly more individuals using benzodiazepine derivatives and Z-drugs (BZDs) before treatment and those with coexisting delayed sleep-wake phase disorder (DSWPD) in the responder group than in the non-responder group (p < .001 and p < .05, respectively). The mean BZD dose significantly decreased from baseline to post-ramelteon treatment within the responder group (p < .05). This trend was not observed in the non-responder group. Meanwhile, the sleep midpoint of patients with SRED/NES and DSWPD did not significantly change after treatment.


The results indicate that ramelteon is a candidate treatment for SRED/NES. The effects of ramelteon might have occurred primarily through the reduction of BZD rather than through the improvement of sleep-wake rhythm dysregulation.


Matsui, K., Kuriyama, K., Kobayashi, M., Inada, K., Nishimura, K. & Inoue, Y. (2021) The efficacy of add-on ramelteon and subsequent dose reduction of benzodiazepine derivatives/Z-drugs for the treatment of sleep-related eating disorder and night eating syndrome: a retrospective analysis of consecutive cases. Journal of Clinical Sleep Medicine. doi: 10.5664/jcsm.9236. Online ahead of print.

Book: Make Sense of Sleep: A Guide to Physical and Mental Wellness

Book Title:

Make Sense of Sleep: A Guide to Physical and Mental Wellness

Author(s): L.J. Simpson.

Year: 2021.

Edition: First (1st).

Publisher: ?.

Type(s): Kindle.


This book focuses on the importance of achieving a good nights sleep. The book focuses on all of those factors and variables that may impact your sleep, as well as those considerations that can help pave the way for a better nights rest.

This book also focuses on how to achieve and maintain good mental and physical health, while drilling into the impacts this can have on our sleep.

Linking Eating Habits & Sleep Patterns in Adolescents with Symptoms of Depression

Research Paper Title

Eating habits and sleep patterns of adolescents with depression symptoms in Mumbai, India.


Adolescents with depression engage in unhealthy eating habits and irregular sleep patterns and are often at an increased risk for weight-related problems.

Improvement in these lifestyle behaviours may help to prevent depression, but knowledge about the associations between depression, sleep, eating habits and body weight among adolescents in India is limited.


This cross-sectional study investigated the prevalence of depression and its association with sleep patterns, eating habits and body weight status among a convenience sample of 527 adolescents, ages 10-17 years in Mumbai, India.

Participants completed a survey on sleep patterns such as sleep duration, daytime sleepiness and sleep problems and eating habits such as frequency of breakfast consumption, eating family meals and eating out.

Depression was assessed using the Patient Health Questionnaire modified for Adolescents (PHQ-A).

Anthropometric measurements were also taken.


Within this sample, 25% had moderate to severe depression (PHQ-A ≥ 10) and 46% reported sleeping less than 6 h > thrice a week.

Adolescents with moderate to severe depression had significantly higher body mass index than those with minimal depression (26.2 ± 6.6 vs. 20.2 ± 4.8 kg/m2 ).

The odds of having clinically significant depression (PHQ-A ≥ 10) was 4.5 times higher in adolescents who had family meals ≤ once a week, 1.6 times higher among those who were sleeping <6 h and 2.3 times higher among participants having trouble falling to sleep more than thrice a week.


The findings indicated that a significant proportion of adolescents had depression symptoms; improving sleep and eating habits may present potential targets for interventions.


Moitra, P., Madan, J. & Shaikh, N.I. (2020) Eating habits and sleep patterns of adolescents with depression symptoms in Mumbai, India. Maternal & Child Nutrition. 16 Suppl 3(Suppl 3):e12998. doi: 10.1111/mcn.12998.

Sleep-Wake Disorders & DSM-5

Research Paper Title

Sleep-wake disorders and DSM-5.


Most individuals with mental disorders complain about the problems they experience with sleeping and waking. It is becoming evident that careful diagnosis of sleep-wake disorders is of great importance for the prevention and treatment of mental disorders. Since the introduction of the DSM-IV, clinical scientific research has provided important new insights in this field.

Therefore the aim of this research was to find out whether the new classification of sleep-wake disorders in DSM-5 is likely to improve the diagnosis of disorders of this type.


The researchers discuss the main changes in the DSM-5 classification of sleep- wake disorders, comparing the new version with the version in DSM-IV.


Because considerable attention is being given to the symptom-orientated and dimensional approach, the classification of sleep-wake disorders in the DSM-5 is closer to current psychiatric practice and it does justice to the current scientific insights into the dimensional nature of psychiatric disorders.


The DSM-5 classification takes recent scientific insights into account and might help to improve the diagnosis of sleep-wake disorders in psychiatry.


van Bemmel, A.L. & Kerkhof, G.A. (2020) Sleep-wake disorders and DSM-5. Tijdschrift voor Psychiatrie. 56(3), pp.192-195.

Reviewing Sleep & Mental Disorders in Childhood & Adolescence

Research Paper Title

Review: Sleep and mental disorders in childhood and adolescence.


Sleep problems and disorders are common in childhood and adolescence.

This review aims to throw light on the relationship between sleep problems and mental disorders in childhood and adolescence.

Sleep problems and disorders appear to be risk factors for mental disorders as comorbidities, as symptoms, and as effects of mental disorders.

Frequently, there is an interaction between sleep behaviour and psychopathology so that sleep problems contribute to the intensity and maintenance of mental disorders.

This bidirectional association is observed in early childhood as well as in school-aged children and in adolescents.

Many studies show that this association has a long-term nature beyond child development.

Both environmental and genetic factors seem to play a role in the development and maintenance of the relationship between sleep problems and mental disorders.

Various research articles show that treatment of mental disorders and treatment of sleep disorders influence each other in a positive way.

Therefore, it is strongly advised to consider sleep problems in diagnosis and treatment but also in prevention of mental disorders.


Schnatschmidt, M. & Schlarb, A. (2020) Review: Sleep and mental disorders in childhood and adolescence. Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie. 46(5), pp.368-381. doi: 10.1024/1422-4917/a000605. Epub 2018 Jul 27.

Book: Sleep Medicine and Mental Health

Book Title:

Sleep Medicine and Mental Health – A Guide for Psychiatrists and Other Healthcare Professionals.

Author(s): Karim Sedky, Racha Nazir, and David Bennett (Editors).

Year: 2020.

Edition: First (1st).

Publisher: Springer.

Type(s): Hardcover and Kindle.


Advances in sleep medicine research are improving our clinical work for individuals with sleep problems. The aim of this book is to educate psychiatrists and other mental health professionals about the importance of understanding sleep disorders, including their bidirectional relationship with psychiatric conditions.

This book consists of six major sections with seventeen chapters. It is led off by an introduction on the function of sleep, its neurophysiology, and types of sleep problems. Since insomnia represents a common and significant challenge for patients with psychiatric disorders, its clinical presentation and treatments are reviewed in the second section. Cognitive behavioural therapy for insomnia (CBT-I), mindfulness-based CBT, acceptance and commitment therapy (ACT), and the medication management of insomnia are reviewed.

A third section addresses sleep related breathing disorders. The pathology of sleep apnea, its treatments, and therapeutic modalities to address non-compliance with positive pressure ventilation are reviewed. Other sleep disorders such as hypersomnia, circadian rhythm disorders, movement disorders and parasomnias are discussed in the fourth section.

Since features of sleep disorders can vary by age, gender, and trauma history, a fifth section discusses the unique sleep problems associated with children, women, older adults, and veterans. The book concludes with a final section discussing how sleep disorders and psychiatric conditions overlap.

We hope this book highlights the importance of understanding and addressing comorbid sleep disorders among individuals with psychiatric conditions. We are confident that this book will be valuable in helping clinicians improve the management of sleep disorders in their clinical practice.