These risk factors have been distributed in three distinct categories, i.e., pharmacological triggers, psychiatric and organic predisposing or precipitating conditions, and other factors. Although the causal relationship between these factors and SRED is not confirmed by all the research cited, it was felt that mental health specialists should be warned about the potential need to screen for SRED in patients presenting these factors.

According to the current evidence in the literature, the most frequently reported comorbid conditions in patients with SRED are insomnia (58.8%), RLS (47%), sleep-disordered breathing (26%), various primary psychiatric disorders (38%), and overweight or obesity (41%) (114). As previously mentioned, outpatients with SRED and daytime eating disorders had more symptoms of other sleep disorders and higher levels of dissociation and depression than patients without SRED (80). Although the temporal sequence is unclear, because the cited study was focused on measuring the prevalence and comorbidity of nocturnal eating, not on causation, a comprehensive screening of patients with SRED for other psychiatric disorders is granted based on the available data. Also, patients with a daytime eating disorder are more likely to be diagnosed with SRED, especially hospitalized individuals, than other clinical populations (e.g., obese patients, depressed subjects) or randomly selected controls (i.e., college students) (80).

Within the SRED-diagnosed patients, the history of a daytime eating disorder is more likely, and 35% of such patients enrolled in a case series (N=23) admitted a lifetime eating disorder diagnosis (115). In another case series, 67% of the 15 patients with SRED also had bulimia nevosa, and 33% had anorexia nervosa (80).

RLS and nocturnal eating have been reported frequently as appearing together in clinical settings, but the currently available evidence could not support a causal relationship. A „restless nocturnal eating” syndrome was suggested by several authors, as a synthesis of the two clinical entities, because restlessness and nocturnal eating arise, reach their peak, and then decrease together (116).

Different parasomnias, consisting of REM sleep behavior disorders and NREMSADs, may occur in the same individual, representing the parasomnia overlap disorder (POD) (117). A 42-year-old male was diagnosed with severe OSA, sleepwalking, SRED, and sexsomnia; video polysomnography confirmed arousal from N3 sleep and an overall increase of muscle tone during REM sleep; nasal CPAP improved sleepwalking and SRED, but sexsomnia was improved only after clonazepam 0.5 mg at bedtime was administered 7 (117).

A high rate of SRED comorbidity was present in patients with narcolepsy, according to a study that included 710 patients with type 1 or type 2 narcolepsy, and idiopathic hypersomnia (118). SRED was more frequent in patients with type 1 narcolepsy (7.9%) and was associated with disrupted nighttime sleep (OR=3.9) and nocturnal eating with full awareness (OR=6.9) (118).

Weight gain and obesity may appear due to frequent nocturnal eating, and other daytime eating disorders have been described in patients with SRED (80). Significant weight gain was reported and associated with SRED, even in patients who were on a diet and regularly exercising (84). Also, being overweight was a variable detected in 44% of 38 patients within the SRED series (33, 64).

SRED and DOAs have a certain relationship, supported by the high frequency of present or personal history of sleepwalking in patients with nocturnal eating, the onset of dysfunctional eating in the first half of the night, and possible arousals from the SWS in these patients (119). Also, RLS, periodic limb movements and OSA, as well as recurrent chewing and swallowing movements during sleep, have been reported in patients with SRED who associated lack of control on the eating behaviors during the night (e.g., the ingestion of unpalatable or toxic items, like cigarettes, dishwashing liquid, or animal food) (119). All these arguments support the existence of a common pathophysiological background between DOAs and SRED, or at least a common vulnerability terrain.

The pre-bariatric surgery evaluation is recommended to include an assessment of SRED and NES. In a case report, a 38-year-old woman complained, on her sixth day after sleeve gastrectomy, about a nocturnal eating episode followed by complete amnesia (88). She woke up in the morning with the taste of food in her mouth and she found crumbs on her pillow, although she was on a strict post-surgery liquid diet She admitted she had previous SRED episodes since the age of 20, but did not seek medical help, and such behaviors were not included in the pre-surgical interview Her body mass index (BMI) was 48.9 kg/m² prior to the surgical intervention, and behaviors corresponding to NES and binge eating disorder (BED) were identified, once she was referred (post-surgery) to a specialist in eating disorders. She also reported the existence of a positive familial history, with her two brothers being diagnosed with obesity and treated with bariatric surgery, and they also presented episodes of nocturnal eating with full awareness (mean frequency of three episodes/week) (88).

Diabetes mellitus, obesity, and hypercholesterolemia have been reported in patients presenting with SRED, most likely as consequences of high-calorie ingestion during the night (53, 63, 120, 121).

This disorder may be idiopathic or it can be associated with other sleep disorders. For example, SRED has been reported in patients with RLS, OSA syndrome, and other clinical conditions (13). Also, a common pathophysiological background has been suggested for SRED and NES (121).

According to a systematic review (n=15 papers), SRED did not occur during the deep sleep phase, i.e., the N3 stage, and the explored studies could not find significant abnormalities of the polysomnographic parameters (120). Still, in other reports, a dissociated arousal in the N3 stage of sleep has also been observed in patients with SRED and was considered a vulnerability feature for parasomnias (122).

Based on these results, the utility of polysomnography in SRED is not clear, although this investigation may be helpful in differentiating SRED from other eating disorders (120). These conclusions have been based on data evaluated by the authors of the review as presenting a moderate and high risk of bias (120). Still, in a 29-year-old man, SRED had a history of six years, with nocturnal eating episodes appearing up to five/night (8–16 minutes each), and partial amnesia (92). The polysomnography recordings indicate the arising of SRED episodes from N2 NREM sleep, with maintenance of this sleep stage throughout the entire episode, or with wakeful EEG, but without epileptiform activity (92).

In a study that enrolled 23 patients presenting SRED (83% female), the polysomnographic recordings showed the presence of somnambulism in almost 50% of the cases (115). Also, 35% of these patients had a lifetime history of eating disorders. More than 90% of the patients with SRED reported they were „half-awake, half-asleep” during the eating episodes, with significant or partial amnesia of the events. Most of the patients had an onset of their SRED during adolescence and a chronic evolution, with a history of 15.8+/-11.2 years (115). In conclusion, SRED combines features of somnambulism and eating disorders.

A study (N=35 drug-free patients with nocturnal eating) used video polysomnographic recordings in a sleep laboratory to detect the neural signatures of the SRED or NES (123). The vast majority of the patients presenting nocturnal eating in lab settings were fully awake during their episodes, and the onset of the dysfunctional behavior was observed after non-REM sleep; only one patient had the onset of this behavior during awakening from REM sleep (84). All patients presented alpha activity on their EEG and no dissociated features during their nocturnal eating These patients had a history of sleepwalking (N=1), somniloquy (N=5), RLS (N=8), and periodic limb movements during sleep (N=4) (84). During lab conditions, periodic limb movements were present in 22 patients, RLS dyskinesias in 5 patients, and recurrent chewing and swallowing movements during sleep in 29 patients (123).

The relation between glucose metabolism and SRED was explored from a pathophysiological perspective. A decrease of this metabolism at the cortical level during physiological sleep was reported, but in zolpidem-induced sleep, this correlation was not supported by evidence (53). This observation suggests that some instinctive behavioral patterns related to survival may be abnormally activated during the administration of zolpidem, a drug frequently invoked as an SRED trigger (53, 59). Another theory suggests that SRED induced by zolpidem is a consequence of this drug’s inhibitory activity on the serotonin neurotransmission at the hypothalamic ventrolateral nucleus, which controls the food appetite, or at the level of raphe nuclei, which changes their activity depending on the feeding status (53). On video-polysomnography, chewing and swallowing movements during N2 sleep have been reported in patients with SRED (122, 123). It was hypothesized these behaviors may represent an anticipation of the reward, represented by eating, similar to the results of translational research (122).

The enhancement of GABA-ergic activity especially at the α-1 subunits of GABA-A receptors, determined by Z-drugs, increases the risk of complex sleep behaviors onset (45). The amnesia that follows such behaviors is also a possible consequence of GABA-ergic enhancement, a phenomenon that inhibits the consolidation of short-term memories. Therefore, lowering the dose, discontinuation, or switching to another drug are recommended in patients treated with Z-drugs who develop such complex sleep behaviors (45).

Serotonin (via 5HT2 receptors) may have an inhibitory effect in controlling SWS (73). Atypical antipsychotics may increase SWS due to the reduction of serotonergic transmission A decrease in the dopaminergic neurotransmission is also a possible cause of SRED that may explain the association of certain antipsychotic drug use with new onset SRED (73).

The decrease in dopaminergic and/or serotonergic activity may be a factor that leads to SRED (89). The co-occurrence of RLS and SRED supports the involvement of dopaminergic dysfunction in these patients (75).

High levels of novelty seeking, exploratory excitability, and increased reward sensitivity were reported in a case series (N=2) of patients with SRED (122). Because compulsive eating disorders have been associated with a more intense mesolimbic dopaminergic sensitivity, it was hypothesized that the activation of the reward system during sleep makes the individual more vulnerable toward the onset of nocturnal overeating, especially in the presence of high novelty seeking and reward sensitivity. Motor disinhibition during nighttime, typically met in parasomnias, combined with the arousal of regions within the reward system, can explain the onset of SRED (122).

There is a distinct possibility that an internally generated stimulus can determine partial arousal and, if this arousal occurs during non-REM sleep, in an individual with a certain predisposition, may induce a nocturnal eating episode (72, 115). Hypoglycemia or unconscious emotional stimuli may be triggers for eating in inappropriate conditions (72, 124).

Genetic factors may contribute to the vulnerability to „disorders of arousal”, but evidence to support this hypothesis is insufficient (14). In a case report, SRED was detected in the index case and her fraternal twin sister and father, supporting the claim of a genetic vulnerability (125). The index case did not respond to clonazepam, but responded to an OTC for cold, containing pseudoephedrine hydrochloride, dextromethorphan hydrobromide, doxylamine succinate, and ethyl alcohol (125).

An important differential diagnosis is represented by the night-eating syndrome (NES), which refers to patients who are unaware of the time and quantity of food they eat (32). NES is considered by several authors a non-motor group of clinical manifestations related to RLS (32). In the seminal work by Stunkard et al. (30), NES was reported as an eating pattern defined by nocturnal hyperphagia („the consumption of large amounts of food during the evening and night… (of) at least a quarter of (their) total calories for the day during the period following the evening meal”), insomnia („sleeplessness, at least until midnight more than half of the time”), and morning anorexia („negligible food intake at breakfast”) in a group of 25 individuals with obesity, who were compared to 38 individuals without a history of weight disorder (30). According to the DSM-5TR criteria, NES is included in the category of „Other specified feeding or eating disorder” (9). This is considered progress in the way of achieving an independent nosological status for NES, because in the previous edition, DSM-IV-TR, this disorder was included in the category of „Eating disorders not otherwise specified” (126). According to the DSM-5TR, for diagnosing NES, the following criteria should be present: recurrent episodes of night eating (eating after awakening from sleep or excessive food ingestion after the evening meal), awareness preserved about the eating episodes, the recall of such episodes is possible, there are no external influences in the sleep-wake cycle or changes in local social norms, there is significant distress and/or impairment of functioning, and there is no other medical, substance-related, or psychiatric condition that may better explain these symptoms (12). SRED patients had more clinical manifestations suggesting a sleep disorder, more severe depression, and more intense dissociation than patients with NES, according to a study evaluating the comorbidity in patients with night eating, without focusing on a causality relationship (80). Other authors report higher scores on physical tension, mood, and sleep dysfunctions in relation to NES than in relation to SRED, with no significant differences in age, BMI, or gender distribution (127).

In a clinical comparison that explored the medical records of 30 patients with primary SRED and 10 patients with drug-induced SRED (pharmacological agents with sedative properties, mainly zolpidem or benzodiazepines), a higher mean age of onset (40 vs. 26-year-old), higher rate of total amnesia (75% vs. 32%), lower rate of comorbid NES (0% vs. 63%), and lower rate of sleepwalking history (10% vs. 46.7%) were present in patients with drug-induced SRED (128). The combination of multiple types of sedative agents was observed in all patients with SRED induced by drugs (114). Higher doses of benzodiazepines may be responsible for the onset of SRED. The polysomnography recordings showed in drug-induced SRED a longer sleep-onset latency and a lower duration of deep sleep, possibly related to insomnia or pharmacologic effects of sedatives in these patients (128). Unlike SRED, the existence of drug-induced NES was not demonstrated (59).

During the SRED episodes, unlike during NES, edible and non-edible items can be consumed, and a mixture of these types of items is also possible. For example, in a patient with SRED (unspecified gender or age), easily accessible foods (milk, candies, fruits, or leftovers) were consumed in a disorganized manner, but the tentative consumption of a self-prepared meal consisting of bread and dishwashing liquid was the fact that alerted the family and led to the specialized consultation (129).

There is a controversy in the literature about the differences between NES and SRED, and whether the two disorders are, in fact, a single syndrome or two distinct disorders (130). Although both disorders involve dysfunctional eating behavior during the nighttime, with high-calorie intake and multiple awakenings, higher prevalence in women and possible familial aggregation, there are still several significant differences: the level of consciousness during the eating episodes (full awareness in NES vs. partial/complete lack of awareness in SRED) with consecutive full remembrance of the episodes (in NES) or impaired recollection about them in the following morning (in SRED) (116). One hypothesis states the two entities are, in fact, a single disorder, considering that sleep disorders specialists and eating disorders specialists focus their research on the same dysfunctional eating behavior, but from different perspectives, thus creating the impression of two distinct pathologies. According to this hypothesis, SRED is just an epiphenomenon of sleepwalking, while NES is a type of binge eating disorder with nocturnal manifestations (130).

The differential diagnosis of SRED also involves other conditions characterized by the presence of abnormal eating during nighttime (131). Kleine-Levin syndrome (KLS), defined by a fluctuating course and an onset during adolescence, is a rare disease with episodes lasting from one to several weeks, and its core manifestations are hypersomnia, confusion, slowness, amnesia, derealization, and apathy (132). The pathophysiological substrate is supposedly recurrent inflammatory encephalitis, but a genetic component is also suggested by the fact that 5% of cases are familial (132). The confusion with SRED may arise from the hyperphagia observed in patients with KLS because 2/3 of them have episodes of compulsive eating, which can be reported during their sleep (132).

BED and episodes of nocturnal eating in patients with bulimia nervosa also need to be explored in the context of a differential diagnosis of SRED (131). Recurrent episodes of binge eating are characteristics of BED and bulimia nervosa, but compensatory behaviors targeting weight gain prevention are typical only for bulimia nevosa (12). Because these binge eating episodes may be present not only during daytime, SRED should be included as a potential differential diagnosis. However, while such episodes are accompanied by partial or complete amnesia in patients with SRED, in bulimia nervosa and BED the patients are fully aware of their behavior.

Dissociative disorders may involve episodes of eating followed by amnesia, including during nighttime (131). These disorders disrupt the continuity of integrating data into consciousness and impair the functionality of memory, perception, motor control and behavior, therefore creating confusion between SRED and dissociative eating behaviors (12). Still, dissociative disorders are complex, and their symptoms are virtually never limited only to eating behaviors.

The distinction between non-dysfunctional nocturnal eating (NDNE) and SRED is important, in order to avoid stigmatization and the tendency to over-pathologize normal behaviors. Non-dysfunctional nocturnal eating is presumed to be a non-pathological variation of SRED or a subtler form of SRED (32). Although a clear definition of NDNE could not be retrieved in the literature, based on the existing studies, it may be considered that in this case, the core criteria of SRED are not met. For example, those criteria referring to partial/complete amnesia of eating episodes, the possibility of ingesting nonedible items, or potentially dangerous behaviors due to automatic behaviors are not met in NDNE (26, 30). The confusion between SRED and NDNE may arise from the nocturnal eating episodes and from the adverse negative effects on one’s own health, like obesity or metabolic syndrome.

In patients with eating disorders, depression, or obesity, an estimated 4–5% prevalence of SRED was based on epidemiological studies (80). Hospitalized patients with eating disorders have a much higher prevalence of SRED than outpatients with such pathology and the control group (16.7% vs. 8.7% vs. 4.6%) (80).

A majority of women (67.6%) were reported in a study evaluating the demographical characteristics in a group of 23 patients with SRED (114). This gender distribution was confirmed in another study (N=15 patients with SRED), and the onset of the disease was in adulthood (86). In a review of zolpidem-related-SRED cases (N=40), the majority of patients were also females (65%), who used high doses of this drug (10–30 mg in 95% of the situations) (50). According to this review, these patients also had a high percentage of concomitant SSRIs or benzodiazepines use (~57%) (50). Several authors correlated this higher incidence of SRED in women with the higher rate of daytime eating disorders (121).

The mean duration from the first SRED symptoms until the moment of diagnosis was 39+/-13.8 (17–67 years) (114). Other authors considered the average duration from the very first signs up to the first contact with healthcare systems, to be 12–16 years (131). Also, the onset of SRED was reported between adolescence and young age, with most of the patients presenting a chronic course (121). The average age of SRED onset was estimated to be between 22 and 27 years (131).

According to a cross-sectional survey conducted in a Hong Kong outpatient clinic, by interviewing 1235 subjects, a 4% lifetime prevalence of SRED was calculated, compared with 8.5% for sleepwalking, while the 1-year prevalence was 2.4%, and 2.9%, respectively (133). These conditions were associated with depression and various other sleep disorders Sedative antidepressants (tricyclics, trazodone, and mianserin) and nonbenzodiazepine hypnotics (zolpidem and zopiclone) were associated more frequently with sleepwalking, while zolpidem and antidepressants with SRED (133).

Many sources highlighted the chronic evolution of SRED, prior to the treatment initiation (33, 115, 134).

The Inventory of Nocturnal Eating (INE) was developed to evaluate both night eating behaviors and sleep quality (80). It is a self-administered questionnaire and comprises seven sections, with an unspecified number of items (64). If any nocturnal eating is detected, its frequency and awareness are further explored The interpretation allows differentiation of eating behaviors during sleep and nocturnal eating without loss of consciousness. The communicated inventory’s sensitivity was 0.91 (80).

A questionnaire dedicated to parasomnias and nocturnal behaviors, Munich Parasomnia Screening (MUPS), is based on 21 different clinical manifestations (translated into an equivalent number of questions) and it is self-assessed (135). This instrument allows for assessing the lifetime history or frequency of each manifestation on a Likert scale with seven options (121). This instrument’s sensitivity and specificity were >75% (135). Sleep-related eating is evaluated on this questionnaire distinctly from nocturnal eating and confusional arousals. The fact that SRED and all the other parasomnias can be assessed with a single instrument is very helpful for clinicians, although this instrument is not widely used. A Japanese version of MUPS was validated by Komada et al. (136) and the estimated time to complete this questionnaire was calculated to be 8 minutes (range 2–17 minutes) (136).

The Night Eating Questionnaire (NEQ) was created to assess the severity of NES, and it can be a useful instrument for differentiating SRED from NES. This questionnaire comprises 14 items, assessed on a 5-point Likert scale, for quantifying behavioral and psychological symptoms of NES and has a Cronbach alpha value of 0.70 (137). A four-factor structure was supported by the analysis, with nocturnal ingestions, evening hyperphagia, morning anorexia, and mood/sleep confirmed as the main dimensions of NES. The original, unpublished version of NEQ contained only nine items, assessed on a 4-point Likert scale, and evaluated morning anorexia, evening hyperphagia, initial insomnia, mid-phase insomnia, nocturnal ingestions, and mood (137).

A self-rating scale (Paris Arousal Disorders Severity Scale, PADSS) containing items that describe 17 parasomniac behaviors, assessed for their frequency and consequences, was designed mainly for the evaluation of sleepwalking and sleep terrors but also included descriptors of other NREMSADs (138). This scale has demonstrated high sensitivity, specificity (patients with non-REM vs. REM parasomnias and patients with arousal disorders vs. normal controls), internal consistency, and test-retest reliability, with a cut-off for the total score of 13/14 for non-REM parasomnias. Two components were identified by factor analysis, i.e., „wandering” and „violence/handling. The behaviors emerging from N3 sleep (demonstrated on video-polysomnography) correlated with PADSS total scores, its subscales, and the „violence/handling” factor. PADSS includes an item for SRED (with complete amnesia) that can be rated as „never”, „sometimes”, or „often”, with a self-estimated frequency of the eating episodes over the last year (from none to two or more episodes per night), and for the negative functional/emotional consequences of these behaviors (138).

None of these three instruments can be considered specific for evaluating SRED, but they can be useful for screening purposes (i.e., detecting nocturnal eating behaviors) as a preliminary step to a more detailed evaluation. Also, NEQ may be used to differentiate SRED from NES by providing a severity score for the last diagnosis, and PADSS may distinguish between non-REM and REM parasomnias.

The treatment of DOAs is still largely based on the prevention and removal of precipitating factors as well as on clinicians’ personal experience with similar cases (14). In patients where the onset of SRED can be related to the presence of sleepwalking, periodic limb movements, substance use disorders, chronic autoimmune hepatitis, narcolepsy, encephalitis, or acute stress reaction, these conditions should be adequately treated, as an essential stage of the SRED management (33). In patients with sleepwalking, almost 73% had their nocturnal eating and other sleepwalking behaviors suppressed by the administration of clonazepam and/or bromocriptine treatment. Patients with periodic limb movements and SRED responded favorably to combinations of carbidopa/l-dopa, codeine and clonazepam (33). CPAP may be a useful method to approach non-pharmacologically patients with SRED and associated OSA (89), but evidence-based recommendations for the utility of such a therapy are sparse (64, 90). In two reported cases of SRED and OSA dual diagnosis, CPAP succeeded in controlling nocturnal eating behaviors (90). However, efficient treatment of the primary sleep disorder can lead to remission of nocturnal eating behaviors in a significant proportion of cases, therefore any therapy targeting the primary sleep disorder is granted (33, 89).

According to a 2019 literature review, none of the explored treatment options for NES or SRED have proven their long-term efficacy in good-quality studies (93). Lack of information about the existence of SRED among clinicians and a possible under-reporting of this condition by patients may be plausible causes for the lack of evidence-based therapeutic recommendations (93).

However, based on very limited data, first-line treatment for SRED includes SSRIs, with topiramate or clonazepam as alternative options (13). Clonazepam 1 mg at bedtime decreased the nocturnal eating behaviors in a 48-year-old Japanese woman, although her sleepwalking remained (63). Adding pramipexole 0.125 mg to clonazepam improved SRED, RLS, and sleepwalking manifestations (63). Also, clonazepam treatment completely eliminated the episodes of RLS and nocturnal eating in a 51-year-old female patient with schizophrenia (67).

The combination of dopaminergic and opioid agents has also been described as a treatment for SRED, in a series of seven cases (94). Occasional use of sedatives was allowed in these patients, although no associated sleep disorders were detected (94). Dopaminergic agents (carbidopa/l-dopa, bromocriptine) +/- codeine and clonazepam led to favorable results in cases of SRED associated with sleepwalking or periodic limb movement in a series of 19 adults (64).

In a 35-year-old male with a dual diagnosis of obesity and SRED, the initiation of phentermine and topiramate ER led to favorable results after five months of combined treatment, with 5% weight loss and remission of dysfunctional eating behaviors (95). However, after the patient’s self-initiated treatment discontinuation, the SRED symptoms reappeared (95). Topiramate (flexible-dose up to 300 mg) was explored in a 34-patient randomized clinical trial, which enrolled participants with SRED (mean duration of their disorder 13.7 years) (96). After 13 weeks, the primary outcome (percentage of nights with eating behavior) was significantly improved by topiramate vs. placebo and baseline values. More responders to topiramate, as assessed by the Clinical Global Impression-Improvement (CGI-I) scale, than to placebo, were observed, and the level of wakefulness and memory of episodes predicted the favorable therapeutic response for nighttime eating at baseline. Also, the body weight decreased more during topiramate treatment vs. placebo, while paresthesias and cognitive dysfunction were the most frequently reported adverse events (96).

In yet another report, 12 out of the 17 enrolled patients diagnosed with SRED who received topiramate had a favorable outcome and tolerated this drug well over 1.8 years (97). In a case series, two patients diagnosed with SRED and two with NES, with a history of non-responsivity to multiple trials of pharmaco- and psychotherapy, received open-label, naturalistic, treatment with topiramate at bedtime (98). One patient with SRED had a marked response, and one had only a moderate response, based on clinical outcomes The benefits of topiramate treatment were still observed after 8.5 months (98). Also, in a 45-year-old woman diagnosed with sleepwalking, SRED, who also presented sleep-related smoking (none of these confirmed on video polysomnography) and had a history of mild OSA, topiramate (25 mg/day initially, titrated up to 100 mg/day, at bedtime) led to complete resolution of all three pathological nocturnal behaviors; these positive results persisted at 10-month follow-up (99).

A retrospective chart review explored the effects of topiramate in 30 patients with SRED, using as an outcome the variations of Clinical Global Impressions of Improvement (CGI-I); after an 11.6 months mean duration of treatment with topiramate (mean dose 135+/-61.6 mg daily), 68% of the patients were considered responders (CGI-I scores „very much” or „much” improved) (100). The tolerability of topiramate in this study was not very good, and adverse events were reported by 84% of these patients, while more than 40% discontinued the treatment after a mean duration of 12.4 months (100).

Topiramate was efficient in a 28-year-old man who suffered from SRED and sleepwalking with daily episodes for ten years (101). He was overweight and had a personal and familial history of other sleep disorders. After the failure of clonazepam (2 mg/day) and fluoxetine (20 mg/day), topiramate up to 50 mg/day was initiated and led to the complete disappearance of SRED manifestations. Although isolated episodes of sleepwalking remained, the treatment was well tolerated, and after two years, there was no recurrence of nocturnal eating (101).

Sertraline (low dose, 25 mg daily) taken at bedtime induced complete and prolonged (up to 9–17 months) remission of SRED symptoms in two patients (males, 36 and 37-year-old) who had this disorder for 3 and 7 years, respectively (84). SSRIs (fluvoxamine and paroxetine) were efficient in a 4-case study with SRED-diagnosed patients (102). Fluoxetine was efficient in 2 out of 3 patients in a case series of SRED (N=19) (64).

In a case report, agomelatine controlled the sleep-related eating symptoms in a 54-year-old woman diagnosed with depression, panic disorder, SRED, and sleep apnea (103). After cessation of agomelatine treatment, the SRED symptoms reappeared, but they were remitted again after reinitiating the melatoninergic antidepressant.

When SRED is connected to RLS, dopamine agonists (e.g., pramipexole) could be recommended, and sleepwalking-related SRED may benefit from low doses of clonazepam (13). Pramipexol (0.18–0.36 mg) was evaluated in a placebo-controlled study with 11 consecutive patients diagnosed with SRED who did not present daytime comorbid eating disorders (91). After two weeks of treatment, the median night duration of abnormal behavior decreased, and the number of nights with restorative sleep during each week significantly improved. Also, the tolerability of this D3-agonist was good, and no withdrawal from the study was recorded (91).

A combination of bupropion, l-dopa, and trazodone was associated with good results in a case series (N=2 patients with SRED, monitored with polysomnography), in individuals with a personal history of substance use disorders (alcohol, cocaine +/- tobacco) but without other comorbid sleep disorders (104). These two received carbidopa/l-dopa monotherapy without significant effect, but full control of nocturnal eating and nocturnal awakenings was obtained after the addition of bupropion and trazodone. Also, in one case, a significant weight loss was reported and maintained at a one-year follow-up (-6 kg to baseline) (104).

Replacement of benzodiazepines with other, non-GABA-ergic pharmacological agents, can be beneficial in decreasing and eliminating the occurrence of SRED episodes. For example, suvorexant, a selective dual antagonist of the type 1 and 2 orexin receptors (OX1 and OX2), demonstrated efficacy in a 25-year-old woman diagnosed with depression, who presented episodes of night eating with partial or complete amnesia and sleepwalking for one year (105). This patient was diagnosed with SRED based on polysomnography, which detected an awakening from the N2 stage sleep from eating. She was recommended to discontinue brotizolam (0.25 mg) and was switched on to suvorexant (10 mg), which led to a complete disappearance of SRED. During the 2-year monitoring period, she did not present any new SRED manifestations (105).

A retrospective study (N=49 patients) reported on the efficacy of ramelteon as an add-on to the ongoing benzodiazepine treatment, followed by dose reduction of benzodiazepine, as a strategy for patients with SRED (N=45), NES (N=41) or both (N=37) (106). The introduction of ramelteon (4–8 mg/day) led to a mean decrease in nocturnal eating behavior per week from 5.3 to 3.2, and 43% of these patients were responders. Only five patients reported adverse events, consisting of mild daytime somnolence. Also, the mean benzodiazepine and Z-drugs dose (brotizolam, clonazepam, eszopiclone, etizolam, flunitrazepam, loflazepate, triazolam, zolpidem, and zopiclone) decreased significantly from baseline to the post-ramelteon phase (i.e., mean duration of 11.7 months of ramelteon treatment), but only in the responders’ group (106).

A regular follow-up is recommended for all patients with SRED, at least 2–3 times per year, using clinical evaluations and structured interviews to monitor the treatment’s efficacy and its adverse events (13).

Psychotherapy was also tried for patients with parasomnias, SRED cases included. In a study with 36 patients, out of which two were diagnosed with SRED, received one or two hypnotherapy sessions, followed by regular visits up to 5 years (107). Although the overall rate of response was good, with more than 45% at the 1-month visit and more than 40% at the 5-year follow-up free of symptoms or much improved, SRED cases were much improved only in 50% of the cases after 5 years (107). However, due to the small number of patients with SRED, the significance of this percentage is difficult to assess. In a case series of parasomnias, a 38-year-old female with sleepwalking and nocturnal binge-eating episodes reported amnesia for nocturnal eating behaviors; these sleep-eating episodes occurred 2–3 times/week (108). Two sessions of hypnotherapy included suggestions about waking up, feeling calm and safe, and going back to bed when her feet touched the floor or opening the fridge door. The episodes of sleepwalking/SRED significantly decreased (only one episode during a month was reported) (108).

The efficacy of cognitive-behavioral therapy (CBT) for SRED was not systematically assessed in clinical trials. However, there are studies that enrolled patients with SRED in parasomnias-focused CBT that may appear promising (109, 110). CBT-NREMP (CBT for non-REM parasomnias) is a new type of therapy, group-based, focused on decreasing parasomnia severity during a limited number of sessions (109). CBT-NREMP is a development of CBT for insomnia (CBT-I) approach that includes psychoeducation on non-REM parasomnias, sleep hygiene, sleep rescheduling, stimulus control, and specific body-based and relaxation interventions (109). In such a study, 46 patients with NREMSAD (out of which one presented SRED) received a 5-session group-based CBT-NREMP program, and a significant reduction in the outcomes (clinical measures of NREMSAD, insomnia, and anxiety and depression) was observed (109, 110). However, due to the very small number of patients with SRED in this study’s group, it is difficult to extract definitive conclusions on this specific pathology. According to a systematic review of CBT for parasomnias, this type of psychotherapy is ineffective when compared with pharmacotherapy, but the authors acknowledge there is no direct comparison between the two types of interventions in SRED in clinical trials, and their observation is based on a single report (64, 110).

Offering limited access to food before going to bed was associated with modest benefits in a 29-year-old man with a history of 6 years of SRED (92). Another report to support this recommendation refers to a 34-year-old white man, who presented SRED behaviors with a frequency of 2–3 episodes/night, followed by complete amnesia, with the onset of SRED after a motorcycle accident (83). After an incarceration of 1.5 years, he lost 36 kg due to the inaccessibility to food during nighttime. After his release from prison, he gained 40 kg, and SRED episodes were again witnessed by his wife (83).