Sleep-related eating disorder with mirtazapine

Abstract

Sleep-related eating disorder (SRED) is classified within parasomnia and is characterised by recurrent episodes of abnormal, dysfunctional eating during sleep. This report describes a case of SRED in a 19-year-old woman admitted to the psychiatric ward with worsening anxiety, low mood and suicidal ideation. She was started on low-dose mirtazapine for mood stabilisation and, following an incremental increase to 30 mg, she developed nocturnal binge eating of which she retained only partial memory on waking. She developed adverse health consequences as a result of these recurrent episodes. The subject’s symptoms were relieved rapidly following reduction of the dose of mirtazapine back to 15 mg.

Background

Sleep-related eating disorders (SRED) have been described with medication use in the past, in particular with zolpidem use.^{1 2} However, there has only been one report linking this disorder to mirtazapine use in current literature,.³ Here, we describe a second case whereby a young woman, started on mirtazapine for her mood, describes episodes of binge eating during the middle of the night. This began soon after the medication dose was increased and subsequently relieved following dose reduction. After discussion with a number of psychiatrists, it appears that, anecdotally, this observation may be more common than initially thought and hence it is important that such cases should be published with the view that this behaviour becomes a recognised side effect of mirtazapine. We have alerted the yellow card scheme regarding the aforementioned side effect.

Case presentation

The subject of this case report is a 19-year-old woman who was admitted to the psychiatric ward with worsening anxiety, low mood, deliberate self-harm and suicidal ideation. She had previously been under the care of the community mental health team and was prescribed venlafaxine for her anxiety. She was also known to the neurology team, who had advised long-term lamotrigine, earlier this year for generalised seizures and concurrent mood stabilisation. Unfortunately, however, she had been non-compliant in taking either of these medications regularly.

During the acute admission, the subject was initially restarted on venlafaxine 75 mg once daily and the dose gradually increased to 150 mg once daily. She was also restarted on lamotrigine 75 mg once daily. Alongside these medications, she was also given her regular inhalers for asthma, Spiriva 5 mcg once in the morning and salbutamol as needed. She receives monthly omalizumab injections under the respiratory team for her brittle asthma.

The patient reported that venlafaxine was helpful for her anxiety, but she did not feel a benefit in terms of mood improvement, and it was decided that she should start mirtazapine 15 mg once at night in addition to the venlafaxine, with the view of increasing the dose after 3 days to 30 mg once at night.

At the next ward review 5 days after this increase was made, the patient reported problems with her sleep as she was waking up in the early hours of the morning, but reported she was able to return to sleep easily and no changes were made to her medications. The following day she reported that she had experienced an episode of nocturnal binge eating which she did not fully recollect on waking. She reported that she had consumed multiple packs of crisps, boxes of biscuits and any other food that was left by her bedside, and the evidence was the empty packaging she found in the morning. These episodes continued while she was on the higher 30 mg dose of mirtazapine, on occasion leading to abdominal pain and vomiting during the night.

During the 2 weeks and 3 days the subject was on this increased dose, she reported a 4 kg weight gain. The subject reported this significant weight gain as her weight was usually very stable, and it was very unusual for her, but she denied any body dysmorphia or symptoms of eating disorders. There was also no history of restless leg syndrome or any other parasomnia in the past.

These episodes subsided the day after the dose of mirtazapine was reduced back to 15 mg, and she reported no further episodes of binge eating or sleep disturbance.

Differential diagnosis

Night eating syndrome is a clinical condition whose symptomatology overlaps with SRED.⁴ However, in view of no reported insomnia and no full memory of the eating, this can be excluded.⁵

Treatment

The symptoms subsided following reducing the dose of mirtazapine to 15 mg.

Outcome and follow-up

The subject was reviewed on the third day following reducing mirtazapine to 15 mg; she reported no symptoms of SRED. She was again reviewed weekly for 2 months and reported no further symptoms of sleep eating.

Discussion

SRED is classified within the parasomnias which is an abnormal and undesirable phenomenon that occurs during sleep.⁶

According to the International Classification of Sleep Disorders III,⁴ the diagnostic criteria for SRED include recurrent episodes of dysfunctional eating after an arousal during the main sleep period along with the presence of at least one of the following: (1) Consumption of peculiar forms or combinations of food or inedible or toxic substances. (2) Sleep-related injurious or potentially injurious behaviours performed while in pursuit of food or while cooking food. (3) Adverse health consequences from recurrent nocturnal eating. There is partial or complete loss of conscious awareness during the eating episode and subsequent impaired recall. This disorder can be differentiated from night eating syndrome which is characterised by conscious eating after awakening from sleep.

Our subject met the criteria for SRED. She had been binge eating nocturnally after falling asleep, of which she had only partial memory on waking. She had adverse health consequences as a result of binge eating, such as nausea and vomiting, and had significant weight gain. The onset of this SRED correlated with increasing the dose of mirtazapine.

On literature review, we noted that another case of SRED with mirtazapine³ has been reported in South Korea. The case reported a 24-year-old woman who experienced SRED following being started on mirtazapine, and the symptoms subsided after stopping the same.

The exact pathophysiology of SRED is unknown.⁵ Mirtazapine antagonises presynaptic alpha 2 receptors thereby increasing noradrenergic and serotonergic transmission, especially at 5HT1A.⁷ The 5HT2 and 5HT3 serotonin receptors are blocked postsynaptically. Mirtazapine at low doses also has a potent antagonist effect on histamine 1 receptors which may augment the sedative and appetite-increasing effects. The noradrenergic properties of mirtazapine could potentially increase extracellular dopamine in the prefrontal cortex.^{8 9} It is uncertain which mechanism of mirtazapine exactly causes SRED or whether it is a combination of the above.

Many other psychotropics are also known to cause SRED, among which the hypnotic zolpidem has been reported in 37 case reports.¹⁰ There have also been case reports on olanzapine, quetiapine and risperidone causing SRED.^11–13 Sleep studies have indicated that SRED is also known to be associated with other sleep disorders such as sleep walking, narcolepsy, periodic limb movement disorder and restless leg syndrome.

In conclusion, this case describes a rare but important adverse effect of mirtazapine. Clinicians should be aware of this potential side effect and consider it when a patient reports sleep disturbance and weight gain. Given that this is the second case report on this adverse effect of mirtazapine, it could be much more frequent than currently recognised. More studies are needed to understand the mechanism of mirtazapine causing SRED. It is also important to keep in mind the other medications that can cause SRED and be cautious, especially when used in combination.

Patient’s perspective.

“After I began taking mirtazapine 15 mg, I noticed an increase in appetite although it did not concern me. Once the dose was increased to 30 mg I began experiencing episodes of eating during the night. I would wake up the next day surrounded by wrappers of food I had eaten. Sometimes I may recall waking in the night and eating 1 piece of food (eg, one biscuit or one apple), but not any of the other food I had consumed, on other occasions I would not remember waking or eating at all. By looking at the wrappers that were present in the morning I would estimate I was eating between 600 and 1200 calories during every instance of this. I was also still having an increased appetite during the day. Over the few weeks in which I was having these episodes I put in quite a substantial amount of weight. I remembered a few occasions waking up later in the night (after an episode of eating) and throwing up due to sheer amount of food I’d eaten. The night after the mirtazapine was reduced to 15 mg I stopped experiencing these episodes.”

Learning points.

• Mirtazapine can cause sleep-related eating disorder (SRED) as a side effect.

• Monitor weight gain for people on mirtazapine.

• Pay particular attention to sleep disturbances when prescribing mirtazapine.

• Remain vigilant on organic causes of SRED.