Successful Treatment of Somnambulism With OROS-Methylphenidate

Abstract

Somnambulism is a non-rapid eye movement sleep parasomnia with potential for significant injury as well as functional nighttime and daytime impairment. Clonazepam is frequently used as first line pharmacotherapy. However, the optimal treatment of somnambulism has not been established. In this article, we present the cases of two patients with severe somnambulism who showed a significant therapeutic response to osmotic release oral system methylphenidate (OROS-MPH). In addition to its practical therapeutic implications, this first report of the successful treatment of somnambulism with OROS-MPH may provide additional insight into the neurobiological underpinnings of this medical condition.

Citation:

Nigam M, Zadra A, Boucetta S, Gibbs SA, Montplaisir J, Desautels A. Successful treatment of somnambulism with OROS-methylphenidate. J Clin Sleep Med. 2019;15(11):1683–1685.

INTRODUCTION

Somnambulism is a non-rapid eye movement (NREM) sleep parasomnia defined by the International Classification of Sleep Disorders (ICSD) as a disorder of arousal usually initiated during partial arousals from slow-wave sleep (SWS) and associated with ambulation and other complex behaviors out of bed. Common during childhood, the overall prevalence of sleepwalking in adulthood is estimated at 2% to 4%.¹ While frequently benign in children, somnambulism in adults may require treatment as it is associated with a risk of injury as well as functional daytime impairment. No randomized clinical trials assessing treatment options for somnambulism have been undertaken and current therapies are based on case series and small, uncontrolled trials. In addition to recommending measures to increase patients’ safety during their episodes, clonazepam is recommended by most sleep physicians as first line treatment for somnambulism,^2,3 though controlled trials are lacking. In this article, we present the cases of two adult sleepwalkers successfully treated with osmotic release oral system methylphenidate (OROS-MPH).

REPORT OF CASES

Patient One

A 24-year-old woman presented to our sleep clinic with a history of longstanding primary parasomnia. The events began at age 5 years and were characterized by somnambulism sometimes accompanied by recall of episode-related sleep mentation, somniloquy and occasional nocturnal eating. At the time of her consultation, these events were occurring once or twice per week, typically in the first third of the night, and were troubling to her and her bedpartner. The patient also complained of daytime sleepiness and reported a past medical history of migraine with visual aura. She reported a positive family history of somnambulism in her mother and no previous history suggestive of restless legs syndrome (RLS) or sleep-disordered breathing. The patient took no medication other than levonorgestrel-releasing intrauterine device.

Overnight polysomnography (PSG) with full electroencephalography (EEG) was performed as per our center’s protocol for NREM parasomnias. PSG revealed two confusional arousals (characterized by sitting up in bed and looking around) emerging from stage N3 sleep with an otherwise preserved sleep architecture and no evidence of sleep-disordered breathing (apnea-hypopnea index [AHI] 0.1 events/h) or epileptiform activity. The periodic leg movements during sleep index (PLMSI) was elevated at 53 events/h of which 10.4 events/h corresponded with microarousals. A second recording performed after 24 hours of sleep deprivation revealed 7 episodes of confusional arousals emerging from stage N3 sleep and the PLMSI was 15 events/h of which 1.95 events/h were associated with microarousals.

Treatment with OROS-MPH was initiated at a dose of 18 mg taken in the morning. Shortly after beginning the OROS-MPH, the patient and her bed partner reported a complete resolution of her somnambulism. Interestingly, they spontaneously reported that her early night sleepwalking episodes appeared to have been replaced by complete and transitory awakenings. After an initial 4-month period of complete remission, a relapse occurred. At this point the OROS-MPH dosage was increased to 36 mg.

The patient, after taking OROS-MPH for 5 years, reported a continued efficacy and tolerability of the medication, with residual events occurring once or twice every 6 months, primarily in the context of sleep deprivation or stress exacerbations. She also reported a maintained improvement in her daytime sleepiness.

Patient Two

A 34-year-old woman presented to our sleep clinic with a history of primary somnambulism persisting since childhood. The episodes, which occurred during the first third of the night, were characterized by walking about inside her house and complex behaviors such as cleaning or preparing food. The episodes tended to occur in clusters over several consecutive days every 4 to 8 weeks and were often precipitated by stressful life events or disturbances in her sleep schedule. Her past medical history included bruxism (successfully treated with occlusal splinting) and a tonsillectomy. She also reported a past history of transient panic attacks which had not recurred for several years and did not require treatment. She had no history of RLS or sleep-disordered breathing and reported a positive family history of childhood sleep terrors in her mother. The patient was on no medications other than low-dose estradiol containing oral contraception.

PSG did not reveal sleep-disordered breathing (AHI 0.2 events/h), significant periodic leg movements in sleep (PLMSI 8.3 events/h, 1.6 events/h associated with microarousals) or epileptiform activity. The recording confirmed the absence of significant bruxism with occlusal splinting and an elevated spontaneous microarousal index of 12.6 events/h. However, no behavioral events or awakenings from stage N3 sleep were observed. A subsequent PSG recording undertaken after 24 hours of sleep deprivation revealed 2 episodes of sudden awakenings out of stage N3 sleep during which the patient briefly raises her head, looks around and changes position before falling back asleep.

The patient was initially treated with clonazepam 0.25 mg and showed a partial response over a 6-month period, but continued having 1 to 6 episodes per month. The clonazepam was discontinued and OROS-MPH initiated at 18 mg per day taken in the morning. The patient showed a rapid clinical response within the first week and reported complete resolution of her sleepwalking episodes at follow-up 5 months later. She also spontaneously reported experiencing more restful and refreshing sleep.

Over the next 4 years, the dose was increased twice, to 27 mg then to 36 mg, for relapses during particularly stressful situations (less than twice per year). The patient complained of mild restlessness at the 36 mg dose, which was reduced to 27 mg. The patient attempted discontinuing OROS-MPH 1 year after beginning the medication. This resulted in a re-emergence of frequent, closely-spaced episodes, which remitted once again upon resuming the medication at 27 mg. At last clinical follow-up, 4 years after initiating OROS-MPH, the patient reported continued overall efficacy, with only rare episodes of somniloquy occurring during stressful periods or after missed doses of OROS-MPH.

DISCUSSION

This report presents the cases of two adult patients with primary chronic somnambulism who were successfully treated with OROS-MPH. To our knowledge, this constitutes the first report of OROS-MPH as a treatment for somnambulism. Moreover, the rationale underlying the use of a psychostimulant in the treatment of chronic somnambulism is consistent with our current understanding of this disorder’s pathophysiology.

While somnambulism was traditionally viewed as a disorder of arousal, recent findings suggest that multiple other mechanisms are at play. In addition to abnormal arousal responses, sleepwalkers display intrinsic abnormalities during SWS, including disrupted NREM sleep continuity, diminished slow-wave activity, as well as atypical response to sleep deprivation, resulting in increased SWS fragmentation.⁴ In addition, data from single-photon emission computed tomography and intracerebral EEG studies have revealed the simultaneous presence of sleep state activity in the frontoparietal associative cortex and wakeful activity in the primary motor and cingulate cortices.^5,6 Taken together, these findings have led to the conceptualization of somnambulism as a disorder reflecting the episodic coexistence of processes related to both sleep and wakefulness.^4,7 Moreover, a recent EEG functional connectivity study of sleepwalkers revealed the concomitant presence of arousal and deep sleep processes prior to the onset of sleepwalking episodes.⁸

Within this conceptual framework, one might consider treatment approaches that favor either wakefulness or sleep at the expense of the other, therefore inhibiting the emergence of such hybrid states. The apparent efficacy of clonazepam may thus be partially explained by the promotion of sleep over wakefulness. Similarly, we hypothesize that OROS-MPH pushes sleepwalkers’ underlying sleep-wake dynamics toward wakefulness such that the co-occurrence of sleep and arousal is much less likely during their NREM sleep and the occurrence of potential somnambulistic events gives way to normal awakenings. This hypothesis is supported by the observation that one of our patients noted that her sleepwalking events appeared to be replaced by transient full awakenings in the first third of the night.

Dopamine agonists have been shown to be effective in the treatment of sleep-related eating disorder (SRED), a variant of somnambulism frequently comorbid with RLS and periodic limb movements during sleep and characterized by the ingestion of excessive or unusual food items during episodes.⁹ It is hypothesized that dopamine agonists improve SRED in part by reducing RLS/periodic limb movements during sleep associated arousals. Interestingly, OROS-MPH exerts its mechanism of action by blocking the presynaptic reuptake of dopamine and norepinephrine. Patient one demonstrated occasional eating behaviors during somnambulistic episodes as well as an elevated PLMSI. It is possible that the use of OROS-MPH improved her somnambulism through its dopaminergic action, similar to the mechanism by which dopamine agonists are thought to improve SRED.

An additional potential benefit of OROS-MPH is a reduction in daytime sleepiness. As previously reported, self-reported sleepiness is a frequent complaint among sleepwalkers¹⁰ that is not addressed by clonazepam. Moreover, studies^2,3 have shown that a non-negligible proportion of patients with parasomnias do not respond to clonazepam and that concerns exist with regards to the chronic use of benzodiazepines, including for tolerance, dependence, cognitive impairment and daytime sleepiness.

CONCLUSIONS

In our case report of two adult sleepwalkers, OROS-MPH resulted in a significant improvement in episode frequency and complexity. We suggest that OROS-MPH may be considered as a viable therapeutic option in adult sleepwalkers.

Clinical trials assessing the effect of OROS-MPH on sleep architecture with PSG are warranted. In addition, the assessment of the mechanisms by which OROS-MPH improves chronic somnambulism may further our understanding of the disorder’s pathophysiology.

DISCLOSURE STATEMENT

All authors have read and approved the manuscript. Work for this study was performed at Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur, Montréal, Canada. This research was supported by the Canadian Institutes of Health Research (grant # MOP 49515 to AZ) and by the Fonds de recherche du Québec – Santé to AD. MN, AZ, SB and SG report no conflicts of interest. JM received consultant fees from Canopy Health. AD received research grants from Novartis pharma, Flamel Ireland Limited and Biron as well as honoraria from speaking engagements from UCB. None of the financial disclosures are relevant to the submitted work.

ABBREVIATIONS

AHI

apnea-hypopnea index

EEG

electroencephalography

NREM

non-rapid eye movement sleep

OROS-MPH

osmotic release oral system methylphenidate

PLMSI

periodic leg movements during sleep index

PSG

polysomnography

RLS

restless legs syndrome

SRED

sleep-related eating disorder

SWS

slow-wave sleep