Escitalopram for recurrent isolated sleep paralysis.

Recurrent isolated sleep paralysis can be very disturbing and provoke anxiety. The majority of patients can be treated conservatively with cognitive and behavioural therapies. However, some patients may benefit from a pharmacologic intervention. With only scant available evidence, there are currently no standardized pharmacologic treatment recommendations for recurrent isolated sleep paralysis. We report the first two cases of escitalopram used to successfully treat recurrent isolated sleep paralysis. Escitalopram, the most selective of the selective serotonin reuptake inhibitors, generally improves subjective sleep quality, making it an appealing treatment option.

RECURRENT SLEEP PARALYSIS - FEAR OF SLEEPING.

OBJECTIVE: To report a case of recurrent isolated sleep paralysis (RISP), a benign parasomnia with worrisome and frightening sleep paralysis episodes. CASE: description: We describe a case of RISP in a sixteen-year-old girl who seeks medical attention for anxiety symptoms. The sleep paralysis and associated auditory and tactile hallucinations began three years before with worsening in the last year, causing fear of sleeping. The episodes were intensely frightening causing negative impact in patient's sleep, school performance and social function. Medical conditions were excluded, and she started treatment with a selective serotonin reuptake inhibitor with complete resolution of symptoms. COMMENTS: Sleep complaints are often devalued. Therefore, clinicians should actively ask their patients about their sleep during health assessment.

Recurrent sleep paralysis - fear of sleeping / Paralisia do sono recorrente - medo de dormir

ABSTRACT Objective: To report a case of recurrent isolated sleep paralysis (RISP), a benign parasomnia with worrisome and frightening sleep paralysis episodes. Case description: We describe a case of RISP in a sixteen-year-old girl who seeks medical attention for anxiety symptoms. The sleep paralysis and associated auditory and tactile hallucinations began three years before with worsening in the last year, causing fear of sleeping. The episodes were intensely frightening causing negative impact in patient's sleep, school performance and social function. Medical conditions were excluded, and she started treatment with a selective serotonin reuptake inhibitor with complete resolution of symptoms. Comments: Sleep complaints are often devalued. Therefore, clinicians should actively ask their patients about their sleep during health assessment.

RESUMO Objetivo: Relatar um caso de paralisia do sono isolada e recorrente (PSIR), uma parassonia benigna com episódios inquietantes e assustadores de paralisia do sono. Descrição do caso: Descreve-se um caso de PSIR de uma adolescente de dezesseis anos que buscou cuidados médicos devido a sintomas de ansiedade. A paralisia do sono e as alucinações auditivas e táteis associadas haviam começado três anos antes, com agravamento no último ano, causando medo de dormir. Os episódios eram extremamente perturbadores, gerando um impacto negativo no sono, desempenho escolar e vida social da paciente. Condições médicas foram excluídas e começou um tratamento com um inibidor seletivo da recaptação de serotonina, com resolução completa dos sintomas. Comentários: Queixas relacionadas ao sono são frequentemente subvalorizadas. Portanto, os médicos devem perguntar aos seus pacientes sobre problemas relacionados com o sono durante a avaliação clínica.

The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation and a novel therapeutic drug.

Sleep paralysis is a state of involuntary immobility occurring at sleep onset or offset, often accompanied by uncanny "ghost-like" hallucinations and extreme fear reactions. I provide here a neuropharmacological account for these hallucinatory experiences by evoking the role of the serotonin 2A receptor (5-HT2AR). Research has shown that 5-HT2AR activation can induce visual hallucinations, "mystical" subjective states, and out-of-body experiences (OBEs), and modulate fear circuits. Hallucinatory experiences triggered by serotonin-serotonergic ("pseudo") hallucinations, induced by hallucinogenic drugs-tend to be "dream-like" with the experiencer having insight ("meta-awareness") that he is hallucinating, unlike dopaminergic ("psychotic" and "life-like") hallucinations where such insight is lost. Indeed, hallucinatory experiences during sleep paralysis have the classic features of serotonergic hallucinations, and are strikingly similar to perceptual and subjective states induced by hallucinogenic drugs (e.g., lysergic acid diethylamide [LSD] and psilocybin), i.e., they entail visual hallucinations, mystical experiences, OBEs, and extreme fear reactions. I propose a possible mechanism whereby serotonin could be functionally implicated in generating sleep paralysis hallucinations and fear reactions through 5-HT2AR activity. Moreover, I speculate on the role of 5-HT2C receptors vis-à-vis anxiety and panic during sleep paralysis, and the orbitofrontal cortex-rich with 5-HT2A receptors-in influencing visual pathways during sleep paralysis, and, in effect, hallucinations. Finally, I propose, for the first time, a drug to target sleep paralysis hallucinations and fear reactions, namely the selective 5-HT2AR inverse agonist, pimavanserin. This account implicates gene HTR2A on chromosome 13q as the underlying cause of sleep paralysis hallucinations and could be explored using positron emission tomography.

Drugs Used in Parasomnia.

Patient education and behavioral management represent the first treatment approaches to the patient with parasomnia, especially in case of disorders of arousal (DOA). A pharmacologic treatment of DOA may be useful when episodes are frequent and persist despite resolution of predisposing factors, are associated with a high risk of injury, or cause significant impairment, such as excessive sleepiness. Approved drugs for DOA are still lacking. The most commonly used medications are benzodiazepines and antidepressants. The pharmacologic treatment of rapid eye movement sleep behavior disorder is symptomatic, and the most commonly used drugs are clonazepam and melatonin.

Long-term follow-up of patients with narcolepsy-cataplexy treated with sodium oxybate (Xyrem).

OBJECTIVES: The clinical experience with sodium oxybate (Xyrem) in patients with narcolepsy-cataplexy is still limited, especially in children, elderly patients, and patients with concomitant obstructive sleep apnea (OSA). In this report, we describe 4 patients with narcolepsy and refractory cataplexy who were started on sodium oxybate and followed up for approximately 2 years, including an 11-year-old child and an elderly man with severe OSA. METHODS: The sodium oxybate dose was built up gradually until symptoms were controlled, adverse effects appeared, or the maximum nightly dose of 9.0 g was reached. On average, each subject underwent 4 sleep studies during follow-up after starting sodium oxybate. The nightly dose needed to control symptoms ranged from 5.0 to 9.0 g. RESULTS: Cataplexy, sleep paralysis, and sleep-onset hallucinations disappeared in all cases. In addition, daytime sleepiness decreased subjectively according to the Epworth Sleepiness Scale and objectively according to the Multiple Sleep Latency Test. Polysomnography demonstrated clear reductions in sleep latency, arousal index, and stage 1 sleep (N1). Slow-wave sleep (N3) and sleep efficiency increased with sodium oxybate treatment. Interestingly, the 11-year-old child and the elderly man with documented severe OSA on continuous positive airway pressure therapy demonstrated tolerability to sodium oxybate. Adverse effects included nausea, snoring, paresthesia, convulsion, and enuresis. However, all adverse effects disappeared after reduction of the dose. The beneficial effect of sodium oxybate persisted during the follow-up period. CONCLUSION: Sodium oxybate is an effective and well-tolerated medication for patients with refractory cataplexy. However, it requires special monitoring and follow-up by a specialized center. The improvement in clinical symptoms and sleep architecture seems to persist over time.

Emerging treatments for narcolepsy and its related disorders.

IMPORTANCE OF THE FIELD: Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and nocturnal sleep disruption. Non-pharmacological treatments (i.e., behavioral modification) are often helpful for the clinical management of narcoleptic patients. As these symptoms are often disabling, most patients need life-long treatments. Over 90% of diagnosed narcoleptic patients are currently prescribed medications to control their symptoms; however, available treatments are merely symptomatic. AREAS COVERED IN THIS REVIEW: This review presents a description of the clinical symptoms of narcolepsy, followed by a discussion of the state-of-the-art knowledge regarding the disorder and related emerging treatments. In preparing this review, an extensive literature search was conducted using Pubmed. Only selected references from 1970 to 2008 are cited. WHAT THE READER WILL GAIN: This review focuses on emerging treatments for human narcolepsy, and the reader will gain significant knowledge of current and future treatment for this and related disorders. Traditionally, amphetamine-like stimulants (i.e., dopaminergic release enhancers) have been used for clinical management to improve EDS, and tricyclic antidepressants have been used as anticataplectics. However, treatments have recently evolved which utilize better tolerated compounds, such as modafinil (for EDS) and adrenergic/serotonergic selective reuptake inhibitors (as anticataplectics). In addition, night time administration of a short-acting sedative, gamma-hydroxybutyrate, has been used for the treatment for EDS and cataplexy. As a large majority of human narcolepsy is hypocretin peptide deficient, hypocretin replacement therapy may also be a new therapeutic option; yet, this option is still unavailable. In addition to the hypocretin-based therapy, a series of new treatments are currently being tested in animal and/or humans models. These potential options include novel stimulant and anticataplectic drugs as well as immunotherapy, based on current knowledge of the pathophysiology of narcolepsy with cataplexy. TAKE HOME MESSAGE: We expect that more pathophysiology-based treatments, capable of curing and/or preventing narcolepsy and related diseases, will be available in near future. As cases of EDS, associated with other neurological conditions (i.e., symptomatic narcolepsy or narcolepsy due to medical conditions), are often linked with hypocretin deficiency, these novel therapeutic options may also be applied to treatment of these disabling conditions.

Narcolepsy and psychotic states--a case report.

Narcolepsy is characterized by symptoms that include excessive sleepiness during the daytime, cataplexy, hypnagogic hallucinations and sleep paralysis. We present a single unusual case report of a patient who was admitted to a psychiatric facility. A 20-year-old single woman was hospitalized in a general hospital due to involuntary movements in her limbs. Following complaints of continual daily sleepiness and instances of a loss of muscle tone she was referred for sleep assessment. The patient was diagnosed with narcolepsy and cataplexy. Later, due to auditory hallucinations she was referred to a psychiatric hospital. Her reality judgement was poor, with partial insight regarding her illness. The patient was treated with methylphenidate 20 mg/day and antipsychotic medication; risperidone of up to 4 mg/day, and paroxetine 20 mg/day to prevent cataplexy. Following further exacerbation, pharmacotherapy was changed to risperidone 6 mg/day and modafinil 200 mg/day. This treatment led to a significant improvement in her condition. The report presented here suggests that combined treatment with a psycho-stimulant drug, an SSRI in combination with antipsychotic treatment, may be indicated in narcolepsy with cataplexy and vivid psychotic production. Multidisciplinary cooperation of neurologists and psychiatrists enabled this therapy to be administered for the patient's benefit.

[Integrated treatment of the symptoms of narcolepsy-cataplexy syndrome with sodium oxybate]. / Tratamiento integral con oxibato sódico de los síntomas del síndrome narcolepsia-cataplejía.

INTRODUCTION: Treatment of narcolepsy-cataplexy is based on the use of different drugs that either stimulate or modify REM sleep, which makes it possible to improve the symptoms that characterise the disease. AIM: To present the characteristics of sodium oxybate, a new drug that has been approved in the United States and in the European Union for use in treating narcolepsy-cataplexy; the main contribution made by this new agent is the possibility of acting on all the symptoms of the disease at the same time. DEVELOPMENT: In four randomised, double-blind, placebo-controlled studies and with a class A level of evidence, sodium oxybate has proved to be effective in improving the cardinal symptoms of narcolepsy-cataplexy, that is to say, hypersomnia, cataplexy and fragmentation of nocturnal sleep. Treatment was well tolerated and the side effects, consisting mainly of nausea or symptoms related with the nervous system, such as anxiety, depression, confusion or drowsiness, were mild or moderate in most cases and rarely led to the patient's giving up the treatment. The drug has a favourable pharmacokinetic profile, with little potential to interact with other pharmaceuticals. It seems to have a synergic effect with modafinil, boosting its effects in the treatment of excessive sleepiness. Although it is a substance that has been used as a recreational drug, no cases of addiction or drug abuse have been observed in narcoleptic patients treated in a controlled manner. CONCLUSIONS: Sodium oxybate can be considered to be a first-choice drug in the treatment of narcolepsy-cataplexy.

[Sleep and movement disorders]. / Schlaf und Bewegungsstörungen.

The three different states of being (wakefulness, NREM and REM sleep) are associated with profound neurophysiological and neurochemical changes in the brain. These changes explain the existence of movement disorders appearing only or preferentially during sleep, and the effects of sleep on movement disorders. Sleep-related movement disorders are of clinical relevance for multiple reasons: 1) high frequency (e.g. restless legs syndrome (RLS)); 2) diagnostic relevance (e.g. REM sleep behavior disorder (RBD) as first manifestation of Parkinson disorder); 3) diagnostic uncertainty (e.g. parasomnias vs nocturnal epilepsy); 4) association with injuries (e.g. RBD, sleepwalking), sleep disruption/daytime sleepiness (e.g. RLS), and psycho-social burden (e.g. enuresis); 5) requirement of specific treatments (e.g. nocturnal epilepsy, stridor, RBD). This article gives an overview on clinical manifestations, pathophysiology, work-up and treatment of sleep-related movement disorders (e.g. RLS, bruxism), parasomnias (e.g. sleepwalking, RBD), sleep-related epilepsies, and on sleep-associated manifestations of movement disorders (e.g. Parkinson disease, multiple system atrophy).

Relevance of sleep paralysis and hypnic hallucinations to psychiatry.

OBJECTIVE: To describe a patient who presented with psychopathology in the wake of sleep paralysis and hypnopompic hallucinations, and to discuss the importance of these phenomena to psychiatric diagnoses. METHODS: Case report. RESULTS: A 25-year-old black South African woman developed paranoid beliefs and a sad and anxious mood in the wake of her first experience of sleep paralysis and hypnic hallucinations. She had no history of other sleep-related events. Reassurance, explanation of the physiological basis of her experience, and a short course of low-dose diazepam were provided. Her mood and sleep improved promptly and she no longer held paranoid beliefs. She did not experience further episodes of sleep paralysis or hypnic hallucinations and improvement was sustained at 6 months. CONCLUSIONS: It pays to probe for the core experiences or events that patients may be explaining by devising "delusions". Acute, nocturnal-onset, first-time psychopathology warrants inquiry for sleep paralysis and hypnic hallucinations. Sleep-related side-effects of psychotropic medications need to be studied more closely.

Natural history, symptoms and treatment of the narcoleptic syndrome.

This study describes the clinical features, natural history and treatment of 100 patients with narcolepsy. Over half had one or more affected relatives. Symptoms commenced in adolescence or early adult life in most patients, and remissions were uncommon. Narcolepsy occurred several times each day, often in unusual circumstances and sometimes with little warning. The mean total sleep time of narco-leptics was a little over 9 hours in each 24 hour period, as compared with under 8 in normal subjects. Cataplexy occurred in 93 patients, most commonly when subjects were tired. Attacks were similar in nature to physiological weakness with laughter, although other sudden sensory or emotional stimuli did not cause paralysis of voluntary movement nor loss of muscle tone in normal subjects. Half these patients had frequent dreams before the onset of proper sleep, and 62 had sleep paralysis. This was often frightening, with feelings of suffocation, accompanied by dreams, and of uncertain length. A minority of patients with narcolepsy had muscle aches and jerks before sleep, double vision or loss of focus during cataplexy, went sleep-walking by day, and had daytime hallucinations. Amphetamines had been given to 71 patients for periods of up to 33 years with adequate, but rarely complete, control of narcolepsy. Side effects were common and almost half these patients became tolerant, needing higher dosage to control symptoms. Three patients had a cerebrovascular accident whilst taking amphetamines. Imipramine or clomipramine had ben given in combination with amphetamines to 33 patients for periods of up to 6 years with considerable improvement in both cataplexy and sleep paralysis, and few side effects. Sustained or paroxysmal hypertension as a result of amphetamines or combined treatment did not occur.