Wide implications of a trial on pitolisant for cataplexy

Baumann, Christian R.

doi:10.1016/s1474-4422(16)30398-2

Cited by 4 publications

(3 citation statements)

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“… 90 Pitolisant enhances histaminergic transmission via inhibition of presynaptic uptake (inverse histamine H3 receptor agonist effect). 91 It indirectly increases release of dopamine, norepinephrine, and acetylcholine. 92 Anxiety and depression have been observed but not psychosis, 93 , 94 , 95 in limited data.…”

Section: Resultsmentioning

confidence: 99%

Narcolepsy and psychosis: A systematic review

Hanin

Arnulf

Maranci

et al. 2021

Acta Psychiatr Scand

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Objective Narcolepsy is a rare sleep disorder in which psychotic‐like symptoms can present diagnostic and therapeutic challenges. We aimed to review the association between, and medical management of, narcolepsy and psychosis in children and adults. Methods We reviewed the full text of 100 papers from 187 identified by a PubMed search on narcolepsy plus any of these keywords: psychosis , schizophrenia , delusion , side effects , safety , and bipolar disorder . Results Three relevant groups are described. (i) In typical narcolepsy, psychotic‐like symptoms include predominantly visual hallucinations at the sleep‐wake transition (experienced as “not real”) and dissociation because of intrusion of rapid eye movement (REM) sleep phenomena into wakefulness. (ii) Atypical patients (“the psychotic form of narcolepsy”) experience more severe and vivid, apparently REM‐related hallucinations or dream/reality confusions, which patients may rationalize in a delusion‐like way. (iii) Some patients have a comorbid schizophrenia spectrum disorder with psychotic symptoms unrelated to sleep. Psychostimulants used to treat narcolepsy may trigger psychotic symptoms in all three groups. We analyzed 58 published cases from groups 2 and 3 ( n = 17 and 41). Features that were reported significantly more frequently in atypical patients include visual and multimodal hallucinations, sexual and mystical delusions, and false memories. Dual diagnosis patients had more disorganized symptoms and earlier onset of narcolepsy. Conclusion Epidemiological studies tentatively suggest a possible association between narcolepsy and schizophrenia only for very early‐onset cases, which could be related to the partially overlapping neurodevelopmental changes observed in these disorders. We propose a clinical algorithm for the management of cases with psychotic‐like or psychotic features.

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Section: Resultsmentioning

confidence: 99%

Narcolepsy and psychosis: A systematic review

Hanin

Arnulf

Maranci

et al. 2021

Acta Psychiatr Scand

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“…As most narcoleptic patients treated with pitolisant were diagnosed based on the International Classification of Sleep Disorders , second edition criteria,66 the use of more recent and specific criteria should improve the quality of confirmatory studies regarding the effect of pitolisant on cataplexy and EDS 19…”

Section: Pitolisant: Design and Developmentmentioning

confidence: 99%

Profile of pitolisant in the management of narcolepsy: design, development, and place in therapy

Romigi

Vitrani

Giudice

et al. 2018

DDDT

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Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness and rapid eye movement sleep dysregulation, manifesting as cataplexy and sleep paralysis, as well as hypnagogic and hypnopompic hallucinations. Disease onset may occur at any age, although adolescents and young adults are mainly affected. Currently, the diagnosis delay ranges from 8 to 10 years and drug therapy may only attenuate symptoms. Pitolisant is a first-in-class new drug currently authorized by the European Medicines Agency to treat narcolepsy with or without cataplexy in adults and with an expanded evaluation for the treatment of neurologic diseases such as Parkinson’s disease and epilepsy. This article reviews the pharmacokinetic and pharmacodynamic profile of pitolisant, highlighting its effectiveness and safety in patients with narcolepsy. We performed a systematic review of the literature using PubMed, Embase, and Google Scholar. We report on the efficacy and safety data of pitolisant in narcoleptic patients regarding cataplexy episodes and subjective and objective daytime sleepiness. The development program of pitolisant was characterized by eight Phase II/III studies. One proof-of-concept study followed by two pivotal studies, three randomized controlled trials, and two open studies were evaluated. Our review confirmed the effectiveness of pitolisant in treating major clinically relevant narcolepsy symptoms, including cataplexy, as compared to placebo. In addition, pitolisant revealed a safe profile when compared with placebo and active comparators. Headache, insomnia, and nausea were the prominent side effects. Further long-term randomized controlled trials comparing the efficacy of pitolisant with active comparators (ie, modafinil and sodium oxybate) may clarify its real place in therapy and its possible use as a first-line agent on the basis of its safety and tolerability.

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“…Antagonists blocking the H 1 receptor or the H 2 receptor became successful drugs for the treatment of allergic diseases and gastric acid secretion, respectively, and they are still in use today (Thurmond, 2015). The H 3 receptor modulates histamine actions in the brain, and an inverse agonist of this receptor has been approved for the treatment of narcolepsy since 2016 (Baumann, 2017). However, no antagonists of the H 1 , H 2 or H 3 receptors are able to reduce the inflammatory and pruritic symptoms in chronic inflammatory skin diseases like atopic dermatitis (AD) or psoriasis, although it is well known that histamine is elevated in inflamed skin and plays a relevant role in disease pathology (Gutzmer et al ., 2011).…”

Section: Introductionmentioning

confidence: 99%

The role of the histamine H₄ receptor in atopic dermatitis and psoriasis

Schaper‐Gerhardt

Roßbach²,

Nikolouli

et al. 2019

British J Pharmacology

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Atopic dermatitis (AD) and psoriasis are common skin diseases with a high negative impact on patients' quality of life. Both diseases are mediated by a pro‐inflammatory infiltrate consisting of several cell types, such as T‐cells, antigen‐presenting cells and granulocytes and display disturbed keratinocyte differentiation. Given the fact that histamine levels are also highly elevated in inflamed skin, it is likely that histamine plays a relevant role in disease pathology. However, antagonists blocking histamine H1 receptor or H2 receptors are largely ineffective in reducing chronic symptoms in AD and psoriasis. Over the last years, much research has been undertaken to shed light into the mode of action of the most recently discovered histamine H4 receptor. This research has shown that H4 receptor antagonists display antipruritic and anti‐inflammatory effects not only in mouse models but also in first human clinical trials, and therefore, H4 receptors might present a novel therapeutic target. In this review, we summarize the effects of the H4 receptors on different cell types, mouse models and clinical studies in regard to AD and psoriasis respectively. Linked Articles This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc

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Wide implications of a trial on pitolisant for cataplexy

Cited by 4 publications

References 10 publications

Narcolepsy and psychosis: A systematic review

Narcolepsy and psychosis: A systematic review

Profile of pitolisant in the management of narcolepsy: design, development, and place in therapy

The role of the histamine H₄ receptor in atopic dermatitis and psoriasis

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Wide implications of a trial on pitolisant for cataplexy

Cited by 4 publications

References 10 publications

Narcolepsy and psychosis: A systematic review

Narcolepsy and psychosis: A systematic review

Profile of pitolisant in the management of narcolepsy: design, development, and place in therapy

The role of the histamine H4 receptor in atopic dermatitis and psoriasis

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The role of the histamine H₄ receptor in atopic dermatitis and psoriasis