352 Chapter 11 and cataplexy but could facilitate easier reimbursement of treatments in some countries. Despite differences in future names, the suggestions from both expert opinion papers [27, 28] align well with the subgroups that were identified by our data-driven approach. Although the increasing scientific evidence supporting the need for change, it is therefore disappointing that the ICSD-3 Text Revision largely maintained previous criteria for narcolepsy type 2 and idiopathic hypersomnia [9]. An editorial response to our study presented in Chapter 9 emphasised the potential of our findings for meaningful reclassification of central disorders of hypersomnolence, particularly in the absence of cataplexy [453]. The editorial also accurately raised the clinical necessity of linking our identified clusters to potential variations in longitudinal treatment effects in future research as the phenotypical differences observed in our clusters may be useful in predicting treatment responses in individuals with central disorders of hypersomnolence. Future treatments of central disorders of hypersomnolence The results in Chapter 10 highlight the potential for opioids as a new treatment option for narcolepsy type 1. A double-blind randomized controlled trial would be the necessary next step to justify possible implementation in treatment guidelines. Respondents reported the strongest effects with oxycodone, and we therefore recommend testing oxycodone in a future trial. With rising opioid dependence globally [454], caution is warranted before structurally administering opioids to individuals with narcolepsy type 1. Despite the clinical impression that individuals with hypocretin-deficient narcolepsy type 1 are less susceptible to drug abuse and addiction, careful monitoring plans should be put in place to prevent development of substance dependence or abuse of opioids. The treatment landscape of central disorders of hypersomnolence is expected to drastically change with the introduction of hypocretin agonists [455]. With multiple trials rapidly progressing, preclinical and the first clinical results on hypocretin agonists show a striking cessation of excessive daytime sleepiness and cataplexy. Safety profiles of hypocretin-2 agonists should, however, be closely monitored as the first clinical trial had to be prematurely terminated because of clinically relevant elevations in liver-enzyme levels [456]. In the upcoming years, results of other phase II clinical trials are expected [455]. Whether hypocretin agonists may also provide symptom relief in people with narcolepsy type 2 and idiopathic hypersomnia requires further investigation.
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