Here, MAO inhibitors (ATC code: N06AF*) and several antidepressants (amitriptyline, ATC: N06AA09 imipramine, ATC: N06AA02 desipramine, ATC: N06AA01 doxepine, ATC: N06AA12 nortriptyline, ATC: N06AA10 opipramol, ATC: N06AA05 trimipramine, ATC: N06AA06) were not considered as narcolepsy-related. To account for any uncertainty resulting from this assumption, a sensitivity analysis with a more restrictive definition of “narcolepsy medication” was performed. Since several antidepressants were included in the base definition of narcolepsy-related medications for sample selection, the patients who received an antidepressant during the 12 months preceding the index date (which may have been prescribed to treat a psychiatric condition) were not considered treatment-naïve. Based on a guideline and clinical expert review, the following medications were considered as narcolepsy-specific: nervous system drugs (sodium oxybate, ATC code: N07XX04 pitolisant, ATC: N07XX11), psychostimulants (modafinil, ATC: N06BA07 methylphenidate, ATC: N06BA04 dextroamphetamine, ATC: N06BA02), tricyclic antidepressants (amitriptyline, ATC: N06AA09 imipramine, ATC: N06AA02 desipramine, ATC: N06AA01 doxepine, ATC: N06AA12 clomipramine, ATC: N06AA04 nortriptyline, ATC: N06AA10 opipramol, ATC: N06AA05 trimipramine, ATC: N06AA06), other antidepressants (fluoxetine, ATC: N06AB03 citalopram, ATC: N06AB04 venlafaxine, ATC: N06AX16 reboxetine, ATC: N06AX18 non-selective MAO inhibitors, ATC: N06AF*), benzodiazepines (ATC: N05BA*), and other agents (selegiline, ATC: N04BD01 ephedrine, ATC: R03CA02 lithium, ATC: N05AN01). Sample 3 (treatment-naïve) started their first narcolepsy-specific pharmacological therapy between Jand June 30, 2017, and had not received any narcolepsy-specific medication for at least 12 months earlier. Sample 2 (narcolepsy incident) received their first narcolepsy diagnoses between Jand June 30, 2017, without any previous narcolepsy diagnosis since July 1, 2013. As the management of long-term narcolepsy requires regular evaluation and may include frequent drug switching, dose adjustments, and combination therapies, it poses a challenge to treating physicians. Generally, guidelines recommend that pharmacological treatment decisions should be based on clinical considerations, including the type of narcolepsy, comorbid conditions, and specific patient needs. Benzodiazepines may be used to treat other symptoms of narcolepsy, including hallucinations and fragmented sleep. Ephedrine, dextroamphetamine, and monoamine oxidase (MAO) inhibitors are recommended as second-line therapy for EDS. Additionally, it is known that several antidepressants may be prescribed off-label to treat cataplexy examples include venlafaxine, fluoxetine, reboxetine, and citalopram. Pitolisant is approved for both NT1 and NT2 conditions. The psychostimulants modafinil, methylphenidate, and, recently, solriamfetol are approved medications for EDS in Germany, while sodium oxybate and the antidepressant clomipramine are approved for the treatment of narcolepsy with the NT1. The majority of patients additionally require pharmacological treatment to manage the main symptoms of narcolepsy. Adjustments in behavior and lifestyle include regular sleep schedules, scheduled daytime naps, dietary changes, and preventing sleep deprivation. Treatment for narcolepsy consists of pharmacological therapies as well as behavioral and lifestyle changes.
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