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Study Objectives: Severe chronic insomnia is a common sleep disorder that is mostly persistent and needs to be treated. Pharmacologic treatment options and guidelines are sparse, particularly for long-term treatment. Our study aims to investigate a graduated therapy scheme for moderate to severe chronic insomnia in practice, considering the effects on self-reported sleep quality and quality of life., Methods: Patients with moderate to severe chronic insomnia are given appropriate medication according to a graduated therapy scheme, ranging from L-tryptophan (as the first choice, least potent) to Z-drugs and combination therapies (as the last option, most potent). Each step of the graduated therapy scheme was tested for at least 4 weeks. Sleep- and quality of life-related data were collected in questionnaire form (ISI, PSQI, BDI-II, SF-36) at baseline and during the course of the treatment after 1, 3, 6, 9, and 12 months., Results: Of 86 eligible patients, 60.5% started treatment with L-tryptophan and 8.1% with melatonin. After 3 months, 12.5% were still taking L-tryptophan and 12.5% were taking melatonin. There was a significant decrease in mean ISI, PSQI, BDI-II, and SF-36 scores after 3 months of treatment for all patients in the study (n=64). After 6 months, 22.2% were still taking L-tryptophan, melatonin, or agomelatine, and the remainder had switched to more potent drugs such as antidepressants, hypnotics, daridorexant, or combination therapies., Conclusions: A significant number of patients already responded favorably to mild sleep medications, while others demonstrated their need for more potent treatments. Ongoing monitoring will evaluate the long-term effectiveness of both approaches., Clinical Trial Registration: Registy: German Clinical Trials Register; Title: Schlafqualität und Lebensqualität mit einer medikamentösen Langzeittherapie bei moderater bis schwerer Insomnie; Identifier: DRKS00033175; URL: https://drks.de/search/de/trial/DRKS00033175., (© 2024 American Academy of Sleep Medicine.)