Effect of graduated drug therapy for moderate-to-severe chronic insomnia on the severity of disease: an observational study in Germany.

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 aimed 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 were 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. Data related to sleep and quality of life were collected in questionnaire form (Insomnia Severity Index, Pittsburgh Sleep Quality Index, Beck Depression Inventory, second edition, and Short Form 36 Health Survey) 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 Insomnia Severity Index, Pittsburgh Sleep Quality Index, Beck Depression Inventory, second edition, and Short Form 36 Health Survey 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, whereas others demonstrated a need for more potent treatments. Ongoing monitoring will evaluate the long-term effectiveness of both approaches.

Clinical trial registration: Registry: German Clinical Trials Register; Name: Schlafqualität und Lebensqualität mit einer medikamentösen Langzeittherapie bei moderater bis schwerer Insomnie; URL: https://drks.de/search/de/trial/DRKS00033175; Identifier: DRKS00033175.

Citation: Boer J, Toncar T, Stange A, Rosenblum L, Fietze I. Effect of graduated drug therapy for moderate-to-severe chronic insomnia on the severity of disease: an observational study in Germany. J Clin Sleep Med. 2025;21(1):33-45.