Trazodone on NREM Sleep Stage Ⅲ in Depressed Insomniac Co-morbid Patients (n-REMSS)

Impact of Trazodone on Non-rapid Eye Movement Sleep Stage Ⅲ in Depressed Insomniac Co-morbid Patients: a Randomized Controlled Trial

This study used polysomnographic technology and randomly selected 60 patients who met the diagnostic criteria for depression and non-organic insomnia as stipulated in DSM-5 into an intervention group (n=30) and a control group (n=30). The intervention group was given only 5-hydroxytryptamine balanced antidepressants trazodone, while the control group was given citalopram hydrobromide combined with zolpidem. Both groups underwent PSG at baseline and 1 week after medication, and were assessed with the 17-item Hamilton Depression Rating Scale, Zung Self-Rating Depression Scale, Pittsburgh Sleep Quality Index, Arnsworth Insomnia Severity Scale, Antidepressant Side Effects Checklist, and the Drug Dependence Scale neuropsychological assessment at baseline, 1, 2, and 4 weeks after medication. The study aimed to explore the effects of single use of SMAs class antidepressants versus combination with other antidepressants on non-rapid eye movement sleep stage III in patients with depression and insomnia comorbidity, and to compare the effects of depression and insomnia in the two groups.

Study Overview

• Status: Recruiting
• Conditions: Depressed Insomniac Co-morbid Patients
• Intervention / Treatment: Drug: 5-hydroxytryptamine balanced antidepressants trazodone; Drug: Citalopram hydrobromide combined with zolpidem

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Meiling Liu, M.M.; Phone Number: 86+2168306699; Email: tongjie_room@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200124
      • Recruiting
      • Tongji University
      • Contact: Meiling Liu, PhD.; Phone Number: +86-13917639849; Email: tongjie_room@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Outpatient or inpatient patients;
• 18 years old ≤ 65 years old;
• Simultaneously meet the diagnostic criteria for depression and non organic insomnia in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in the United States;
• 17 items of Hamilton Depression Rating Scale (HAMD-17) with a total score of ≥ 17 points;
• Pittsburgh Sleep Quality Index (PSQI) ≥ 16 points;
• Never used related antidepressants and sedative hypnotic drugs;
• Has a certain level of visual and auditory resolution, and no comprehension barriers;
• Capable of independently completing scale measurements;
• Education level above primary school;
• Obtain written informed consent from the patient, and obtain written informed consent from the legal guardian if the patient is incapacitated during the onset of the illness.

Exclusion Criteria:

• Patients with comorbidities such as schizophrenia, schizophrenia, bipolar disorder, mental retardation, pervasive developmental disorder, delirium, dementia, cognitive impairment, alcohol dependence, etc
• Suffering from serious organic diseases, such as diabetes, thyroid disease, hypertension, cardiovascular disease, craniocerebral trauma, cerebral ischemia or hemorrhage;
• Patients with narrow angle glaucoma;
• History of epilepsy and febrile seizures;
• Individuals with a history of drug use;
• Positive for syphilis specific antibody and AIDS antibody;
• According to risk assessment, there are currently serious suicide attempts or individuals who are overly agitated Pregnant or lactating women, or those planning to conceive in the near future;
• Laboratory tests indicate the presence of liver and kidney function impairment in individuals;
• There are other individuals who meet the relevant contraindications for antidepressants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; The intervention group was given only 5-hydroxytryptamine balanced antidepressants trazodone.	Drug: 5-hydroxytryptamine balanced antidepressants trazodone; The intervention group was given only 5-hydroxytryptamine balanced antidepressants trazodone
Active Comparator: Control group; The control group was given citalopram hydrobromide combined with zolpidem.	Drug: Citalopram hydrobromide combined with zolpidem; the control group was given citalopram hydrobromide combined with zolpidem

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep structure staging	Monitoring sleep structure staging through Polysomnography（PSG）: W period (awake period): Refers to the time when one has not entered a sleep state； N1 stage (non rapid eye movement stage 1): light sleep stage, accounting for about 5-10%； N2 stage (non rapid eye movement stage 2): The main part of sleep, accounting for about 50%； N3 stage (non rapid eye movement stage 3): Deep sleep stage, accounting for about 20%, is crucial for memory consolidation and recovery； R phase (rapid eye movement phase): related to dreams, accounting for about 20-25%.	Baseline and 1 week after medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The 17 item Hamilton Depression Scale (HAMD-17)	The 17 item Hamilton Depression Scale (HAMD-17) evaluates the severity of depression and treatment outcomes in patients. Composed of 17 items, ranging from 7 to 13 points, it is classified as mild depression; 14-19 points are classified as moderate depression; ≥ 20 points is classified as severe or above.	baseline, 1, 2, and 4 weeks after medication
Zong's Self rating Depression Scale (SDS)	Zong's Self rating Depression Scale (SDS): It can intuitively reflect the subjective feelings of depressed patients and their symptom changes during treatment. Composed of 20 items, the severity is rated on a 4-point scale from 1 to 4, with 53-62 indicating mild depression, 63-72 indicating moderate depression, and ≥ 72 indicating severe depression.	baseline, 1, 2, and 4 weeks after medication
The Pittsburgh Sleep Quality Index (PSQI)	The Pittsburgh Sleep Quality Index (PSQI) evaluates a patient's sleep quality over the past month, including sleep outcomes and duration. There are a total of 18 items and 7 dimensions, each item is rated on a 4-point scale from 0 to 3. The higher the score, the worse the sleep quality.	baseline, 1, 2, and 4 weeks after medication
The Athens Insomnia Scale (AIS)	The Athens Insomnia Scale (AIS) can be used as a subjective evaluation of insomnia in patients. Composed of 8 items, the severity is evaluated using a 4-point scale from 0 to 3, with a total score range of 0 to 24 points. The higher the score, the worse the sleep quality.	baseline, 1, 2, and 4 weeks after medication
The Antidepressant Side Effect Checklist (ASEC)	The Antidepressant Side Effect Checklist (ASEC) evaluates the adverse reactions of patients after using antidepressants, including physical fatigue, dizziness, headache, sleep disturbances, erectile dysfunction, palpitations, tremors, sweating, dry mouth, constipation, urinary disorders, drowsiness, sexual dysfunction, and other symptoms. Composed of 21 items, the severity is evaluated using a 4-point scale from 0 to 3, with higher scores indicating more severe side effects. evaluates the adverse reactions of patients after using antidepressants, including physical fatigue, dizziness, headache, sleep disturbances, erectile dysfunction, palpitations, tremors, sweating, dry mouth, constipation, urinary disorders, drowsiness, sexual dysfunction, and other symptoms. Composed of 21 items, the severity is evaluated using a 4-point scale from 0 to 3, with higher scores indicating more severe side effects.	baseline, 1, 2, and 4 weeks after medication
Drug Dependence Scale (DDS)	Drug Dependence Scale (DDS) used to identify the degree of drug use dependence. This scale adopts a 4-point rating system, with higher scores indicating higher levels of drug dependence.	baseline, 1, 2, and 4 weeks after medication

Collaborators and Investigators

• Sponsor: Tongji University

Publications and helpful links

General Publications

• Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS; Scientific Advisory Board and the Executive Committee of the Grand Challenges on Global Mental Health; Anderson W, Dhansay MA, Phillips A, Shurin S, Walport M, Ewart W, Savill SJ, Bordin IA, Costello EJ, Durkin M, Fairburn C, Glass RI, Hall W, Huang Y, Hyman SE, Jamison K, Kaaya S, Kapur S, Kleinman A, Ogunniyi A, Otero-Ojeda A, Poo MM, Ravindranath V, Sahakian BJ, Saxena S, Singer PA, Stein DJ. Grand challenges in global mental health. Nature. 2011 Jul 6;475(7354):27-30. doi: 10.1038/475027a. No abstract available.
• Geyer JD, Carney PR, Dillard SC, Davis L, Ward LC. Antidepressant medications, neuroleptics, and prominent eye movements during NREM sleep. J Clin Neurophysiol. 2009 Feb;26(1):39-44. doi: 10.1097/WNP.0b013e318196046f.
• Sheehan DV, Rozova A, Gossen ER, Gibertini M. The efficacy and tolerability of once-daily controlled-release trazodone for depressed mood, anxiety, insomnia, and suicidality in major depressive disorder. Psychopharmacol Bull. 2009;42(4):5-22.
• Sheehan DV, Croft HA, Gossen ER, Levitt RJ, Brulle C, Bouchard S, Rozova A. Extended-release Trazodone in Major Depressive Disorder: A Randomized, Double-blind, Placebo-controlled Study. Psychiatry (Edgmont). 2009 May;6(5):20-33.
• Roth AJ, McCall WV, Liguori A. Cognitive, psychomotor and polysomnographic effects of trazodone in primary insomniacs. J Sleep Res. 2011 Dec;20(4):552-8. doi: 10.1111/j.1365-2869.2011.00928.x. Epub 2011 May 30.
• Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J. [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. Polish.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 11, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 16, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: depression; insomnia; Trazodone; Non-rapid Eye Movement Sleep Stage
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Neurobehavioral Manifestations; Neurocognitive Disorders; Depression; Consciousness Disorders; Sleep Aids, Pharmaceutical; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Central Nervous System Depressants; Neurotransmitter Agents; Membrane Transport Modulators; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Neurotransmitter Uptake Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Parasympatholytics; Serotonin Receptor Agonists; GABA-A Receptor Agonists; GABA Agonists; Zolpidem; Escitalopram; Antidepressive Agents; Serotonin; Citalopram; Dexetimide; Trazodone
• Other Study ID Numbers: PWRq2024-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No