The DREAMING study: Efficacy of low dose amitriptyline and mirtazapine for insomnia disorder

The DREAMING study: Efficacy of low dose amitriptyline and mirtazapine for insomnia disorder: a double-blind, randomized, placebo-controlled trial in general practice - DREAMING study

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-003766-27-NL

Enrollment

156

Registered

2018-06-05

Start date

2018-07-18

Completion date

Unknown

Last updated

2022-08-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Insonnia disorder MedDRA version: 20.0 Level: LLT Classification code 10078083 Term: Insomnia disorder System Organ Class: 100000004873

Interventions

Trade Name: amitriptyline Product Name: amitriptyline Pharmaceutical Form: Film-coated tablet Pharmaceutical form of the placebo: Film-coated tablet Route of administration of the placebo: Oral use T

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Adults aged 18-85 years and registered as patient in one of the participating general practices. - Presence of insomnia disorder conform DSM-5, i.e. sleep problems (including problems maintaining sleep) in at least 3 nights a week during at least 3 months, with consequences for daytime functioning. - Request for long-term and/or frequent sleep medication put to their GP because non-pharmacological treatment according to the Dutch (NHG) general practice guideline is deemed insufficient by patient and GP. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 104 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52

Exclusion criteria

Exclusion criteria: General exclusion criteria - Isolated problem falling asleep (without problems maintaining sleep) - Insomnia secondary to another medical condition, e.g. OSAS, comorbid major depression, chronic pain - Habitual shift worker doing night shifts - Wish to continue (over-the-counter) melatonin - Use of off-label amitriptyline or mirtazapine for insomnia in the past year - Terminal illness - Suicide risk - Pregnancy, lactation or wish to become pregnant in the coming 6 months - Vulnerability due to unstable health situation according to GP. - Being unable to follow study instructions and fill out the study questionnaires (in Dutch) - Participation in other interventional medical scientific studies Contra-indications - Allergy for amitriptyline or mirtazapine - Cardiac arrhythmia / blockade / Long QT syndrome / Brugada syndrome / Family history of acute cardiac death - Recent myocardial infarction (within the past 90 days) / Angina pectoris / coronary insufficiency - Severe renal insufficiency (GFR < 10) - Severe liver dysfunction - Epilepsy - Ocular Hypertension / Glaucoma - Bipolar affective disorder - Current alcohol or drug abuse/addiction Potential drug-drug interactions - Current use of psychopharmaceuticals (including anxiolytics as e.g. benzodiazepines, antidepressants including St John’s wort and, anticonvulsants ) - Current use of antimycotics (all types) - Certain enzyme inductors, antiretroviral drugs, cimetidine and clonidine. (All of these are not commonly used and will be excluded by the prescription check by the GP and/or the final check by the pharmacist).

Design outcomes

Primary

Measure	Time frame
Timepoint(s) of evaluation of this end point: baseline, 6 weeks, 12 weeks, 20 weeks and 12 months.;Main Objective: Primary Objective: Our primary objective is to assess the efficacy of a 16-week treatment period of low dose amitriptyline (10-20 mg nightly) or mirtazapine (7.5 – 15 mg nightly) on subjective sleep quality compared to placebo added to usual care in patients with insomnia disorder with sleep maintenance problems in general practice.;Secondary Objective: Secondary objectives are to assess (a) the post-treatment efficacy on subjective sleep quality and sleep indices (up to 12 month), (b) the efficacy regarding daytime symptoms and functioning both during and after treatment (up to 12 months), (c) that the treatment indeed is well tolerated (safe) and (d) whether treatment is sufficient or that additional sleep medication is requested during or after the treatment period (up to 12 months).;Primary end point(s): The primary outcome of the study is the insomnia severity as measured by the Insomnia Severity Index (ISI) (Morin e.a. 2011). The ISI is a 7- item questionnaire scored on a 5-point Likert scale reflecting the severity of both nighttime and daytime aspects of insomnia disorder as perceived by the participant in the last 2 weeks with scores ranging from 0 (no insomnia) to 28 (severe insomnia). The ISI is the recommended outcome measure in insomnia trials (Buysse e.a. 2006). Previous research has indicated that it is a valid and reliable instrument as outcome measurement. It possesses adequate internal consistency and is sensitive to changes in perceived sleep difficulties over time (Bastien e.a. 2001; Morin e.a. 2011). The total score can be interpreted as follows: absence of insomnia (0–7); sub-threshold insomnia (8–14); moderate insomnia (15–21); and severe insomnia (22–28) (Morin e.a. 2011). ISI will be evaluated at each time point: baseline, 6 weeks, 12 weeks, 20 weeks and 12 months.	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: baseline, 6 weeks, 12 weeks, 20 weeks and 12 months.;Main Objective: Primary Objective: Our primary objective is to assess the efficacy of a 16-week treatment period of low dose amitriptyline (10-20 mg nightly) or mirtazapine (7.5 – 15 mg nightly) on subjective sleep quality compared to placebo added to usual care in patients with insomnia disorder with sleep maintenance problems in general practice.;Secondary Objective: Secondary objectives are to assess (a) the post-treatment efficacy on subjective sleep quality and sleep indices (up to 12 month), (b) the efficacy regarding daytime symptoms and functioning both during and after treatment (up to 12 months), (c) that the treatment indeed is well tolerated (safe) and (d) whether treatment is sufficient or that additional sleep medication is requested during or after the treatment period (up to 12 months).;Primary end point(s): The primary outcome of the study is the insomnia severity as measured by the Insomnia Severity Index (ISI) (Morin e.a. 2011). The ISI is a 7- item questionnaire scored on a 5-point Likert scale reflecting the severity of both nighttime and daytime aspects of insomnia disorder as perceived by the participant in the last 2 weeks with scores ranging from 0 (no insomnia) to 28 (severe insomnia). The ISI is the recommended outcome measure in insomnia trials (Buysse e.a. 2006). Previous research has indicated that it is a valid and reliable instrument as outcome measurement. It possesses adequate internal consistency and is sensitive to changes in perceived sleep difficulties over time (Bastien e.a. 2001; Morin e.a. 2011). The total score can be interpreted as follows: absence of insomnia (0–7); sub-threshold insomnia (8–14); moderate insomnia (15–21); and severe insomnia (22–28) (Morin e.a. 2011). ISI will be evaluated at each time point: baseline, 6 weeks, 12 weeks, 20 weeks and 12 months.

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Secondary

Measure	Time frame
Timepoint(s) of evaluation of this end point: baseline, 6 weeks, 12 weeks, 20 weeks and 12 months.;Secondary end point(s): Other sleep parameters A secondary sleep outcome will be sleep quality as measured and quantified according to the Consensus sleep diary (Carney e.a. 2012), minimum version, during one week. The sleep estimates (calculated based on the sleep diary) are amongst others: Sleep Onset Latency (number of minutes to fall asleep after going to bed), Sleep Efficiency (percentage of time slept from the total amount of time spent in bed), Number of Awakenings, Wake After Sleep Onset (total minutes awake after sleep onset), Total Sleep Time and Sleep Quality (a number between 1 and 5 for each night). The Dutch translation of the consensus sleep diary of Carney and colleagues (2012) with some minor consensus adaptations achieved by co Dutch group of sleep researchers (a.o. prof. Dr. A. Van Straten) will be used. Participants will keep the sleep diary prospectively for one week at baseline (before the start of the trial medication), one week during the intervention (week 6) and for one week after the intervention (week 20). In addition to these sleep estimates based on week dairies, participants will be asked to recall their sleep over the past two weeks (i.e. referring to the same time period as the other questionnaires) by means of items 1-4 of the Pittsburgh Sleep Quality Index (PSQI) (Buysse e.a. 1989; Backhaus e.a 2002) at each measurement time point, i.e. to estimate Sleep Onset Latency, Total Sleep Time, Sleep Efficiency, and the number of nights per week in which the participant experienced sleep problems. Finally, a global rate of change (sleep problem compared to baseline) is assessed at 6, 12, and 20 weeks. Daytime functioning related to insomnia The impact of insomnia on daytime functioning will be measured using the Work and Social Adjustment Scale (WSAS) (Mundt e.a. 2002). The WSAS is a 5-item questionnaire on a 8-poin	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: baseline, 6 weeks, 12 weeks, 20 weeks and 12 months.;Secondary end point(s): Other sleep parameters A secondary sleep outcome will be sleep quality as measured and quantified according to the Consensus sleep diary (Carney e.a. 2012), minimum version, during one week. The sleep estimates (calculated based on the sleep diary) are amongst others: Sleep Onset Latency (number of minutes to fall asleep after going to bed), Sleep Efficiency (percentage of time slept from the total amount of time spent in bed), Number of Awakenings, Wake After Sleep Onset (total minutes awake after sleep onset), Total Sleep Time and Sleep Quality (a number between 1 and 5 for each night). The Dutch translation of the consensus sleep diary of Carney and colleagues (2012) with some minor consensus adaptations achieved by co Dutch group of sleep researchers (a.o. prof. Dr. A. Van Straten) will be used. Participants will keep the sleep diary prospectively for one week at baseline (before the start of the trial medication), one week during the intervention (week 6) and for one week after the intervention (week 20). In addition to these sleep estimates based on week dairies, participants will be asked to recall their sleep over the past two weeks (i.e. referring to the same time period as the other questionnaires) by means of items 1-4 of the Pittsburgh Sleep Quality Index (PSQI) (Buysse e.a. 1989; Backhaus e.a 2002) at each measurement time point, i.e. to estimate Sleep Onset Latency, Total Sleep Time, Sleep Efficiency, and the number of nights per week in which the participant experienced sleep problems. Finally, a global rate of change (sleep problem compared to baseline) is assessed at 6, 12, and 20 weeks. Daytime functioning related to insomnia The impact of insomnia on daytime functioning will be measured using the Work and Social Adjustment Scale (WSAS) (Mundt e.a. 2002). The WSAS is a 5-item questionnaire on a 8-poin

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Countries

Netherlands

Contacts

Public ContactDepartment General Practice

VU University Medical Centre

31204448199

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026