Amitriptyline en mirtazapine bij langdurige slapeloosheid

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 156

Inclusion Criteria

1.Insomnia Disorder, clinical assessment based on the DSM-5 criteria, i.e. a predominant complaint of dissatisfaction with sleep quantity or quality for three or more days a week during more than three months, resulting in significant daytime impairment despite sufficient opportunity to sleep (DSM-5)2.
2.Non-pharmacological treatment according to the Dutch general practice guideline (including sleep hygiene advice and cognitive behavioural approaches) is deemed insufficient by patient and GP.
3.Consultation of the GP for a sleep medication request, other than for occasional incidental nights or specific period (e.g. traveling).
4.Aged between 18 and 85 years.*
5.Enlisted as patient in one of the participating general practices during the treatment and safety monitoring period.

Exclusion Criteria

6.Insomnia secondary to another medical condition, e.g. OSAS, comorbid major depression, chronic pain.
7.Amitriptyline or mirtazapine is contra-indicated or would pose additional risks based on information known to the GP in usual care, i.e.: allergy for amitriptyline or mirtazapine; cardiac arrhythmia/cardiac 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; concurrent alcohol or drug abuse/addiction; suicide risk; vulnerability due to known unstable health situation, according to GP.
8.Pregnancy, lactation or wish to become pregnant in the next 6 months
9.Terminal illness
10.Potential drug-drug interactions: chronic use of psychotropic drugs (including anxiolytics***, antidepressants, antipsychotics, and anticonvulsants and stimulants); concurrent use of oral antimycotics; enzyme inductors, antiretroviral drugs, cimetidine and clonidine.
11.Prescription of amitriptyline or mirtazapine for insomnia in the past year.
12.Being unable to follow study instructions and fill out the study questionnaires (in Dutch).
13.Isolated sleep initiation problem (i.e. without problems maintaining sleep or early-morning awakening problems).****
14.Doing night shifts on a regular basis.
15.Wish to continue (over-the-counter) sleep aids containing melatonin, St John’s worth, cannabis or antihistamines.
16.Concurrent participation in clinical intervention study interfering with the DREAMING intervention and study procedures.

*** Incidental use of BZRAs for sleep in the preceding months is allowed.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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) and is a valid and reliable instrument as an outcome measurement (ref). 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). Insomnia will be evaluated at each time point: baseline, 6 weeks, 12 weeks, 20 weeks and 12 months.

Secondary Outcome Measures

Name	Time	Method
Secondary outcomes include subjective sleep quality quantified by sleep indices (Sleep Diary, PSQI items, Global rate of change), daytime functioning (WSAS, GSII), daytime symptoms as fatigue, (MFI, Flinders Fatigue Scale items), anxiety and depression (HADS). , safety and treatment evaluation (side effects (ASEC), withdrawal symptoms (DESS), treatment satisfaction and adherence (MARS as well as self-composed, study specific questions). Treatment adherence will also be assessed by pill count. Care consumption is based on self-report and medical records in general practice.<br>