No registrations found.
ID
Source
Brief title
Health condition
Insomnia disorder
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of the study will be 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 in screening as well 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). We use a community sample cut-off score of ≥10 to define clinical insomnia.
Treatment responders are defined as ≥8 point reduction on ISI (Morin e.a. 2011). A relapse is defined as a drawback to ≤8 points to the baseline score of the Insomnia Severity Index measured during follow up at two subsequent measurements. Insomnia severity will be evaluated at baseline, 6 weeks, 12 weeks, and for the responders (until relapse) 2 months after treatment, 4 months after treatment, 6 months after treatment, 8 months after treatment, 10 months after treatment and 12 months after treatment.
Secondary outcome
Secondary outcomes are sleep quality (Sleep Efficiency measures with a sleep diary), daytime symptoms (fatigue (CIS-20), emotional complaints (HADS), physical functioning (subscale SF-36), impairment of functioning (WSAS)).
Possible moderators are baseline characteristics, assessed in the baseline questionnaire (i.e. sex, age, body length and weight, marital status, highest attained educational level, current work status, smoking status, alcohol consumption, duration of insomnia), treatment preference (TPP), pain (subscale SF-36), type of insomnia (ITQ) and causual attributions (CAM-I).
Possible mediators are dysfunctional attitudes and beliefs about sleep (DABS) and sleep related arousal (PSAQ). In the CBT-I condition adherence to CBT-I is assessed .In the medication condition, adherence to medication (MARS-5 and pill count) and withdrawal (DESS), in both conditions side effects are assessed (ASEC, ESS).
Background summary
Insomnia is common in people with medical conditions. Insomnia is related to increased mortality and morbidity. Cognitive behavioral therapy for insomnia (CBT-I) is first choice of treatment and also effective for people with insomnia and medical conditions. Despite the evidence that CBT-I is an effective intervention, there can be limitations to CBT-I for patients with medical conditions, requiring a safe alternative. Preliminary evidence and clinical experience suggests that off-label low dose use of sedating antidepressants such as amitriptyline (AM), might be non-addictive, effective, and well-tolerated alternative to treat insomnia in patients with medical comorbidity. This study aims to investigate whether low dose amitriptyline (10- 20 mg nightly) in patients with chronic insomnia coexisting with medical conditions is as effective as CBT-I in improving subjective sleep.
Study objective
The efficacy of low dose amitriptyline on insomnia is equivalent to first choice treatment CBT-I.
Study design
Primary outcome (ISI): For all participants: baseline, 6 and 12 weeks and further for the responders 2,4,6,8,10 and 12 months post treatment
Secondary outcomes: Sleepdiary at baseline, 6, 12 weeks and 12 months post treatment, CIS-20, HADS, subscale SF-36 and WSAS at baseline, 12 weeks and 12 months post treatment
Moderators (baseline characteristics, TPP, subscale pain SF-36, ITQ and CAM-I) at baseline
Mediators (DBAS, PSAQ) at baseline, 3 and 12 weeks
Adherence in CBT-I group at 6 weeks and at 12 weeks in AM group
Side effects (ESS and ASEC) at baseline, 6 and 12 weeks
Withdrawal (in AM group, DESS) at 14 weeks
Intervention
The treatment consists of 1) 12 weeks one or two units (tablets) of amitriptyline (10 mg) [AM] per night, or 2) CBT-I. During AM treatment, start one unit of Amitriptyline (10mg), patients visit their neurologists at 6 weeks to evaluate their sleep and treatment satisfaction, patients can double their dosage themselves at three weeks (patient can report this at visit to the neurologist at 6 weeks) and stop treatment at 12 weeks. A visit to a specialized nurse will take place at 12 weeks to guide treatment stop.
The CBT-I treatment, a multicomponent intervention, based on the Dutch treatment protocol of Verbeek and van de Laar (2014) will be administered as a standardized 6 weekly group sessions (75 minutes/session) and one follow up session after 6 weeks. Major intervention components include sleep restriction therapy, stimulus control therapy, cognitive therapy for insomnia, relaxation therapy and sleep (hygiene) education.
Inclusion criteria
- Adults aged 18 – 85 years visiting the outpatient clinic department of neurology.
- Presence of insomnia disorder conform DSM-5, i.e. sleep problems in at least 3 nights a week, for at least 3 months with consequences for daytime functioning, the sleep problem cannot be better explained by or occurs exclusively during the course of another sleep disorder
- Score of ≥10 on the Insomnia Severity Index (ISI) (Morin e.a. 2011)
- Have a medical condition and / or chronic pain (> 3 months).
Exclusion criteria
Study related exclusion criteria
- Habitual night shift worker
- Untreated sleep related breathing disorder
- Wish to continue over-the-counter sleep aids as melatonin and medicinal cannabis
- Use of off-label amitriptyline for insomnia in the past year
- Being unable to follow study instructions and fill out the study questionnaires (in Dutch)
- A known diagnosis of dementia
- History of delirium
- Pregnancy, lactation or wish to become pregnant in the coming 6 months
- Terminal illness (prognosis < 1 year)
- Suicide risk
- Epilepsy
- Ocular Hypertension / Glaucoma
- The presence of a severe psychiatric disorder not in remission or adequately treated.
- Current alcohol or drug abuse/addiction (benzodiazepine excluded).
- Participation in other interventional medical scientific studies
Potential drug-drug interactions for amitriptyline
- Current use of psychopharmaceuticals other than benzodiazepine (antidepressants:SSRI’s (e.g. bupropion, fluoxetine, paroxetinefluvoxamine), MAOinhibitors, St John’s wort, anticonvulsants (e.g. carbamazepine)
- Current use of antimycotica (e.g. terbinafine)
Contra-indications for amitriptyline following pharmacological guidelines as used in clinical practice.
- Allergy for amitriptyline
- 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
Design
Recruitment
IPD sharing statement
Plan description
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL7971 |
| Other | METC AMC : METC 2019_101 |