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Protocol
Effectiveness of low-dose amitriptyline and mirtazapine for insomnia disorder: study protocol of a randomised, double-blind, placebo-controlled trial in general practice (the DREAMING study)
  1. Mette H Bakker1,
  2. Jacqueline G Hugtenburg2,
  3. Annemieke van Straten3,
  4. Henriëtte E van der Horst1,
  5. Pauline Slottje1
  1. 1 General Practice, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
  2. 2 Clinical Pharmacology and Pharmacy, Amsterdam UMC Location VUmc, Amsterdam, Netherlands
  3. 3 Clinical Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
  1. Correspondence to Dr Jacqueline G Hugtenburg; jg.hugtenburg{at}amsterdamumc.nl

Abstract

Introduction For over more than a decade, low-dose amitriptyline and mirtazapine are prescribed off-label for insomnia. However, placebo-controlled evidence on these antidepressants for insomnia is still lacking. Therefore, the present trial aims to assess the effectiveness of low-dose amitriptyline (10–20 mg/day) and mirtazapine (7.5–15 mg/day) in patients with insomnia disorder with difficulty maintaining sleep or early-morning awakening problems in general practice.

Methods and analysis The Drug REdiscovery: low-dose Amitriptyline and Mirtazapine for INsomnia disorder in General practice (DREAMING) study is a randomised, double-blind, placebo-controlled trial in about 50 general practices. Adults (18–85 years) with insomnia disorder (Diagnostic and Statistical Manual of Mental Disorders-5) who ask their general practitioner (GP) for sleep medication when non-pharmacological treatment is deemed not effective, are eligible. Exclusion criteria: isolated sleep initiation problem, contraindications for or drug–drug interactions with either amitriptyline or mirtazapine. Participants (n=156) will be randomly assigned to three parallel treatment groups of 16-week treatment with either amitriptyline (one or two tablets of 10 mg/day) or mirtazapine (one or two tablets of 7.5 mg/day) or placebo (one or two tablets) alongside usual GP care. All participants start and end with single dose, but dose can be doubled following GP consultation in week 3. Questionnaire assessments will be conducted at baseline, week 6, 12, 20 and 52. The primary study outcome is self-reported insomnia severity at 6 weeks, measured with the Insomnia Severity Index (ISI) in an intention to treat analysis. Secondary outcomes include subjective sleep quality quantified by sleep indices, daytime functioning and symptoms, safety and treatment evaluation and other sleep care consumption.

Ethics and dissemination The Medical Ethics Committee of the VU Medical Centre Amsterdam approved this trial. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders.

Trial registration number NTR7449.

  • sleep medicine
  • primary care
  • sleep medicine
http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors PS conceived of the study. All authors (MHB, JGH, AvS, HEvdH and PS) contributed to the trial design from a multidisciplinary perspective (respectively general practice, clinical pharmacology and pharmacy, clinical psychology, general practice and epidemiology). MHB drafted the manuscript, is the coordinating researcher and will conduct the statistical analysis. All authors approved the final manuscript.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Provenance and peer review Not commissioned; externally peer reviewed.