Clinical management
Amitriptyline and mirtazapine for sleep - what's the evidence?
Amitriptyline and mirtazapine are often prescribed off-label for insomnia.
A double-blind, randomised, placebo-controlled trial recruited 80 adults with insomnia, for whom non-pharmacological treatment was insufficient. They were randomised to mirtazapine (7.5-15mg/day), amitriptyline (10-20mg/day) or placebo for 16 weeks.
The Insomnia Severity Index (ISI) score was assessed at regular intervals (baseline, 6, 12, 20, 52 weeks), with clinically relevant 'improvement' being >7 points lower than baseline and 'recovery', a total score ≤10.
Mirtazapine and amitriptyline led to statistically significantly lower ISI scores compared to placebo at 6 weeks (mean difference -6.0 points, 95% confidence interval -9.0 to -3.1; and -3.4 points, -6.3 to -0.4, respectively), but not at later time points. The reduction in ISI scores was only clinically relevant with mirtazapine, not amitriptyline, at 6 weeks.
WiseGP Action
Where possible, consider a non-pharmacological, whole-person centred approach to insomnia. Read more in our WiseGP Newsletter on this topic: https://www.wisegp.co.uk/newsletter/insomnia-insights
If considering an off-label prescription for insomnia, mirtazapine could have a more clinically relevant impact than amitriptyline. A short course would be preferable due to there being no statistically significant effect compared to placebo on ISI scores when measured beyond 6 weeks.
Read about the research informing this GEM: https://pubmed.ncbi.nlm.nih.gov/39814428/#:~:text=Conclusion%3A%20Compared%20to%20placebo%20low,which%20was%20not%20clinically%20relevant
Promoting CBT-I for insomnia
Cognitive behavioural therapy for insomnia (CBT-I) is underutilised in general practice.
An Australian qualitative study explored factors influencing participants’ intention to engage with psychological interventions (PIs) for insomnia. 20 adults participated in an interview.
Family/ friends positively supported engagement with PIs for insomnia. Hesitance by GPs to prescribe medication prompted some to explore PIs as an alternative. Some perceived GPs to lack confidence and/ or knowledge in PIs for insomnia to actively promote them.
WiseGP Approach
Reflect on how well you explain different psychological interventions- do your patients understand how therapies go beyond the support a relative or trusted friend might offer?
Read about what CBT-I involves, so you are able to explain more about this approach to support engagement. Here’s a useful link: https://www.sleepfoundation.org/insomnia/treatment/cognitive-behavioral-therapy-insomnia
Read about the research informing this GEM here: https://bjgp.org/content/74/745/e560
