Treating insomnia with medication can be a fine balancing act. Many doctors are reluctant to prescribe sleeping tablets because of concerns that they can lead to problems with addiction and tolerance.
So, instead, GPs tend to opt for using other drugs which have sedative side-effects. These drugs are used ‘off label’ meaning that they are given for a condition for which they are not licensed, in order to try and treat insomnia.
One of the drugs commonly used in this way is mirtazapine. In the UK, mirtazapine is licensed for the treatment of major depression (https://bnf.nice.org.uk/drug/mirtazapine.html).
Mirtazapine was developed by the Dutch pharmaceutical company Organon and was first approved for its use in major depressive disorder in the Netherlands in 1994. It was launched in the United States in 1996 under the brand name Remeron. Mirtazapine is still branded as Remeron in most countries but, as it is no longer patented, generic versions are sold under various brand names around the world.
Mirtazapine, like many other antidepressants, works by increasing the concentration of certain neurotransmitters (chemical messengers) in the brain but differs to many others on the market in just how it does that. Mirtazapine doesn’t stop the recycling of these messengers, but instead blocks some of the receptors they interact with.
There’s some evidence that mirtazapine can be an effective treatment for insomnia in people suffering from depression, but it’s not clear whether it is the drug itself which reduces the symptoms of insomnia, or whether, by reducing the severity of depressive symptoms, it has a knock-on effect of helping the person to sleep better 1.
Mirtazapine has been found to reduce the time it takes for a person to fall asleep, as well as reducing the duration of early, light stages of sleep and increasing deep sleep 2.
It also slightly reduces REM sleep (dream sleep) and night-time waking and improves the continuity and overall quality of sleep 3.
If you want to know more about the phases of sleep, have a look at our article on sleep and its importance, here.
So while it may seem like off-label use of mirtazapine could help with insomnia, it is not without its side-effects.
People with sleeping issues often turn to medication first. Many people don’t know that there are more effective treatments without side effects. Sleepstation’s online CBTi programme can significantly improve sleep in just four sessions.
Interestingly, one of the common side effects of mirtazapine is ‘sleep disorders’, and it may also increase the occurrence of Restless Legs Syndrome and periodic limb movements 4.
Weight gain is also reported as a side-effect, with a study on healthy males concluding that the drug may change the user’s metabolism slightly and increase cravings for sweet foods 5.
Due to its sedating effects, mirtazapine can lead to daytime drowsiness. It can also leave some people feeling groggy or feeling like they have a slight hangover, so following the prescribed dosage is very important.
One such study simulated insomnia by subjecting participants to traffic noise and found that low-dose mirtzapine (7mg) improved both their sleep time and sleep quality considerably, compared to placebo 8.
While looking at the effects of the drug in healthy volunteers is helpful, it is possible that effects may differ between healthy people and those with insomnia.
Studies have looked at the use of mirtazapine in people suffering from depression but, to date, only one study has examined the use of this drug in patients already suffering with insomnia, without depression. The researchers looks at two groups of people: those with both depression and insomnia, and those with only insomnia.
The authors found that low-dose mirtazapine was effective for treating insomnia in both groups, whether the patients also had depression or not 9.
While these results are encouraging, there is still a pressing need to carry out more studies in people suffering with insomnia, to establish if there are any adverse effects from the long-term use of mirtazapine 10.
Gandotra, K., Chen, P., Jaskiw, G.E., Konicki, P.E. and Strohl, K.P., 2018. Effective treatment of insomnia with mirtazapine attenuates concomitant suicidal ideation. J. Clin. Sleep Med., 14(5), pp.901-902.↑
Winokur A, Sateia MJ, Hayes JB, Bayles-Dazet W, MacDonald MM, Gary KA. 2000. Acute effects of mirtazapine on sleep continuity and sleep architecture in depressed patients: a pilot study. Biol. Psych. Jul 1;48(1):75-8↑
Leonard, S.D. and Arun Karlamangla, A., 2015. Dose-Dependent Sedating and Stimulating Effects of Mirtazapine. Proc. UCLA Health, 19: 1– 2.↑
Kolla, B.P., Mansukhani, M.P. and Bostwick, J.M., 2018. The influence of antidepressants on restless legs syndrome and periodic limb movements: A systematic review. Sleep med. rev., 38, pp.131-140.↑
Hennings JM, Heel S, Lechner K, Uhr M, Dose T, Schaaf L, Holsboer F, Lucae S, Fulda S, Kloiber S., 2019. Effect of mirtazapine on metabolism and energy substrate partitioning in healthy men. JCI Insight. Jan 10;4(1). pii: 123786.↑
Ruigt, G.S.F., Kemp, B., Groenhout, C.M. and Kamphuisen, H.A.C., 1990. Effect of the antidepressant Org 3770 on human sleep. Eur. J Clin. Pharmacol., 38(6), pp.551-554.↑
Aslan, S., Isik, E. and Cosar, B., 2002. The effects of mirtazapine on sleep: a placebo controlled, double-blind study in young healthy volunteers. Sleep, 25(6), pp.666-668.↑
Karsten, J., Hagenauw, L.A., Kamphuis, J. and Lancel, M., 2017. Low doses of mirtazapine or quetiapine for transient insomnia: a randomised, double-blind, cross-over, placebo-controlled trial. J. Psychopharmacol., 31(3), pp.327-337.↑
Savarese M, Carnicelli M, Cardinali V, Mogavero MP, Federico F., 2015. Subjective hypnotic efficacy of Trazodone and Mirtazapine in patients with chronic insomnia: a retrospective, comparative study. Arch Ital. Biol. Jun-Sep;153(2-3):231-8.↑
Kamphuis, J., Taxis, K., Schuiling-Veninga, C.C., Bruggeman, R. and Lancel, M., 2015. Off-label prescriptions of low-dose quetiapine and mirtazapine for insomnia in The Netherlands. J. Clin. Psychopharmacol., 35(4), pp.468-470.↑