What’s the role of medication for insomnia?
Although the best long term treatments for insomnia are non-drug strategies to change thinking and behaviour around sleep, there is a role for medication. One of the problems though is that there is no perfect medication, and often the effects of medication wear off after a while. So medications are often used to ‘buy time’ to work on other treatments and give people some success with better sleep and allows them to feel better. This in turn puts them in a better position to work on non-drug treatments.
What should I expect from a medication for insomnia?
Unfortunately none of the medications that are available for sleep are perfect, so it’s important to understand the limitations of medications and not expect too much.
The perfect sleeping tablet would:
- Work quickly every time it was taken
- Work for 7-8 hours
- Allow people to wake up feeling refreshed with no carry-over effects
- Have no side-effects
- Maintain it’s effect in the long-term
- Have no potential for addiction or becoming dependent
However, no medications meet all or even most of these criteria. So in choosing a medication it’s important to determine what is important to the individual as different medications have different profiles. For example, some do work quickly, but only last 3-4 hours, whereas others can take longer to work, but last for 5-6 hours.
Research on most common medications used shows that they:
- Shorten the time to get to sleep by 15-30 minutes
- Give people 15-30 minutes more sleep per night
- Reduce the number of awakenings
These results are very different from what is sometimes expected from medications, and highlights that if people rely on medications alone they may be disappointed.
When are medications used?
Short-term use of medications is common in acute (short-term) insomnia. (For an explanation of acute vs chronic insomnia see this post.) In chronic (more than 3 months) insomnia there is not high quality research to guide when to use medication in the treatment of long-term or chronic insomnia. But, research in the last few years suggests that if people are very distressed about their sleep, using medication whilst in parallel working on non-drug treatments gives the best results.
So, my usual practice is to focus on non-drug treatments for insomnia, but if someone is having a lot of trouble and not managing well through the day, to also start a medication. I’ll aim to reduce the medication once people’s symptoms begin to settle as they get more confidence in managing their sleep. That is usually in around 6 weeks to 3 months, but can be longer, particularly if people have either very severe insomnia, other health problems, or a tendency to anxiety which can make insomnia symptoms take longer to settle.
In Australia, the only medication for insomnia approved for use for more than 3 months is suvorexant. This causes problems for people who have insomnia because of chronic health problems as they may need ongoing treatment with medications.
What medications are used?
Rather than using the same medication in each person, I use a range of medication depending on people’s individual circumstances. Some people just have trouble getting to sleep, so will do better with a medication that has a quick onset and doesn’t last for long. Other people wake after 3-4 hours and have trouble in the second half of the night. They need a medication that lasts longer, but this comes with the risk of medication not completely wearing off by the time they need to get up in the morning.
I’ll also try to get an idea of the underlying mechanisms for people’s insomnia. If someone has insomnia because of a body clock problem, then melatonin may be helpful. Whereas if they have trouble switching off, drugs that block alerting neurotransmitters may be more helpful.
So, rather than have a ‘go to’ drug that works for everyone, it’s a matter of matching the medication choice to people’s symptoms and the factors that are contributing to their insomnia.
Benzodiazepines (BDZs): These are the most commonly used and widely known prescription sleeping tablets, and include medications such as:
- temazepam (Temaze, Normison, Temtabs)
- nitrazepam (Alodorm, Modagon)
- oxazepam (Murelax, Serepax)
- flunitrazepam (Hypnodorm)
BDZs are generally quick acting and last around 4 hours, but longer in some people. They can also lose their effect over time in some people leading to increases in the dose or the need to switch to other medications. BDZs work by acting on the GABA receptor and also have some effect on anxiety and cause muscle relaxation. So they can be a good fit if there is insomnia together with anxiety or muscle tension. But can cause problems with sleep apnea where they can worsen relaxation of muscles in the upper airway and make sleep apnea worse.
Benzodiazepine receptor agonists (BDZRAs): These are also commonly used and include:
- zolpidem (Stilnox)
- zolpidem extended release (Stilnox CR)
- zopiclone (Imovane)
BDZRAs are generally quick acting, with zopiclone generally taking a little longer to work, but acting for longer than zolpidem. They appear to have a lower risk of dependence than BDZs, but don’t have the same anti-anxiety effect, as they act more specifically just on the part of the GABA receptor that is involved with sleep. There has been some publicity about zolpidem (Stilnox) and sleep-walking or other unusual behaviours during sleep (parasomnias), but this is something that can be seen with any of the sleeping tablets, so not likely to be just related to Stilnox. Alcohol and stress can increase the risk of sleep walking with any of the sleeping tablets, so it’s important to also manage stress and avoid excessive alcohol when using sleeping tablets.
Because BDZRAs don’t have the same muscle relaxation effects during sleep, I’ll tend to use these more than BDZs in people with sleep apnea.
Melatonin / melatonin receptor agonists: These drugs increase melatonin production, so can be helpful particularly in people who have problems with their body clock that are contributing to their insomnia. Medications are:
- melatonin (Circadin)
- ramelteon (Rozerem – not available in Australia)
Circadin was tested as an insomnia treatment for people over the age of 55 for up to 3 months, so that is how it is recommended for use in Australia. As Circadian is a slow-release formulation of melatonin it is to be taken 1-2 hours before bed. Melatonin’s body clock promoting effects can take 2 weeks to occur, so it’s best suited to staying on it for weeks at a time rather than using on and off when used for long-term symptoms of poor sleep. Melatonin can be used in the short-term for a few days to help reduce symptoms of jet-lag.
Calcium channel alpha-2 delta ligands: Although initially developed as anti-epileptics and now more commonly used for pain, these related drugs have a role in insomnia:
- gabapentin (Neurontin)
- pregabalin (Lyrica)
- gabapentin enacabril (Horizant – not available in Australia)
Gabapentin has been studied in insomnia, with a study that was published in 2014 showing good effects with longer sleep and less time awake during the night.
Dual Orexin Receptor Antagonists (DORAs): A new class of medications for insomnia are drugs that block orexin receptors. Orexin is a key neurotransmitter for promoting wakefulness, so blocking orexin reduces wake drive, allowing sleep to occur. Theoretically this means they may work better for the sort of insomnia where people have trouble switching off. There are a number of these drugs in development,with the only one available for use being:
- suvorexant (Belsomra – approved in Australia, USA and Japan)
Suvorexant has been shown to shorten the time taken to get to sleep and reduce the amount of time spent awake during the night, in 2 randomised controlled trials of 3 months of treatment. The most common side effect was sleepiness, experienced in around 5% of people taking suvorexant. There has also been a studyof people using suvorexant continuously for 1 year showing it was safe and didn’t cause rebound insomnia with stopping the medication or problems with dependence. In Australia the approved starting dose for suvorexant is 20mg, whereas in the US it is 10mg.
Herbs & supplements: People commonly use herbs and supplements purchased over the counter to help with sleep. Common examples include:
- valerian & hops combination (Prosomnia)
- kava kava
The best research data in this area is for valerian with a meta-analysis of a number of individual studies suggesting valerian improves sleep. The combination of valerian and hops marketed in Australia as Prosomnia has also been shown in a number of studies to shorten the time to get to sleep, help people stay asleep and reduce awakenings. Because of the way herbs and supplements work, it can take some time for the full effect to build up, so they’re also better suited to using continuously over a few weeks rather than on and off.
Anti-histamines: These drugs are available over-the-counter and are commonly used by people before seeking advice from health professionals. They include:
- promethazine (Phenergan)
- doxylamine (Restavit)
Although people will commonly trial anti-histamines as they are available without prescription they have a number of problems. They are generally long-acting so can cause carry-over sedation. They also have anti-cholinergic effects which have recently been linked to a risk of developing dementia. I also find that people often become tolerant to anti-histamines quite quickly, so the effect wears off after a couple of weeks.
There are many sub-types of histamine, and this is an active area of research. It’s highly likely that in the future there will be anti-histamines that more selectively block the histamine sub-type involved with alertness and provide a ‘cleaner’ effect with fewer side effects.
Antidepressants: Some anti-depressants are used to help with sleep, they include:
- amitriptyline (Endep)
- dothiepin (Dothep)
- nortriptyline (Allegron)
- mirtazepine (Avanza)
- agomelatine (Valdoxan)
Most modern anti-depressants don’t do much for sleep, and can actually make insomnia or sleep worse for the first few weeks. So while they have a very important role in managing depression or anxiety that may be occurring together with insomnia, they are rarely used by themselves as an insomnia treatment. However, older antidepressants such as the tricyclics, amitriptyline, dothiepin and nortriptyline have mild sedation as one of their effects, so are often used to help with sleep, particularly when there is also pain. Mirtazepine can be a good fit for some people but tends to cause weight gain and carry over sedation in others. Agomelatine is a newer anti-depressant that also has effects on the melatonin receptor so has positive effects on sleep, particularly for those with associated depression or anxiety.
Atypical anti-psychotics: Although these medications were developed to help treat psychosis, because of their widespread sedative effects, they are sometimes prescribed to help with sleep. Drugs in this group include:
- quetiapine (Seroquel)
- olanzapine (Zyprexa)
Whilst the atypical anti-psychotics can be effective sedatives, they often result in people feeling overly sedated throughout the day. Also, in the longer term they can cause significant weight gain and have metabolic effects that can increase the risk of diabetes and cardiovascular disease.